Localized bullous pemphigoid induced by photodynamic therapy.

Topical photodynamic therapy (PDT) causes localized phototoxicity and has been shown both in vitro and in humans to have immunomodulatory and immunosuppressive effects. We report a case of localized bullous pemphigoid (BP) developing after PDT. Although BP has been reported to develop following cutaneous insults such as surgery, radiotherapy, psoralen ultraviolet A (PUVA) and ultraviolet B phototherapy, PDT has not previously been reported as a trigger. Possible mechanisms include direct mechanical injury to the basement membrane and subsequent autoantibody formation, an indirect immunomodulatory effect of PDT, or most likely, precipitation of BP in individuals with pre-existing low titres of epidermal autoantibodies (so-called subclinical BP). PDT should be added to the list of possible exogenous triggers for BP and this condition should be considered if blistering develops following PDT.

[Relationship between electroacupuncture-induced regulatory effect on leukocytes and the caliber of splenic sinusoid basal lamina eyehole on rabbits].

OBJECTIVE: To study the underlining mechanism of electroacupuncture (EA) in regulating leukocyte counts in the rabbit. METHODS: A total of 75 rabbits were randomly divided into normal control, leukocytosis model, leukocytosis + EA, leukopenia model, leukopenia+EA groups, with 15 cases in each. EA (2-20 Hz, 1-2 mA) was applied to "Dazhui" (DU 14), bilateral "Zusanli" (ST 36) and bilateral "Geshu" (BL 17) for 20 min, once daily for 5 days. Leukocytosis and leukopenia models were duplicated by intravenous injection of coliform (0.1 ml/kg) and cyclophosphamide (30 mg/kg) separately. Peripheral blood leukocyte counts were detected every day. At the end of the experiment, the rabbit's spleen tissue was collected under anesthesia, and the diameter of splenic sinusoid basal lamina eyehole was measured under scanning electronic microscope. RESULTS: Compared with normal control group, after i.v. coliform and cyclophosphamide, leukocytes increased and decreased significantly and respectively, while the area of the splenic sinusoid basal lamina eyehole in leukocytosis model group increased lightly and that of leukopenia model group reduced obviously (P < 0.01). In comparison with their individual model group, the leukocyte count in leukocytosis + EA group decreased considerably (P < 0.05), while that of leukopenia + EA group increased markedly (P < 0.01). The area of splenic sinusoid basal lamina eyehole in leukocytosis+ EA group decreased apparently (P < 0.05), and that in leukopenia+ EA group increased remarkably (P < 0.05). CONCLUSION EA is able to regulate the leukocyte counts in coliform-induced leukocytosis and cyclophosphamide-induced leukopenia rabbits, which may be related with its effects in improving the splenic sinusoid basal lamina eyehole activity.

Quantitative evaluation of effect of renal failure on the pharmacokinetics of panipenem in rats.

The pharmacokinetics of panipenem in experimental renal failure animal models was investigated in order to identify the appropriate covariates affecting the pharmacokinetic behavior. Panipenem and betamipron were administered intravenously to rats with a variety of renal failures, such as nephritis induced by glycerol, gentamicin, uranium and antiserum against glomerular basement membrane as well as 5/6 subtotal nephrectomy. Panipenem in plasma and urine was determined and pharmacokinetic analysis was performed using a one-compartment open model. The elimination half-life prolonged and total body clearance, renal clearance (CL(R)) and renal excretion ratio were decreased according to the renal function, i.e. control>glycerol>anti-GBM=gentamicin>nephrectomy=uranium in order. However, distribution volume was consistent in all models. CL(R) showed strong positive correlation with the glomerular filtration rate in spite of a weak correlation with the reciprocal of blood urea nitrogen. However, no obvious correlation was observed with secretory clearance of N-1-methylnicotinamide. This preliminary information based on animal model might be useful for designing pharmacokinetic studies in special population at early stage of new drug development.

Cicatricial pemphigoid with circulating IgA and IgG autoantibodies to the central portion of the BP180 ectodomain: beneficial effect of adjuvant therapy with high-dose intravenous immunoglobulin.

Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease characterized by deposits of IgG, IgA, or C3 at the cutaneous basement membrane zone. CP may present with considerable variation regarding age, morphology of lesions, and mucosal involvement, which may heal with or without scarring. We describe a patient with CP who presented with circulating IgA and IgG autoantibodies to the epidermal side of salt-split human skin. By immunoblot analysis, the patient's IgA reacted with the soluble ectodomain of BP180 (LAD-1). This reactivity was mainly directed to the central portion of the BP180 ectodomain, a site that, to date, has not been described as the target of IgA autoantibodies. Different immunosuppressive treatment regimens including steroids and mycophenolate mofetil did not control this patient's disease, and severe scarring of the conjunctivae occurred with impairment of vision. Addition of adjuvant intravenous immunoglobulin (1 g/kg body weight on 2 consecutive days) every 4 weeks led to a dramatic improvement of conjunctivitis and gingivitis. Clinical improvement correlated with the serum's IgA immunoblot reactivity against LAD-1. Further studies on a larger number of patients with CP should try to correlate the specificity of autoantibodies in CP with the response to certain therapeutic regimens.

Bullous pemphigoid in a patient treated with UVA-1 phototherapy for disseminated morphea.

Bullous pemphigoid is an autoimmune disease of the skin characterized by the production of antibodies directed at structures of the basement membrane zone (BMZ) leading to subepidermal blisters. Several causative triggers have been described in the literature, among them UV light. Here, we report on a 73-year-old Caucasian female with disseminated morphea who developed blisters on her extremities after receiving whole-body UVA-1 phototherapy. The initial differential diagnosis of a phototoxic versus photoallergic reaction was ruled out as the lesions continued to spread after discontinuation of phototherapy. Histological and direct immunofluorescence examination showing a subepidermal blister and linear IgG deposits along the BMZ along with detection of circulating anti-BMZ antibodies led to the diagnosis of bullous pemphigoid. Immunosuppressive therapy resulted in regression of all blisters. After ruling out other possible causes, such as neoplasias or drugs, we conclude that UVA-1 has to be regarded as the most likely trigger of the disease.

Development and fate of crescentic and granulomatous lesions in rat Masugi nephritis.

It has been observed that with Masugi nephritis in Wistar rats the initiation of endocapillary proliferative changes with macrophage accumulation is usually followed by glomerular sclerosis without extracapillary extension. In the present study, the provocation of an extracapillary lesion was attempted using accelerated Masugi nephritis in Wistar-Kyoto rats. In order to accelerate the accumulation of monocyte/macrophages, the administration of methylcellulose was added in an additional group. The development and fate of extracapillary lesions were analyzed histopathologically and immunohistochemically. As a result, the formation of extracapillary proliferation of granulomatous lesions could be initiated in this model. Granulomatous lesions were composed of CD4+ T cells and CD8+ T cells and monocyte/macrophages including multinucleated giant cells. These inflammatory cells had seemingly escaped from the capillary lumen through the injured glomerular basement membrane and formed cellular and granulomatous crescents. In addition, tenascin was strongly expressed in cellular crescents and was a unique extracellular matrix at this cellular stage. The cellular crescents then progressed to sclerosis with the formation of increased collagenous extracellular matrix. These results suggest that a delayed-type hypersensitivity plays a role in granulomatous crescent formation, even though the initial glomerular injury was evoked by a humoral antibody.

Linear IgA bullous disease limited to the eye: a diagnostic dilemma: response to intravenous immunoglobulin therapy.

PURPOSE: To report on a diagnostic dilemma and treatment challenge in a patient with chronic cicatrizing conjunctivitis without involvement of skin and other mucous membranes persisting for 6 years and not responding to topical and systemic steroids. DESIGN: Interventional case report. METHODS: We performed direct immunofluorescence of the conjunctiva with fluorescein-conjugated rabbit antihuman antibodies against immunoglobulin A, G, and M, complement 3 component, and fibrinogen. To investigate the presence of circulating antibodies in patient's serum, indirect immunofluorescence using normal human conjunctiva, normal human skin, and monkey esophagus as substrate was done. In addition, we did immunoblot analysis using normal human epidermis as substrate to determine the molecular weight of an antigen. The patient was treated with intravenous immunoglobulin (IVIg). The correlation between the titer of circulating antibodies and the activity of conjunctival inflammation at various intervals during the course of IVIg therapy was demonstrated by immunoblot assay with serial dilutions of the patient's serum. The highest dilution at which the binding was visible was considered the titer. RESULTS: Direct immunofluorescence of the conjunctiva and indirect immunofluorescence with both salt split skin and conjunctiva as substrate disclosed linear deposition of immunoglobulin A (IgA) at the epithelial basement membrane. Immunoblot analysis demonstrated the presence of IgA circulating antibodies in patient's serum directed against a 97kDa protein in human epidermis. A continuous decrease in the titer of these antibodies correlating to improvement of clinical symptoms was observed during IVIg therapy. CONCLUSIONS: Use of a nonconventional diagnostic tool (immunoblot analysis), in addition to conventional immunohistologic studies, might be helpful in establishing the diagnosis of patients with chronic cicatrizing conjunctivitis. On the basis of results of these laboratory tests and clinical presentation, we believe that this patient has linear IgA bullous disease limited to the eye. IVIg therapy decreased the titer of circulating antibodies and induced a remission in this patient.

Suppression of experimental autoimmune tubulointerstitial nephritis in BALB/c mice by berberine.

Berberine (BB) is a protoberberine alkaloid derived from various representatives of the Berberidaceae family. Although used as a therapeutic agent, it has not been applied in the treatment of immune-mediated disorders. In the present study, BB was administered at a daily dose of 10 mg/kg for 3 consecutive days before the induction of tubulointerstitial nephritis (TIN) by injection of bovine tubular basement membrane (TBM) antigen in BALB/c mice. The animals were investigated 2 months after TBM inoculation. The intensity of pathological injuries in animals with TIN+BB decreased significantly, an effect that correlated with the improvement of renal function. Flow cytometric analysis of peripheral blood cells showed that BB caused a decrease in the number of CD3(+), CD4(+), CD8(+), and sIg(+) lymphocytes in comparison with TIN mice. The same tendency was noticed in the lymphocytes from kidney infiltrates of treated animals. The control animals treated only with BB showed a decrease in the number of CD3(+), CD4(+), CD8(+) T-lymphocytes in comparison with control nontreated mice. Our results, thus, indicate that BB has an immunosuppressive effect in the TIN model, which is an analogue of various human kidney autoimmune diseases.

Drug-induced linear IgA disease with antibodies to collagen VII.

Linear IgA disease (LAD) is characterized by circulating and tissue-bound IgA antibodies against heterogeneous antigens in the cutaneous basement membrane zone. In most cases the cause is unknown, but a minority of cases has been drug induced. We report a 76-year-old man who developed an acute blistering eruption following high-dose penicillin treatment for pneumococcal septicaemia. Indirect immunofluorescence demonstrated dermal binding IgA antibodies, and Western blotting of serum showed reactivity with a 250 kDa dermal antigen corresponding to collagen VII of anchoring fibrils. Indirect immunoelectron microscopy showed antibody labelling in the lamina densa and sublamina densa zone. This is one of the few cases of drug-induced LAD in which the target antigen profile has been characterized, and the first in which the antigen has been shown to correspond to collagen VII.

Inhibition of inducible nitric oxide synthase intensifies injury and functional deterioration in autoimmune interstitial nephritis.

T lymphocytes are exquisitely sensitive to the antiproliferative effects of nitric oxide. We examined the effects of oral administration of two nitric oxide synthase inhibitors, Nw-nitro-L-arginine methyl ester (L-NAME) and L-N6-(1-iminoethyl)lysine (L-NIL), on the course of T cell-dependent autoimmune interstitial nephritis in Brown Norway rats. Kidneys from rats immunized to produce interstitial nephritis display a net generation of nitric oxide end products. By immunohistochemical staining, the cytokine-inducible nitric oxide synthase (iNOS) is expressed in cortical tubular epithelial cells. Treatment with either inhibitor results in markedly more severe disease following immunization. Animals receiving L-NAME were hypertensive, while those treated with L-NIL, a highly selective inhibitor of iNOS, were not. Evaluation of the expression of IFN-gamma, IL-2, and IL-4 in diseased kidneys by quantitative reverse transcriptase-PCR demonstrated that L-NAME-treated animals displayed significantly augmented levels of IFN-gamma and IL-2 with preserved ratios of IFN-gamma/IL-4 and IL-2/IL-4, while L-NIL-treated animals had augmented levels of IL-2 and IFN-gamma with augmented IFN-gamma/IL-4 and IL-2/IL-4 ratios. Animals treated with L-NAME or L-NIL both had augmented Ag-specific IgG responses. The L-NAME group demonstrated increases in both the IgG2a and IgG1 subtypes, with a constant IgG2a/IgG1 ratio, while the L-NIL group demonstrated an increase in the ratio of the IgG2a/IgG1 response. These Ab and cytokine data suggest that the L-NIL-treated animals had a skewing of their immune response toward a Th1-like response. We conclude that in autoimmune interstitial nephritis, generation of nitric oxide through the iNOS pathway has host-protective effects, and suggest that this may be broadly applicable to T cell-mediated pathologies.

Electron-microscopic and immunohistochemical studies of Langerhans cells and Thy-1-positive cells in mouse tongue epithelium subjected to local hyperthermia.

Local hyperthermia via skin has been used to treat cancer but may suppress local immune responses as a side-effect. To examine effects of heat on immunologically responsive cells in oral mucosa, mouse tongues were heated by an implant system at 43 degrees C for 20 min. The densities of Langerhans cells and Thy-1-positive cells rapidly increased within 3 h after the treatment, then returned to a normal level after 7 days. Electron microscopy confirmed that Langerhans cells in the tongue epithelium formed clusters with lymphocytic cells, suggesting an active response to the hyperthermia.

Multiple autoantibodies in patients with silicone breast implants.

Diverse immunologic abnormalities have been described in women who received silicone breast implants. However, most studies have focused on either a limited number of patients or a small panel of autoantibodies. We report the analysis of 20 autoantibodies in 116 women with implants and 134 controls. The patients ranged from 26- to 66-years-old, with a mean of 45.7 +/- 8.3 years; breast prostheses were in place for a mean of 15 +/- 5.6 years, with a range of 4 to 30, the chief complaints of the 116 patients included polyarthralgias, fatigue, myalgias, morning stiffness, and decreased memory. All 250 sera were tested blindly using a panel of 20 autoantigens including SS-A, SS-B, RNP, cardiolipin (CL), collagen types I, II and IV, phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf), thyroglobulin (TG), gangliosides (GDIa;GM2), proteinase-3 (PR3), Jo-1, Sm, HPRPP-ribosomal phosphate, histones (H2AH2B), Scl-70 and glomerular basement membrane (NC-1). Values from individual patients were considered positive only when greater than 3 SD above the control mean. There was a statistically significant greater frequency of autoantibodies in women with implants for 15 of the 20 autoantigens; these were particularly striking for anti-H2AH2B, HPRPP, SS-A, SS-B, Scl-70, CL, PS, GM2, and NC-1. Many patients harbored several autoantibodies; 20% had four autoantibodies; 8% had six autoantibodies. The association of autoantibodies and implants suggests an adjuvant action of silicon/silicone byproducts.

Cyclosporin A reduces albuminuria in experimental anti-GBM nephritis independently from changes in GFR.

Cyclosporin A (CsA) can reduce proteinuria in various forms of human and experimental glomerulonephritis. This antiproteinuric effect of CsA may be the consequence of diminution of immunological damage, a drug-induced decrease of GFR, or changes in permselectivity of the glomerular basement membrane (GBM). We studied the antiproteinuric effect of CsA in the heterologous phase of a passively induced anti-GBM nephritis in the mouse. This passive model is characterized by acute exudative glomerular lesions and a dose-dependent albuminuria. Rabbit anti-mouse GBM antibodies were administered intravenously in C57B110 mice at day 4, after 3 days of pretreatment with either CsA (75 mg/kg body weight) (n = 15) or olive oil (OO, controls, n = 15) orally. CsA did not influence the severity of the histological lesions. Albuminuria was substantially reduced by CsA (CsA 1.6 +/- 1.8; OO 5.6 +/- 3.2 mg/18 h; P < 0.002). There was a considerable concomitant reduction of the GFR by CsA, as measured with a 51Cr-EDTA single-shot plasma clearance technique before (day-1) and during treatment (day 4): GFR ratio day 4/day-1 for CsA, 0.4 +/- 0.1; for OO controls, 1.1 +/- 0.6; P < 0.01. This drug-induced decrease of GFR was prevented by simultaneous treatment with phenoxybenzamine (PB) twice daily 45 micrograms orally for 4 days (GFR ratio day 4/day-1 for PB and CsA, 0.9 +/- 0.4; controls (PB and OO), 1.0 +/- 0.4; P = NS). Although the CsA-induced GFR reduction was prevented, CsA still reduced albuminuria significantly (PB and CsA, 2.2 +/- 1.8; controls (PB and OO), 5.6 +/- 1.8 mg/18 h; P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

An analysis of 24 patients with IgA deposition at the BMZ.

A study of 24 patients with IgA deposition at the BMZ of the skin showed that five conditions could be recognized: 1) linear IgA bullous dermatosis in adults (LAD, 7 cases); 2) linear IgA and IgG bullous dermatosis in adults (LAGD, 10 cases); 3) chronic bullous disease of childhood (CBDC, 3 cases); 4) dermatitis herpetiformis (DH, 1 case), and 5) systemic lupus erythematosus (SLE, 3 cases). Histopathologically, 5 of 7 patients with LAD were similar to the DH group, but 7 of 10 patients with LAGD were similar to the BP group. Half the patients with LAD and LAGD had oral lesions, and most of them had excellent responses to dapsone and Tripterygium Wilfordii, but the patients with CBDC did not respond to these treatments. In the patients with LAD and LAGD, the positivity rates of IgA anti-BMZ antibodies examined by indirect immunofluorescence (IIF) on intact skin and NaCl split skin were 41% and 64%, respectively. The heterogeneity of the histopathologic pictures of LAD and LAGD, the incidence of DH, and the value of using NaCl split skin for IIF are discussed.

Comparison of converting enzyme inhibitor and calcium channel blocker in SHR with nephrotoxic serum nephritis.

In order to compare the protective effects of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) on the renal function in experimental nephritis, nephrotoxic serum nephritis was induced in male spontaneously hypertensive rats (SHR). The above drugs were then chronically administered to different groups, as follows: the ACEI-treated group (n = 7) received captopril (150 mg/kg/day), and the CCB-treated group (n = 6) was given both nifedipine (40 mg/kg/day) and nisoldipine (20 mg/kg/day). The control group (n = 8) received a placebo. Although the control group developed marked hypertension and proteinuria, the rats treated with either ACEI or CCB demonstrated a significant and equivalent decrease in mean arterial pressure and urinary protein excretion. At 15 weeks after the injection of nephrotoxic serum, all rats were anesthetized with Inactin, and the glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. In the control group, GFR and RPF were markedly attenuated. However, both were preserved at much higher levels in the ACEI-treated group, and GFR was also maintained to a similar degree in the CCB-treated group. Histological studies were carried out after the clearance studies. As a result, it was found that the ACEI treatment significantly limited the development of glomerulosclerosis, whereas CCB modestly ameliorated the glomerular structural lesions. Moreover, ACEI significantly reduced the serum cholesterol, while CCB did not exert such an effect. These results suggest that both ACEI and CCB have a therapeutic effect in experimental glomerulonephritis models which are accompanied by hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine (4): Effects on accelerated passive Heymann nephritis in rats.

We investigated the antinephritic effect of TJ-8014, in comparison to dipyridamole, on accelerated passive Heymann nephritis in rats. TJ-8014 (4.0 g/kg/day, p.o.) given from the heterologous phase (from the day of injection of the antiserum against Fx1A) markedly inhibited the urinary protein excretion and the elevation of plasma cholesterol levels as well as glomerular histopathological changes. When the treatment was started from the autologous phase (from the 22nd day) after proteinuria was fully developed, TJ-8014 also showed a beneficial effect. Dipyridamole (0.4 g/kg/day, p.o.) had no effect when the treatment was started either from the heterologous or autologous phase. TJ-8014 decreased glomerular rat IgG and rat C3 deposits, although it affected neither the plasma antibody titer against rabbit gamma-globulin nor the plasma complement level. TJ-8014 markedly prevented the reduction of plasma and adrenal corticosterone level as well as the reduction of renal blood flow of rats with nephritis. These results suggest that TJ-8014 may be a useful drug against idiopathic membranous nephropathy and the beneficial effect of this drug may be caused by the elimination of glomerular immune deposits and C3 through the increase in renal blood flow related to the enhanced release of adrenal corticosterone.

A fish oil diet preserves renal function in nephrotoxic serum nephritis.

Fish oil diets preserve renal function in murine lupus, but we have found that these diets accelerate renal deterioration in renoprival nephropathy. In this study we examined the effects of dietary fish oil in accelerated nephrotoxic serum nephritis. For 1 month, 14 female rats were fed diets that differed only in fat composition, containing either menhaden (fish) oil or beef tallow (control). Rats were then preimmunized with rabbit IgG and, 5 days later, were injected with nephrotoxic serum. Glomerular filtration rate (GFR) was measured continuously in conscious animals by means of intraperitoneal 14C-labeled inulin minipumps. Fish oil-containing diets markedly attenuated the nephrotoxic serum-induced decline in GFR and the rise in proteinuria and significantly reduced glomerular prostaglandin E2 and thromboxane A2. The results of tests of renal histology showed no differences between the two groups. Five days after preimmunization, rats fed fish oil had more rabbit IgG remaining in their serum and had mounted less of an antibody response to the rabbit IgG. Fish oil diets also resulted in an attenuated disappearance of injected 14C-labeled rabbit IgG. In vitro, peritoneal macrophages from rats fed fish oil took up less rabbit IgG than macrophages from rats fed control diets. Thus the beneficial effects of a fish oil diet may result from defective immune surveillance and from alterations in eicosanoids.

Characterization and quantification of cellular infiltrates in nasal mucosa of patients with grass pollen allergy, non-allergic patients with nasal polyps and controls.

Little is known about cellular infiltrates in nasal mucosa and the differences between these infiltrates in allergic and non-allergic patients. A reproducible and objective method making use of monoclonal antibodies for the quantification and characterization of cellular infiltrates in biopsy specimens of nasal mucosa is described. This method was used to study quantitative differences in cellular infiltrates in the epithelium and lamina propria of the nasal mucosa of patients with isolated grass pollen allergy, non-allergic patients with nasal polyps, and controls. A surprisingly wide variation was found in all groups. In all groups the T lymphocytes were much more numerous than the B lymphocytes. The number of CD8+ cells exceeded the number of CD4+ cells in the epithelium but in the lamina propria the numbers were approximately equal. Significant differences between the three groups were found with respect to the number of CD1+, IgE+, neutrophils and cytoplasmic IgG4+ cells. No significant differences were found in the numbers of CD4+, CD8+, CD14+, CD22+, HLA-DR+, IgG1-3+ cells or eosinophils. The use of biopsy in combination with monoclonal antibodies is an easy and well-tolerated method to study immunological reactions in the nasal mucosa. The results of this study indicate a possible role for a T-cell-mediated response in allergic rhinitis.

Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine, and its mechanisms (2): Effect on the release of corticosterone from adrenal glands.

In order to elucidate the mechanisms of the antinephritic action of TJ-8014, the effect of this drug on corticosterone release from the adrenal cortex was investigated by using normal rats and rats with original-type anti-GBM nephritis. When the serum corticosterone level was determined 5 hr after test drugs were given p.o. to normal rats, TJ-8014 at 0.5 and 2.0 g/kg significantly elevated the hormone level by 48% and 74%, respectively. Of the crude drugs that constitute TJ-8014, Bupleuri radix (SAIKO) and Glycyrrhizae radix (KANZOU) at 1.0 g/kg also significantly elevated the serum level. When TJ-8014 was given p.o. daily from the next day of anti-GBM serum injection to the 15th day, 2.0 g/kg/day of the drug inhibited the urinary protein excretion. In addition, TJ-8014 (2.0 g/kg/day) inhibited the decrease in the serum and adrenal corticosterone levels induced by nephritis. When corticosterone at 10 mg/kg was given s.c. daily from the next day of the anti-serum injection to the 10th day, it not only reduced proteinuria, but also inhibited glomerular histopathological changes. In contrast, metyrapone, a corticosterone synthetase inhibitor, at 100 mg/kg x 2/day, p.o., aggravated the nephritis. These results suggest that the antinephritic action of TJ-8014 may be partly due to the enhancement of the synthesis or release of corticosterone from the adrenal cortex.

Studies on antinephritic effect of TJ-8014, a new Japanese herbal medicine, and its mechanisms (1): Effects on original-type anti-GBM nephritis in rats and platelet aggregation.

In this study, we investigated the antinephritic effects of TJ-8014 and crude drugs in TJ-8014, in comparison to dipyridamole, on original-type anti-GBM nephritis in rats. TJ-8014 (2.0 and 3.0 g/kg/day, p.o., for 12 days) markedly inhibited the urinary protein excretion and the elevation of the plasma urea nitrogen (UN). In addition, TJ-8014 was effective in inhibiting the histopathological changes of hypercellularity and adhesion in glomeruli. Although dipyridamole (0.4 g/kg/day, p.o., for 12 days) had no effect on the plasma UN level, it was as effective as TJ-8014 on the other parameters. When each crude drug which constitutes TJ-8014 was given p.o., daily at 0.2 g/kg, only. Holen was effective in inhibiting the urinary protein excretion as well as histopathological changes. Ginseng radix reduced both the hypercellularity and the adhesion, while Bupleuri radix. Glycyrrhizae radix and Zizyphi fructus reduced only the hypercellularity. TJ-8014 and dipyridamole inhibited the platelet aggregation in normal and nephritic rats. These results indicate that TJ-8014, like dipyridamole, has a beneficial effect on original-type anti-GBM nephritis in rats and the antinephritic action of TJ-8014 may be partly due to the antiplatelet action of this agent.