Low-level laser therapy improves crescentic glomerulonephritis in rats.

Low-level laser therapy (LLLT) can reduce inflammation in a variety of clinical conditions, including trauma, postherpetic neuralgia, and rheumatoid arthritis. However, the effect of LLLT on internal organs has not been elucidated. The goal of the present study was to investigate the anti-inflammatory effect of daily external LLLT in an animal model of crescentic glomerulonephritis. Crescentic glomerulonephritis was induced in male Wister Kyoto rats by intravenous injection of antibody for glomerular basement membrane (GBM). The rats were irradiated with a low-reactive level diode laser with an infrared wavelength of 830 nm from the shaved skin surface once a day for 14 days (irradiation spot size on the skin surface, 2.27 cm(2); power intensity, 880 mW/cm(2); irradiation mode, continuous mode; irradiation time, 250 s; energy, 500 J; energy density, 220 J/cm(2)). After laser irradiation for 14 days, animals were killed, and the extent of inflammation was evaluated. Expression of gene for inflammatory cytokines including interleukin (IL)-1ß and tumor necrosis factor alpha (TNF-α) was assessed by reverse transcription polymerase chain reaction. Crescent formation in glomeruli and infiltration of macrophages and lymphocytes were assessed by histochemical observation. Injection of anti-GBM antibody induced severe glomerulonephritis with crescent formation. Histological observations indicated that LLLT suppressed crescent formation and infiltration of ED1+ macrophages and CD8+ lymphocytes into the glomeruli. LLLT attenuated the levels of IL-1ß and TNF-α messenger RNA in the renal cortex. Externally directed LLLT suppresses the activity of rat anti-GBM crescentic glomerulonephritis in rats. LLLT has the potential to be used for direct treatment of glomerulonephritis.

[Effects of radiotherapy upon progression of crescentic glomerulonephritis in rats].

OBJECTIVE: To study the effects of radiotherapy upon progression of crescentic glomerulonephritis in rats. METHODS: Male SD rats were divided into three groups: (1) control (n=12), sham-operation; (2) crescentic glomerulonephritis (n=23), intravenously inject with nephrotoxic serum (NTS); (3) radiotherapy (n=55), a single low-dose irradiation of 0.5 Gy X-ray to both kidneys at Days 6, 13, 20 and 27 after NTS injection, and sacrificed at different time points among control and crescentic glomerulonephritis rats. Radiotherapy rats have received local kidney irradiation at Days 6, 13, 20 and 27 after bolus NTS injection and would be referred to as NTS7dRa1d, NTS14dRa1d, NTS21dRa1d and NTS28dRa1d, respectively. RESULTS: For NTS7dRa1d and NTS14dRa1d rats of radiotherapy, the levels of serum creatinine, glomerular hypercellularity, crescents and global sclerosis were significantly lower at Days 8 (P < 0.05), 15, and 22 post-irradiation as compared with group of crescentic glomerulonephritis of similar time intervals (P < 0.01). The extent of tubulointerstitial damage was also reduced, and radiotherapy associated histological improvements were accompanied by reduced macrophage infiltration in glomeruli and interstitium. The numbers of PCNA- and ED1-positive cells were reduced in the kidneys at Day 1 postirradiation in NTS7dRa1d and NTS14dRa1d rats as compared with group of crescentic glomerulonephritis at similar time intervals (P < 0.05). A larger number of TUNEL-positive cells were noted at Day 1 postirradiation in rats irradiated at Days 6 & 13 after NTS injection as compared with group of crescentic glomerulonephritis at similar time intervals (P < 0.05). With regards to immunostaining for macrophages ED1 and TUNEL, serial sections of irradiated nephritic kidney showed that fewer ED1-positive macrophages were stained for TUNEL. As evaluated expression of active caspases 3 & 7 was noted in irradiated kidneys as compared with the corresponding group of crescentic glomerulonephritis at similar time intervals. Western blot analysis showed marked increase in the expression of active caspase 3 & 7 in irradiated kidneys as compared with NTS injection only the expression of a marked increase in the expression of p53 protein, closely related to radiation-induced apoptosis, was also observed in irradiated kidneys as compared with NTS injection only. CONCLUSION: Radiotherapy inhibits the progression of experimental crescentic glomerulonephritis through inducing apoptosis by a p53-dependent pathway.

[Conditions contributing to late diagnosis of Wegener's granulomatosis--own experience]. / Uwarunkowania opóznien w rozpoznawaniu ziarniniaka wegenera--doswiadczenia wlasne.

The paper presents two cases of Wegener's granulomatosis, diagnosed in the phase of advanced renal failure, requiring dialysis therapy. Analysis of factors resulting in delayed diagnosis was performed.

[Infrared sweat secretion stimulation as a means of homeostatic correction in patients with kidney dysfunction]. / Infrachervona stymuliatsiia potovydilennia iak zasib korektsiï homeostazysu u osib z porushenniam nirkovoï diial'nosti.

The clinical and laboratory investigation was done on 40 patients with kidney disfunction (glomerulonefritis), treated by standard medicines with regulary infrared total body heating (from 15-20 to 40 min) daily during 10 days. Control group of 37 patients, was treated only by standard medicines. The thermochambers construction forces the possibility of normal temperature air breathing under the radial skin heating to 50-60 degrees C. It was shown, that hypertensions, dropsy manifestation and nitrogen contents in blood significantly decreased in comperison with the control group of patients. The positive effects in laboratory dates was shown in 65%; the subjective reports--in 100% patients. These data may be conformed to widley using infrared chamber procedures for combinative drugs and thermal treating patients with kidney disfunction.

Therapeutic effect of early thymic irradiation in (NZB x NZW)F1 mice, associated with a selective decrease in the levels of IgG3 and gp70-anti-gp70 immune complexes.

The lupus-prone (NZB x NZW)F1 female mice (NZB/W) develop an autoimmune disease characterized by production of autoAb and fatal glomerulonephritis. Since it has been previously shown that total lymphoid irradiation has a beneficial effect in this model, we have analyzed whether early thymic irradiation (ETI) could improve the course of the lupus-like syndrome in these mice. NZB/W mice received thymic irradiation (4500 rads) beginning at 10 weeks of age, prior to the onset of autoimmune manifestations. Then, they were evaluated for survival, renal histology, and serological markers of autoimmunity, in comparison to nonirradiated NZB/W females. The treatment with ETI improved nephritis and survival in NZB/W mice: 50% mortality was observed at 12 months in irradiated mice and at 9 months in untreated mice. This improved survival could not be attributed to a reduction in the titers of anti-dsDNA Ab nor in the levels of total immune complexes which were essentially identical in both groups. By contrast, this improvement was related to a selective normalization in the serum levels of IgG3 and gp70-anti-gp70 immune complexes (gp70IC) in ETI NZB/W female mice as compared to that seen in nonirradiated NZB/W females. These data show the therapeutical effect of ETI and support the pathogenic role of IgG3 and gp70IC in the development of glomerulonephritis in NZB/W mice.

Treatment of intractable lupus nephritis with total lymphoid irradiation.

Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

Immune reactivity and immunosuppressive intervention in experimental nephritis. II. Effect of TLI on the course of two models of nephritis in the inbred rat.

Fractionated high-dose (3400 rad) total lymphoid irradiation (TLI) induces a unique and prolonged state of immunologic unresponsiveness. The therapeutic efficacy of TLI in immune glomerular disease was explored in two animal models: the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN) and autologous immune complex nephritis (AICN). LEW rats with established AA-NTSN, subjected to TLI, manifest decreased levels of circulating antibody to the heterologous (sheep) immunoglobulin G (0.4 +/- 0.2 vs 1.2 +/- 0.3 mg/ml, mean +/- SE respectively, p less than 0.01) early post TLI in association with a reduction in histopathology and albuminuria (6.7 +/- 2.2 vs control 19.6 +/- 5.4 mg/24 hr, mean +/- SE, p less than 0.02). Administration of TLI to rats with established AICN effected significant (p less than 0.001) reduction in albuminuria (162 +/- 30 vs 315 +/- 27), serum creatinine (p less than 0.005), and the incidence of lipemia (p less than 0.01) vs controls. Adoptive transfer studies provided no evidence that the sustained beneficial effect of TLI in AICN was suppressor cell mediated. Thus, the observed therapeutic efficacy of TLI in the treatment of experimental nephritis, shown to be related to a reduction in the level of circulating antibody in AA-NTSN, provides a new model system for study of immunity and immunosuppression in primary glomerular disease.

Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation.

Adult female (NZB/NZW)F1 hybrid mice with documented autoimmune glomerulonephritis resembling systemic lupus erythematosus were treated with fractionated total lymphoid irradiation (TLI), a modification of the radiotherapeutic regimen currently used for the treatment of Hodgkin disease. After TLI, proteinuria subsided in all mice that had undergone radiotherapy, and the mean survival increased from 359 days in untreated controls to 545 days. It is suggested that TLI should be further investigated as a new approach for immunoregulation of autoimmune disorders.

Reversal of nzb/nzw disease with total lymphoid irradiation.

NZB/NZW mice spontaneously exhibit autoimmune disease similar to that seen in human systemic lupus erythematosus (SLE). We demonstrated that total lymphoid irradiation (TLI) reversed well expressed disease in 6-mo-old NZB/NZW females with a prolongation in survival, decrease in proteinuria, and decrease in anti-DNA antibodies as compared to control animals. Few side effects were observed in the treated group. TLI also prolonged survival in animals with advanced renal disease. These findings suggest that TLI may have application to the treatment of human SLE.