Effect of the concentration of phenothiazine photosensitizers in antimicrobial photodynamic therapy on bone loss and the immune inflammatory response of induced periodontitis in rats.

BACKGROUND AND OBJECTIVE: Antimicrobial therapy can suppress periodontal pathogens and increase the effectiveness of conventional mechanical treatment. The aim of this study was to assess bone loss and the immune inflammatory response of rats under the influence of two photosensitizing agents (MB and TBO) at two different concentrations in antimicrobial photodynamic therapy (aPDT), used as an adjuvant therapy in the treatment of periodontitis. MATERIAL AND METHODS: Periodontitis was induced in the mandibular first molars of 162 rats. The animals were divided into nine groups: G1 - scaling and root planing (SRP); G2 - SRP plus 100 µg/mL of methylene blue (MB); G3 - SRP plus 10 mg/mL of MB; G4 - SRP plus 100 µg/mL of toluidine blue (TBO); G5 - SRP plus 10 mg/mL of TBO; G6 - SRP plus 100 µg/mL of MB and laser; G7 - SRP plus 10 mg/mL of MB and laser; G8 - SRP plus 100 µg/mL of TBO and laser; and G9 - SRP plus 10 mg/mL of TBO and laser. Six animals from each group were euthanized 7, 15, or 30 d after treatment. Bone loss (BL) in the furcation region was evaluated using histomorphometric and immunohistochemical analyses to detect the receptor activator of nuclear factor-Κappa B ligand (RANKL), osteoprotegerin (OPG) and tartrate-resistant acid phosphatase (TRAP). RESULTS: There was significantly less BL in animals treated with aPDT using low concentrations of MB and TBO at 7, 15 and 30 d. Immunohistochemical analysis revealed decreased RANKL and increased OPG in the aPDT groups and decreased TRAP-positive cells in G6 and G8. CONCLUSIONS: aPDT, using low concentrations of MB and TBO, was the most effective adjuvant therapy to SRP, acting indirectly as a downregulator of the molecular mechanisms that control bone resorption in periodontitis.

Transduction of thymidine phosphorylase cDNA facilitates efficacy of cytosine deaminase/5-FC gene therapy for malignant brain tumor.

The in vivo gene delivery of E. coli cytosine deaminase (cd) cDNA and systemic 5-fluorocytosine (5-FC) administration have been studied extensively because of their clinical relevance to cancer gene therapy. This approach has the potent advantage of a stronger bystander effect compared to the previous thymidine kinase suicide gene system of the herpes simplex virus. However, 5-fluorouracil (5-FU), an active metabolite in cd with 5-FC therapy, is not always effective for every type of tumor since the enzymes responsible for further drug metabolism vary significantly in each tissue. In this study, we aimed to increase the sensitivity of 5-FU by transduction of thymidine phosphorylase (dThdPase) cDNA into brain tumor cells. After retroviral transfer of the cDNA, we obtained 9L murine gliosarcoma cells showing stable expression of the target enzyme (9L-dThdPase). The growth of the cells was identical to wild type (9L-WT) or control-vector transfected (9L-Neo) cells in vitro. Sensitivity to 5-FU was increased in 9L-dThdPase cells. After the adenoviral delivery of cytosine deaminase gene into these cells, 9L-dThdPase cells also demonstrated an increased sensitivity to 5-FC. Moreover, we showed that transduction of dThdPase cDNA prolongs the survival of animals bearing intracerebral tumors after experimental in vivo cytosine deaminase gene therapy. These results suggest that transduction of thymidine phosphorylase may be a beneficial approach to increasing the efficacy of cd/5-FC suicide gene therapy in certain types of tumor.

[Immunological properties of S-1090, cefmatilen hydrochloride hydrate].

S-1090, a cefmatilen hydrochloride hydrate, is being developed as a cephalosporin antibiotic for oral use. Immunogenicity, hypersensitivity-eliciting antigenicity and immunological cross-reactivity with other antibiotics were evaluated by active systemic anaphylaxis (ASA) test, passive cutaneous anaphylaxis (PCA) test and enzyme-linked immunosorbent assay (ELISA) using guinea pigs and mice/rats. In addition, in vitro direct Coombs' test was also performed to examine the possibility of hemolytic anemia in clinical use. Immunogenicity of S-1090 was not observed in guinea pigs after repeated immunization with S-1090 by ASA or PCA tests. Even in ELISA, only weak antibody production against S-1090 was found in some guinea pigs from the intraperitoneal groups showing the antibody titers only 10(1) to 10(2). When the sera collected from C3H/He mice and C57BL/6J mice immunized with S-1090 were tested for immunogenicity, rat PCA was elicited in a C3H/He mouse serum by S-1090 and antibodies against S-1090 were detected in a C57BL/6J mouse serum by ELISA. When adjuvant was used in mice and guinea pigs, the production of antibody against S-1090 was less frequent in comparison with other antibiotics such as cefmetazole (CMZ) and cefotiam (CTM). When hypersensitivity-eliciting antigenicity of S-1090 was examined using S-1090 as an eliciting antigen in ASA and PCA tests, positive ASA and PCA were observed in guinea pigs and positive PCA in a C3H/He mouse. Hypersensitivity-eliciting antigenicity was also observed in other reference antibiotics, i.e. cephalothin (CET), CMZ and CTM. Immunological cross-reactivity among S-1090, penicillin G (PCG), CET, CMZ and CTM was tested by ASA and PCA tests. S-1090 was found to immunologically cross-react only with CET in guinea pigs. In the present study, immunological cross-reactivities were also noted between PCG and CET, PCG and CMZ, PCG and CTM, and between CET and CMZ. In in vitro direct Coombs' test using human red blood cells, S-1090.Na, PCG and CET gave positive reactions at the final concentrations of 40 mg/mL, 20 to 40 mg/mL and 2.5 to 10 mg/mL, respectively.

Enhancing effect of dietary oil emulsions on immune responses to protein antigens fed to mice.

Repeated intragastric administration of beta-lactoglobulin (beta-Lg) with emulsified soybean oil elicited an antigen-specific, systemic humoral immune response in different strains of mice. The antibody response was enhanced as the dose of oil was increased and the particle size of emulsions was decreased. Feeding of aqueous beta-Lg could induce the antibody response only when emulsified oil was fed almost simultaneously. However, the emulsion-driven humoral immune response was not observed when mice were treated with anti-CD40 ligand antibody or in athymic mice. It is likely that the intestinal coexistence of emulsified oil with dietary antigens modulates the immune system to crucially support B cell response. A practical application of the present results to the prevention of cow's milk protein sensitization in infants is proposed.

Increased urinary phosphate excretion in pseudohypoparathyroidism type II with long-term treatment with phosphodiesterase inhibitor.

A 58-year-old woman was diagnosed to have pseudohypoparathyroidism (PHP) type II because of the absence of an increase of urinary phosphate secretion, despite a marked increase in urinary cAMP excretion on the Ellsworth-Howard test. We treated the patient with a cyclic-nucleotide phosphodiesterase inhibitor, theophylline, resulting in increased urinary phosphate and cAMP excretions. Dibutyl cAMP administration induced the increase in the urinary phosphate excretion. In this case, the unresponsiveness of the urinary phosphate secretion to cAMP was recovered by a high dose of cAMP or long-term administration of a phosphodiesterase inhibitor. These data imply that cAMP responsiveness to renal tubular phosphate reabsorption should be more strictly elucidated in the patient with PHP type II.

Therapeutic effect of Oren-gedoku-to extract on stress-induced acute gastric mucosal lesions in rats.

Oral administration of Oren-gedoku-to extract (TJ-15), a traditional Chinese herbal medicine for the therapy of gastric ulcers and gastritis, dose-dependently prevented the progression of acute gastric mucosal lesions in rats with water immersion restraint (WIR) stress. The preventive effect of TJ-15 on the lesion progression was stronger than that of Saiko-keishi-to extract (TJ-10) or Shigyaku-san extract (TJ-35), each of which is a traditional Chinese herbal medicine for the therapy of gastric ulcers and gastritis, when compared on the basis of a single dosage of each medicine for adults. This TJ-15 administration attenuated increases in gastric mucosal lipid peroxide concentration and xanthine oxidase and myeloperoxidase activities with the gastric mucosal lesion progression and recovered the decreased gastric mucosal non-protein SH concentration found at a progressed stage of the gastric mucosal lesions. These results indicate that TJ-15 exerts a therapeutic effect on WIR stress-induced acute gastric lesions in rats more strongly than TJ-10 or TJ-35, and suggest that the therapeutic effect of TJ-15 could be due to its preventive actions on lipid peroxidation and sulphydryl oxidation via oxygen free radicals generated by the xanthine-XO system and infiltrated neutrophils in the gastric mucosa and on neutrophil infiltration into the tissue.

Inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on hepatic triglyceride accumulation with the progression of carbon tetrachloride-induced acute liver injury in rats.

The inhibitory effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on hepatic triglyceride (TG) accumulation with the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). TJ-15 at a dose of 100, 250 or 500 mg/kg body weight (BW) was orally administered to male Wistar rats aged 7 weeks, 6 h after the intraperitoneal injection of CCl4 (1.0 ml/kg BW) at which time apparent liver injury and hepatic TG accumulation occurred. TJ-15 significantly prevented not only the progression of liver injury but also inhibited hepatic TG accumulation with the progression of the injury in a dose-dependent manner when these effects were examined 24 h after CCl4 injection. In CCl4-untreated rats with oral administration of TJ-15 at a dose of 100, 250 or 500 mg/kg BW, liver and serum TG concentrations decreased depending on the dose of the herbal medicine. These results indicate that in rats intoxicated once with CCl4, orally administered TJ-15 can inhibit hepatic TG accumulation with the progression of acute liver injury by its decreasing action on serum and liver TG levels, leading to a prevention of the progression of the liver injury.

Preventive effect of oren-gedoku-to (huanglian-jie-du-tang) extract on progression of carbon tetrachloride-induced acute liver injury in rats.

The effect of oral administration of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). When TJ-15 at a dose of 500 mg/kg body weight (b.w.) was administered to male Wistar rats aged seven weeks 6 hours after i.p. injection of CCl4 (1.0 ml/kg b.w.), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found 24 hours after the injection judging from the activities of serum transaminases and other indices of liver cell damage. An increase in lipid peroxide level and decreases in reduced glutathione level and superoxide dismutase (SOD) activity occurred in the liver at 6 and 24 hours after CCl4 injection. Serum SOD activity increased 24 hours after CCl4 injection. Post-oral TJ-15 administration significantly ameliorated all these changes found at 24 hours after CCl4 injection. An increase in liver triglyceride level and a decrease in serum triglyceride level also occurred 6 and 24 hours after CCl4 injection. Post-oral TJ-15 administration prevented the increase in liver triglyceride level at 24 hours after CCl4 injection. Although the activity of liver tryptophan 2,3-dioxygenase (TDO), a marker of the inhibition of liver protein synthesis by CCl4, decreased 6 and 24 hours after injection of the toxicant, post-oral TJ-15 administration had no effect on this decrease in TDO activity at 24 hours after the injection. These results indicate that oral TJ-15 administration can prevent the progression of acute liver injury in CCl4-injected rats, and suggest that this prevention could be due to the action of TJ-15 to scavenge free radicals formed in the liver and to inhibit triglyceride accumulation in the liver.

Comparative study of oral and parenteral administration of sho-saiko-to (xiao-chaihu-tang) extract on D-galactosamine-induced liver injury in rats.

The preventive effect of Sho-saiko-to (Xiao-Chaihu-Tang) extract (TJ-9) on the progression of D-galactosamine (GaIN)-induced liver injury was examined in five week-old male Wistar rats with oral (p.o.) or intraperitoneal (i.p.) administration of the same dose of TJ-9. Rats treated once with GaIN (500 mg/kg body weight, i.p.) received TJ-9 at a dose of 1.0 g/kg body weight (p.o. or i.p.) 2 hours after GaIN treatment at which time an apparent liver injury occurred. Both p.o. and i.p. administration of TJ-9 showed similar significant prevention against the progression of liver injury 24 hours after GaIN injection. Although total protein and albumin concentrations in serum and protein concentration in the liver decreased with the progression of GaIN-induced liver injury, oral or i.p. administration of TJ-9 prevented these decreases in similar degree. However, decreases in serum and liver triglyceride concentration with the progression of liver injury were not attenuated after p.o. or i.p. administration of TJ-9. The activities of liver 5'-nucleotidase and glucose-6-phosphatase, marker enzymes of liver plasma and microsomal membranes, respectively, decreased during the progression of liver injury. A similar preventive effect on the decrease of both enzyme activities was found after p.o. or i.p. administration of TJ-9. These results indicate that the preventive effect on progression of GaIN-induced liver injury by oral or i.p. administration is approximately equal, and that the effect may be through improving the impaired liver protein synthesis and disrupted liver plasma and microsomal membranes in a similar degree.

[A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in rats].

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 4 weeks was studied in Slc:SD rats at doses of 4, 20 and 100 micrograms/kg/day as low, mid and high dose levels. 1. One male and female at high dose died probably due to stress and circulatory failure. One female at mid dose died with clonic convulsion considered to be results in attached error of a neck collar. Survival of rats showed reddish tear, reddening and desquamation of the skin at application site, and vocalization at all groups including control. Furthermore, abnormal gait, dirty hair, emaciation and opacity of the eyeball surface in both sexes were observed at high dose. 2. A decreased body weight and a slight increased water consumption in both sexes, and a decreased food consumption in males were observed at high dose. 3. An increased incidence of corneal opacity was noted significantly in both sexes as compared with control at high dose. Urinalysis revealed an increased Ca excretion in both sexes at more than mid dose, and lower pH in females at mid dose and in both sexes at high dose, and a decreased urinary volume in males at high dose. The increases of neutrophil and serum beta-globulin ratios in females, and serum Ca level in both sexes were observed at high dose. The increased mineralization of the cornea in males at mid dose and in both sexes at high dose, and of the Kidney in males at high dose were observed. At the skin of application site, cellular infiltration in the epidermis and dermis in both sexes at more than mid dose was observed. Furthermore, hyperplasia of the squamous cell in females, and hyperkeratosis in the epidermis and hypertrophy of the sebaceous gland in both sexes were observed at high dose. 4. After a 4-week recovery period, the changes related with application disappeared except for opacity of the eyeball surface and cornea, and mineralization of organs. 5. On the basis of results obtained in the present study, it is considered that 4 micrograms/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

[A 26-week repeated subcutaneous dose toxicity study of calcipotriol (MC903) followed by a 5-week recovery test in rats].

A 26-week repeated subcutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 5 weeks was studied in Slc:SD rats at doses of 0.4, 2 and 10 micrograms/kg/day as low, mid and high dose levels. 1. No mortality during the experimental period was observed in both sexes of all groups including control. An increased incidence of opacity of the eyeball surface in males was noted at high dose. There were no difference in body weight and food consumption between control. An increased water consumption in both sexes was observed at high dose. 2. An increased incidence of the corneal opacity was noted significantly at high dose in both sexes compared with that observed in control. Urinalysis revealed the increased excretions of Ca at more than mid dose, and Na, Cl and IP in males at high dose, and an decreased urinary volume in females and lower pH in both sexes at high dose. An increased serum Ca level in males at mid dose and in both sexes at high dose, and an elevated ALP activity in males at high dose were observed. The increased weights of the kidney in males at more than mid dose and adrenal gland in both sexes at high dose were observed. The increased incidence of mineralization of the cornea and kidney was noted significantly in males at more than mid dose as compared with control. Dilatation of endoplasmic reticulum of distal tubular cells of the kidney in both sexes was observed at high dose on electron microscopic examination. 3. After a 5-week recovery period, the changes related with the treatment of MC903 almost disappeared except for mineralizations of the cornea and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 administered subcutaneously in both sexes of rats.

[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in rats].

A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in Slc:SD rats at doses of 0.8, 4 and 20 micrograms/kg/day as low, mid and high dose levels. 1. No mortality were observed in both sexes of all groups including control. An increased water consumption was observed in females at mid dose and in both sexes at high dose. 2. An increased incidence of the corneal opacity in males at mid dose and in both sexes at high dose was noted significantly as compared with that observed in control. Urinalysis revealed a slight increased urinary volume, increased excretions of Ca and IP, and lower pH in both sexes at more than mid dose. Levels of the serum IP in females and Ca in both sexes were elevated at high dose. 3. The increased weights of the kidney in males and adrenal gland in females were observed at high dose. The kidney in females at mid dose and in both sexes at high dose showed a higher incidence of mineralization than in control. Furthermore, osteosclerosis of the sternum and femur in both sexes, and hyperkeratosis of the skin at application site in females at high dose were observed. Electron microscopic examination revealed no abnormality in the liver and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.8 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

[An antigenicity study of calcipotriol (MC903)].

Antigenicity of calcipotriol (MC903), an anti-psoriasic agent, was investigated in mice and guinea-pigs. 1. In mice, MC903 administered alone or with an adjuvant (Alum) did not result in the production of MC903-specific IgE antibody. 2. In guinea-pigs sensitized with MC903 alone or plus an adjuvant (FCA), systemic anaphylaxis was not induced by challenging with MC903. IgG1 antibody in MC903-sensitized guinea-pigs was not detected by the 4-hr PCA test. 3. Ovalbumin induced the production of ovalbumin-specific IgE antibody in mice, and ovalbumin-specific IgG1 antibody in guinea-pigs. Intense systemic anaphylaxis in the ovalbumin-sensitized guinea-pigs was induced by challenging with ovalbumin. 4. Results obtained in the present study suggest that MC903 does not induce the production of IgE antibody in mouse, and IgG1 antibody in guinea-pig, and in MC903-sensitized guinea-pig systemic anaphylaxis is not induced by challenging with MC903.

Preventive effect of dai-saiko-to (da-chai-hu-tang) extract on disrupted hepatic active oxygen metabolism in rats with carbon tetrachloride-induced liver injury.

In order to clarify the preventive action of Dai-Saiko-to (Da-Chai-Hu-Tang) extract (TJ-8) on the progression of acute liver injury in rats intoxicated with carbon tetrachloride (CCl4), we examined the effect of post-oral TJ-8 administration on hepatic active oxygen metabolism following the progression of this liver damage. When TJ-8 (1.0 g/kg body weight) was administered orally to male Wistar rats aged five weeks 2 hrs after i.p. injection of CCl4 (1.0 ml/kg body weight), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found at 24 hrs after injection, judging from the activities of serum transaminases, indexes of liver cell damage. Liver cytosolic superoxide dismutase (SOD) activity decreased 2 and 24 hrs after CCl4 injection, while liver cytosolic catalase and glutathione reductase (GSSG-R) activities decreased 24 hrs after the injection. At 2 and 24 hrs after CCl4 treatment, liver cytosolic Se-containing glutathione peroxidase (GSH-px) activity did not change and liver cytosolic glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased. Post-oral TJ-8 administration significantly ameliorated decreases in liver SOD, catalase, and GSSG-R activities at 24 hrs after CCl4 injection, but did not affect liver Se-GSH-px and increased liver G-6-PDH activities at 24 hrs after the injection. Although increased liver lipid peroxide level and decreased liver reduced glutathione and ascorbic acid levels were observed 2 and 24 hrs after CCl4 injection, post-oral TJ-8 administration significantly prevented these changes found at 24 hrs after injection. These results indicate that post-oral TJ-8 administration can prevent the progression of acute liver injury in CCl4-injected rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.

Artificial fiber complexes composed of cellulose and guar gum or psyllium may be better sources of soluble fiber for rats than comparable fiber mixtures.

Three fiber complexes composed of cellulose and the same weight of guar gum, cornstarch or psyllium were constructed as three-dimensional networks of cellulose fiber filled with the soluble components. Physiological properties of these fiber complexes were examined in comparison with a mixture of powdered cellulose and the corresponding polysaccharides at a ratio of 1:1 in rats. Another group of rats was fed a fiber-free diet. Body weight gain in the guar gum-cellulose mixture group, but not in guar gum-cellulose complex group, was lower than that of the fiber-free group. The cecal walls in the groups fed the guar gum-cellulose and psyllium-cellulose mixture diets were heavier than those in the corresponding fiber complex-fed groups. Weights of the small intestinal wall and ileal mucosa were also greater in the guar gum-cellulose mixture-fed group than in the guar gum-cellulose complex-fed and the fiber-free diet-fed groups. Fermentable energy in dietary fiber estimated from fecal energy excretion, short-chain fatty acid contents and in vitro short-chain fatty acid production rates in the cecum of the complex-fed groups were similar to those in the fiber mixture-fed groups. However, butyric acid content and production rate in the group fed the guar gum-cellulose complex were markedly higher than in the other groups. The lowering effects of guar gum-cellulose and psyllium-cellulose mixtures on plasma cholesterol concentration tended to be greater than those of guar gum-cellulose and psyllium-cellulose complexes. These findings demonstrate that the artificial fiber complexes supply soluble fibers without increasing mechanical stress to the intestines and decreasing cecal fermentation.

Roles of central nicotinic receptors in regulation of gastric functions.

In the first part of this paper, the effects of single administration of nicotine on gastric motility of urethane-anesthetized rats are briefly summarized from our recently reported papers. Then, the effects of repeated administration of nicotine on the nicotine-induced changes in gastric motility and release of hypothalamic noradrenaline, in vitro, are described, with special references to up-regulation of nicotinic receptors. Nicotine 0.1 nmol administered into the dorsal motor nucleus of the vagus (DMV) elicited a dual change, a decrease followed by an increase in gastric motility. Intravenous administration of nicotine 300 nmol/kg decreased gastric motility. This decrease in gastric motility was inhibited by microinjection of hexamethonium into the DMV and was terminated by bilateral vagotomy. In animals pretreated with nicotine 200 nmol intracerebroventricularly (icv) administered once a day for 5 days, nicotine 100 nmol administered icv induced the decrease but not the increase in gastric motility. In conclusion, nicotine activates nicotinic receptors in the DMV and a resultant vagally-mediated dual change in gastric motility occurs. Furthermore, gastric inhibitory mechanisms in the DMV are susceptible to nicotine more than the excitatory mechanisms, and desensitization to nicotine occurs easily in the excitatory mechanisms.

[The effects of sairei-tô on nephrotoxic serum nephritis in rats--possible effects on intraglomerular cell mediated immunity].

Sairei-tô, one of the herb drugs, has been demonstrated to have several effects. Clinically, evidence have been accumulated showing that sairei-tô has been able to reduce the frequency of relapse in minimal change nephrotic syndrome. It has also found that sairei-to has improved proteinurial in minimal change nephrotic syndrome as well as chronic glomerulonephritis in man. Although the mechanism of such effects is still unclear, it is supposed that its immune modulating actions that has been reported. In this study, we quantitated the number of intrarenal Ia positive cells and T cells in nephrotoxic nephritis in rats in order to clarify the intrarenal immune actions of sairei-tô on immune mediated glomerulonephritis. Four groups of rats with nephrotoxic nephritis were experimented on. The first group was the controlled group, had no treatment whatsoever. The second group was administered with MPSL (solu-medrol 20 mg/kg, alternate day). The fourth group with both sairei-tô and MPSL. The level of proteinuria in three groups treated was almost the same, that is, less than that of controlled group. On light microscopy, sairei-tô suppressed glomerular inflammation such as endocapillary proliferative lesions and mesangial expansion, which were shown in controlled group. The histological improvement was almost the found in rats treated with MPSL and both. Sairei-tô suppressed infiltrations of intraglomerular Ia positive cells (P less than 0.01) and T cells (P less than 0.01) on the 7th day and 14th day as well. Remarkable suppression of T cells infiltration was noted in rats treated with MPSL along with sairei-to on the 14th day (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Polyol and vacuole formation in cultured canine lens epithelial cells.

Polyol accumulation and myo-inositol depletion were accompanied by extensive vacuole formation in cultured canine lens epithelial cells that were incubated for up to 96 hr in growth medium supplemented with 30 mM D-galactose or 30 mM D-glucose. These changes did not occur in cells incubated in a hypergalactosemic or hyperglycemic medium which also contained an aldose reductase inhibitor (20 microM sorbinil). In addition, these changes were not observed in lens cells incubated in growth medium supplemented with either 30 mM mannitol, which is known to enter cells only slowly, or in 30 mM L-galactose, which is not a substrate for aldose reductase. The vacuoles were visible at the ultrastructural level after 6 hr of incubation in 30 mM D-galactose and increased in both number and size with time. These vacuoles had a unique fine structure. They did not result from swelling of mitochondria or other cell organelles. As demonstrated cytochemically, they did not represent either lysosomes or Golgi saccules. The proliferation pattern of cells incubated with 30 mM D-galactose was clearly different from that of control cells, but approached normal when an aldose reductase inhibitor was added to the incubation medium. Together these findings suggest that vacuole formation and altered cell proliferation were caused by polyol accumulation and/or myo-inositol loss, both of which result from aldose reductase activity.

Crohn disease in systemic lupus erythematosus: a case report.

A 15-year-old girl with systemic lupus erythematosus (SLE) in remission for 3 years showed abdominal pain and bloody stools. No evidence for exacerbation of SLE was obtained. An air-contrast barium enema examination and colonoscopy revealed findings typical of Crohn disease. Despite the rarity of the combination, patients with SLE showing gastrointestinal manifestations might need evaluation for Crohn disease.