A glucosinolate-rich extract of Japanese Daikon perturbs carcinogen-metabolizing enzyme systems in rat, being a potent inducer of hepatic glutathione S-transferase

Purpose

Glucosinolates/isothiocyanates are an established class of naturally occurring chemopreventive agents, a principal mechanism of action being to limit the generation of genotoxic metabolites of chemical carcinogens, as a result of modulation of cytochrome P450 and phase II detoxification enzymes. The objective of this study was to assess whether a glucosinolate-rich extract from Daikon sprouts, containing glucroraphasatin and glucoraphenin, is a potential chemopreventive agent by modulating such enzymes in the liver and lung of rats.

Methods

Rats were exposed to the glucosinolate-rich Daikon extract through the diet, at three dose levels, for 14 days, so that the low dose simulates dietary intake.

Results

At the low dose only, a modest increase was noted in the hepatic dealkylations of methoxy-, ethoxy-, pentoxyresorufin and benzyloxyquinoline that was accompanied by elevated expression of CYP1 and CYP3A2 apoprotein levels. In lung, only a modest increase in the dealkylation of pentoxyresorufin was observed. At higher doses, in both tissues, these increases were abolished. At the same low dietary dose, the Daikon extract elevated markedly glutathione S-transferase activity paralleled by rises in GSTα, GSTμ and GSTπ protein expression. An increase was also noted in quinone reductase activity and expression. Finally, glucuronosyl transferase and epoxide hydrolase activities and expression were also up-regulated, but necessitated higher doses.

Conclusion

Considering the ability of Daikon glucosinolates to effectively enhance detoxification enzymes, in particular glutathione S-transferase, it may be inferred that consumption of this vegetable may possess significant chemopreventive activity and warrants further evaluation through epidemiology and studies in animal models of cancer.     

Current status of surrogacy in Japan and uterine transplantation research

Recent advances in assisted reproductive technology (ART) have made it possible to circumvent many causes of male and female infertility. The right to have a child by ART has been respected for infertile couples. However, there are currently no legal regulations concerning ART in Japan, and this has resulted in social and ethical problems. Surrogacy involves particularly complex medical, ethical, social, and legal issues, and is frequently focused on as a major social concern. Uterine transplantation (UTx) is a potential alternative for young women with uterine factor infertility due to hysterectomy for treatment of a malignant uterine tumor or massive blood loss after delivery, or because of a congenital disease such as Mayer–Rokitansky–Küster syndrome. UTx has been examined in experimental animals as a basis for establishment of fecundity for young women with uterine factor infertility. In this review, we focus on surrogacy in Japan and UTx research, and discuss the current status and concerns in this field.     

An optimization algorithm of dose distribution using attraction-repulsion model (application to low-dose-rate interstitial brachytherapy)

PURPOSE: To optimize dose distribution for prostate cancer in low-dose-rate interstitial brachytherapy, we have developed a new algorithm named the Attraction-Repulsion Model. The purpose was to find the optimal source configuration. METHODS AND MATERIALS: The Attraction-Repulsion Model is used to optimize the dose distribution by finding the best seed configuration. We arranged grids at intervals of a certain space inside and established target and critical organs as areas of interest. We can make an attribute for grids, and the grids show attraction or repulsion depending on dose delivered from source. Source position is changed by the forces that the grids impose to the sources. A calculation was done repeatedly until the attraction and repulsion forces reached a balance. The optimal configuration was established when the sources reached a stable distribution in time. To evaluate the optimization plan, dose-volume histograms were used. RESULTS: Source configuration can be optimized automatically. The calculation time was approximately 5 min. The V100, V150, V200, and D90 of the target were 95%, 39%, 9%, and 157 Gy, respectively. V150 of the urethra and V80 of the rectum were 2% and 0%, respectively. CONCLUSION: This method can optimize the dose distribution objectively.     

A case of coring on using a 1% Diprivan vial]

We report a case in which two fragments due to coring from the rubbercap of a 50 ml Diprivan vial were detected only immediately before infusion to a patient. The attending anesthesiologist noticed the foreign bodies by chance. The rubbercap was punctured only once, but the two foreign bodies from the syringe were proved to be from the rubbercap by infrared spectrometer analysis. It is difficult to recognize the small fragments in Diprivan which is white unclear emulsion. Therefore, anesthesiologists should be aware of the danger of coring.     

Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor

Background and aimsContinuous glucose monitoring improves glycemic control in diabetes. This study compared the accuracy of the Dexcom G5 Mobile (Dexcom, San Diego, CA) transcutaneous sensor (DG5) and the first version of Eversense (Senseonics,Inc., Germantown, MD) implantable sensor (EVS).Methods and resultsSubjects with type 1 diabetes (T1D) and using EVS wore simultaneously DG5 for seven days. At day 3, patients were admitted to a clinical research center (CRC) to receive breakfast with delayed and increased insulin bolus to induce glucose excursions. At CRC, venous glucose was monitored every 15 min (or 5 min during hypoglycemia) for 6 h by YSI 2300 STAT PLUS? glucose and lactate analyzer. At home patients were requested to perform 4 fingerstick glucose measurements per day.Eleven patients (9 males, age 47.4 ± 11.3 years, M±SD) were enrolled. During home-stay the median [25th-75th percentile] absolute relative difference (ARD) over all CGM-fingerstick matched-pairs was 11.64% [5.38–20.65]% for the DG5 and 10.75% [5.15–19.74]% for the EVS (p-value = 0.58). At CRC, considering all the CGM-YSI matched-pairs, the DG5 showed overall smaller median ARD than EVS, 7.91% [4.14–14.30]% vs 11.4% [5.04–18.54]% (p-value<0.001). Considering accuracy during blood glucose swings, DG5 performed better than EVS when glucose rate-of-change was ?0.5 to ?1.5 mg/dL/min, with median ARD of 7.34% [3.71–12.76]% vs 13.59% [4.53–20.78]% (p-value<0.001), and for rate-of-change < -1.5 mg/dl/min, with median ARD of 5.23% [2.09–15.29]% vs 12.73% [4.14–20.82]% (p-value = 0.02).ConclusionsDG5 was more accurate than EVS at CRC, especially when glucose decreased. No differences were found at home.     

Dose–volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours

BACKGROUND AND PURPOSE: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. MATERIALS AND METHODS: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. RESULTS: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP=5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. CONCLUSIONS: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT.     

Bartter's syndrome with gouty arthritis.

A 45-year-old woman with Bartter's syndrome complicated with gouty arthritis is reported. Bartter's syndrome was diagnosed from hypokalemia, metabolic alkalosis, high plasma renin activity, normal blood pressure and attenuated pressor response to exogenous angiotensin II infusion. Serum uric acid was 11.8 mg/dl, the renal clearance of uric acid was low (3.0 ml/min) and fractional excretion of uric acid (FEUA) was 7.0%, being the lower limit of the normal range. Fractional excretion of phosphate was low (5.3%) and fractional free water clearance per fractional distal sodium delivery was 0.51. The mechanism of hyperuricemia in this case is discussed.