Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea.

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) (n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes.

Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight.

UNLABELLED: We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight. INTRODUCTION: This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight. METHODS: We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism. RESULTS: In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium. CONCLUSIONS: The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.

Effects of citrate on renal stone formation and osteopontin expression in a rat urolithiasis model.

Previous studies have described the inhibitory effects of citrate on calcium oxalate crystallization in place of crystal growth, but the effects of citrate on matrix proteins of stones has not been studied in vivo. To examine the effect of citrate on the matrix, we investigated the effect of citrate on osteopontin (OPN) expression, which we had previously identified as an important stone matrix protein. Control rats were treated with saline while rats of the stone group were treated with ethylene glycol (EG) and vitamin D3, and the citrate groups (low-dose and high-dose groups) were treated with a citrate reagent compound of sodium citrate and potassium citrate, in addition to EG and vitamin D3. The rate of renal stone formation was lower in the citrate groups than in the stone group. This was associated with a low expression of OPN mRNA in citrate-treated rats relative to that in the stone group. Citrate was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that citrate prevents renal stone formation by acting against not only the crystal aggregation and growth of calcium oxalate but also OPN expression.

Effects of allopurinol on renal stone formation and osteopontin expression in a rat urolithiasis model.

BACKGROUND: The inhibitory effect of allopurinol on calcium oxalate urolithiasis has been reported, but its effect on stone matrix proteins has not been studied in vivo. To clarify the effect of allopurinol on the matrix, we investigated its effect on the expression of osteopontin (OPN), which we previously identified as an important stone matrix protein. METHODS: Control rats were not treated. Rats of the stone group were given ethylene glycol (EG) and vitamin D(3), while the allopurinol groups (low-dose group and high-dose group) were treated with allopurinol in addition to receiving EG and vitamin D(3). RESULTS: The rate of renal stone formation was lower in the allopurinol groups than in the stone group. This was associated with a low expression of OPN mRNA in allopurinol-treated rats relative to that in the stone group. CONCLUSION: Allopurinol was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that allopurinol prevents renal stone formation by acting against not only the control of oxalate but also OPN expression.

Inhibitory effects of female sex hormones on urinary stone formation in rats.

BACKGROUND: The effects of female sex hormones on urinary stone formation are not known. This study was conducted to investigate the effects of these hormones on stone formation by using an ethylene glycol (EG) and vitamin D-induced rat urolithiasis model. METHODS: Adult female Wistar rats were fed the same diet for four weeks and were then divided into four groups (N = 10 each). One group was administered 0.5 ml of olive oil three times per week for four weeks as a control. The other three groups were administered 0. 5 microg of vitamin D3 and 0.5 ml of 5% EG three times per week for four weeks. The rats in two of these three groups were oophorectomized, and the rats of the remaining group underwent a sham operation on the day before the start of the four-week treatment period. One of the two oophorectomized groups was then administered a supplementation of female sex hormones (0.1 mg of estrogen and 2.5 mg of progesterone 3 times per week for 4 weeks). On the first day of the fifth week of the experimental period, the degree of crystal deposition was determined histologically, and the calcium content in renal tissue was measured. We also investigated the level of osteopontin (OPN) mRNA in renal tissues by Northern blot analysis. OPN is a matrix protein thought to be a promoter of stone formation. RESULTS: The urinary oxalate excretion, crystal deposition and calcium content in renal tissue and the expression of OPN-mRNA were greater in the oophorectomized rats compared with the controls, and the same parameters were inhibited by the female sex hormone supplementation. CONCLUSIONS: These results suggest that female sex hormones can inhibit renal crystal deposition in EG-treated rats by suppressing the urinary oxalate excretion and the expression of OPN.

The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model.

Kampo medicine is a traditional Japanese therapeutic system which originated in China and was used to treat various diseases for hundreds of years. Kampo medicine had been also used for the cure and the prevention of urinary calculi for many years, but the effect and the mechanism of this use of kampo medicine are unclear. We examined the inhibitory effect of the kampo medicine takusha on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) and vitamin D3 in rats. We also investigated the effect of takusha on osteopontin (OPN) expression, which we previously identified as an important stone matrix protein. The control group rats were non-treated; the stone group rats were administered EG and vitamin D3, and the takusha group was administered takusha in addition to EG and vitamin D3. The rate of renal stone formation was lower in the takusha group than in the stone group; thus, the OPN expression in the takusha group was smaller than in the stone group. Takusha was effective in preventing oxalate calculi formation and OPN expression in rats. These findings suggest that takusha prevents stone formation including not only calcium oxalate aggregation but also proliferation.

[Clinical efficacy of sairei-to in prevention of recurrence of urethral stenosis: report of two cases].

Sairei-to has been reported to inhibit granulation and fibroblast proliferation. We administered Sairei-to (9.0 g/day) to two 77-year-old men with repeated urethral stenosis after transurethral resection of prostate (TUR-P) and examined its clinical effects. Urethral stricture did not recur in these patients for 7 to 8 months. There were no side effects in these patients. Sairei-to is suggested to be useful to prevent recurrence of urethral stricture after a transurethral procedure.

[Effect of Chorei-to on spontaneous discharge of urinary stones after extracorporeal shock wave lithotripsy (ESWL)].

To enhance stone elimination following extracorporeal shock wave lithotripsy (ESWL), we administered Tsumura Chorei-to to 74 patients who underwent the procedure at Kinki University School of Medicine and Kanbara Hospital between July 1990 and March 1991. We established a control group of 75 patients without medication. There was no significant difference between the two groups in terms of gender, age, stone size (mostly less than 20 mm), and stone position. The mean number of days required for complete stone elimination was 16.0 days in the Chorei-to administration group being significantly shorter than the 21.5 days in the control group (p < 0.001). These findings suggested that Chorei-to effectively enhanced the spontaneous discharge of fragmented stones following ESWL.

Immunohistochemical evaluation of p53 and retinoblastoma proteins in relation to hyperthermia treatment: results in human urothelial carcinomas.

Immunohistochemical staining of urothelial tumours using paraffin-embedded tissue blocks was performed for p53 and Retinoblastoma (RB) proteins, to characterize any correlation with sensitivity to hyperthermia treatment. Seventeen patients with primary urothelial tumours (16 of the bladder and one of the ureter) treated at our institute between July, 1987 and March, 1993 were included in this study; tissues investigated consisted of 16 transitional cell carcinomas (TCC) (6 Grade2 (G2), 6 G3, 2 G2 > G3, 1 G3 > squamous cell carcinoma (SCC), 1 undifferentiated carcinoma > G3), and 1 SCC. One case was Tis, 4, 3, 1, and 4, were T1 to T4, respectively, and 4 were post-cystectomy. Clinically, in terms of response to treatment, there were four complete response (CR) cases, four partial response (PR) cases, six no change (NC) cases, and three progressive disease (PD) cases, the total in which treatment was effective thus accounting for approximately half of those examined (CR + PR, 47%). Immunohistochemically, six of eight pre-hyperthermia lesions which demonstrated positive staining for RB were CRs or PRs, 75% of which were high-grade lesions, and 50% exhibited invasion and lymph node metastasis. Only three in total were positive for p53 staining, two of which were T4 and these both responded to treatment. The results suggested that RB gene expression may be related to heat sensitivity to some degree.