[Nutritional prevention of urological tumours]. / Alimentäre Prävention urologischer Tumoren.

Through the last decade considerations on the role of vitamins and antioxidants in the primary prevention of genitourinary tumors have changed dramatically. In spite of all efforts, the efficacy of a specific compound has not been proven so far. In consequence, recommendations to use vitamins or other supplements for the primary prevention of urological tumors should be avoided. However, there is some evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet may not only prevent prostate cancer (PCA) but also harbour additional beneficial effects on general health. Although quantification of these findings may be difficult, it becomes evident that these measures will have additional synergistic effects on cardiovascular diseases. Considering the large number of PCA patients dying not cancer-related but from concomitant diseases, primary prevention in particular of PCA should always also consider the general health of the target population. More recent studies suggest a potential effect of nutritional compounds on biochemical tumour recurrence in PCA patients after definite therapy. These observations may serve as a starting point for validation within controlled clinical trials.

[Phytotherapy of benign prostate syndrome and prostate cancer: better than placebo]. / Phytotherapie bei benignem Prostatasyndrom und Prostatakarzinom : Besser als Placebo?

In some countries plant extracts have belonged to the most popular drugs for the treatment of the benign prostatic syndrome (BPS) for decades; however, only few of the large number of published studies meet the criteria of the WHO benign prostatic hyperplasia (BPH) consensus conference. The few placebo-controlled long-term (study period >6 months) studies suggest a positive effect of some extracts (saw palmetto fruit, ß-sitosterol, urtica, rye grass and a saw palmetto/urtica combination) on lower urinary tract symptoms (LUTS), urinary flow rate, post-void residual volume but effects on prostate volume or prostate-specific antigen (PSA) were only inconsistently demonstrable. To date no study has proven an effect on disease progression, such as acute urinary retention or need for surgical interventions. Due to the controversial data various extraction techniques and compositions of various products, neither American, European, British nor German BPH guidelines recommend plant extracts for the indication BPS although some placebo-controlled trials provided encouraging data. Further prospective studies according to WHO standards are required to determine the role of plant extracts for the management of BPS. For the indication of prostate cancer (PCa) plant extracts have been evaluated for disease prevention and management of several tumor stages but none of these studies have provided convincing evidence that plant extracts are superior to placebo and none of the Pica guidelines have recommended their use.Based on current knowledge plant extracts can never supplement evidence-based PCa management and should be used only in addition to the standard treatment. There is no scientific evidence for the use of dietary supplementation with high doses of vitamins or selenium-containing products.

[Chemoprevention of prostate cancer - a plea]. / Chemoprävention des Prostatakarzinoms - Ein Plädoyer.

The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way.

[Prevention of uro-oncological diseases]. / Prävention uroonkologischer Erkrankungen.

During the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has changed dramatically. Despite all efforts the efficacy of a specific compound has not yet been proven and as a consequence recommendations for the use of vitamins or other supplements for tumor prevention should no longer be given. In contrast life style modification might be helpful as recent investigations suggested that smoking not only promotes the development of bladder cancer but is also involved in prostate and renal cell carcinogenesis. In addition there is some evidence that moderate food consumption, reduction of dairy product consumption and an Asian or Mediterranean diet can prevent prostate cancer and also harbor additional beneficial effects for general health. These observations should be the starting point of future epidemiological research. This may be considered as a change of paradigm in prostate cancer prevention. In contrast there is clear evidence of the efficacy of chemoprevention using 5α-reductase inhibitors as the use of finasteride and dutasteride significantly reduces the detection of prostate cancer. However, translation of these findings into urological practice remains a matter of controversial discussion.

Prevention strategies for prostate cancer.

Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion.

[Secondary and tertiary prevention of urological tumors]. / Sekundär- und Tertiärprävention urologischer Tumore.

The amount and quality of available data on secondary and tertiary prevention of urological tumors are to a large extent unsatisfactory. In the areas of nutrition and supplementary diet the consumption of tomatoes and especially tomato products could have a beneficial effect on the course of the disease for patients with prostate cancer, whereas there is evidence that the consumption of foodstuffs containing calcium (milk and milk products) and linolenic acid as well as a fat-rich diet accelerate tumor progression. Despite as yet unsatisfactory data, men with urothelial tumors or prostate cancer should abstain from smoking and undertake sports activities. For medicinal measures the administration of 5-alpha-reductase inhibitors and bone-promoting substances for patients with prostate cancer are under discussion. The effectiveness of the substances zoledronate and denosumab has been demonstrated in prospective randomized studies. The authors recommend that the scientifically neglected field of tertiary prevention of urological tumors should in future be included as a core factor of scientific investigations.

Automated multiple development thin layer chromatography for calystegines and their biosynthetic precursors.

Automated multiple development thin layer chromatography (AMD-TLC) was used for separation of calystegines, a class of nortropane alkaloids, and of precursors of their biosynthesis. The calystegines differ in the number of hydroxyl groups at the nortropane ring system and in the substitution pattern. A combination of TLC methods allows the separation of the individual calystegines and separation of possible precursors of the biosynthesis. Solvent combination, development time, the number of development steps, the drying time between each run and the preconditioning parameters of the silica gel TLC plates were optimised. Limits of detection were evaluated for several detection reagents.

Pulsed amperometric detection of calystegines separated by capillary electrophoresis.

Calystegines are polyhydroxyalkaloids with a nortropane skeleton. They are oxidized by pulsed amperometry at a gold electrode due to their vicinal hydroxyl groups similar to monosaccharides, but at a slightly higher potential. Compared to carbohydrates, calystegines exhibit lower acidity, thus the effective electrophoretic mobility as anions in 0.1 M NaOH is lower, independent of their molecular mass. The acidity and mobility of calystegines increase with the number of hydroxyl groups. The influence of temperature and power dissipation in the capillary and changes of the inner surface on the migration times was eliminated by cooling and subtraction of the electroosmotic flow velocity. The high resolving power of capillary zone electrophoresis allows the separation of calystegines with the same number of hydroxyl groups. Detection is linear from 2 to 200 mg L(-1) with a 1 nL injection volume. Calystegines were determined in crude plant sap after filtration without further sample purification.

Nutrition and prostate cancer.

Nutrition is apparently a major risk factor for the development and progression of prostate cancer. Based on experimental studies and epidemiologic data mainly from case-control studies or cohort studies, there is strong evidence that reduction of the total energy consumption, a diet comprising less than 30% fat, and increased intake of phytoestrogens, vitamins D and E and selenium could yield a decreased prostate cancer incidence. Furthermore, some of these measures appear to have antitumoral capacity even in the presence of the disease. These observations have provided a rationale to forward large prospective trials on dietary interventions to prove the efficacy of the concept and further delineate the correlation between nutritional compounds and prostate cancer risk. These chemoprevention trials are either aiming a reduction prostate cancer incidence or a decrease in tumor progression. Depending on the study design, large numbers of individuals need to be enrolled and long follow-up intervals are required thus making such trials highly complex and cost-intensive. However, regarding the potential relevance of chemoprevention on public health, further efforts to identify nutritional factors affecting prostate cancer growth are warranted.

Specificities of the enzymes of N-alkyltropane biosynthesis in Brugmansia and Datura.

The enzymes N-methylputrescine oxidase (MPO), the tropine-forming tropinone reductase (TRI), the pseudotropine-forming tropinone reductase (TRII), the tropine:acyl-CoA transferase (TAT) and the pseudotropine:acyl-CoA transferase (PAT) extracted from transformed root cultures of Datura stramonium and a Brugmansia candida x aurea hybrid were tested for their ability to accept a range of alternative substrates. MPO activity was tested with N-alkylputrescines and N-alkylcadaverines as substrates. TRI and TRII reduction was tested against a series of N-alkylnortropinones, N-alkylnorpelletierines and structurally related ketones as substrates. TAT and PAT esterification tests used a series of N-substituted tropines, pseudotropines, pelletierinols and pseudopelletierinols as substrates to assess the formation of their respective acetyl and tigloyl esters. The results generally show that these enzymes will accept alien substrates to varying degrees. Such studies may shed some light on the overall topology of the active sites of the enzymes concerned.

Distribution of calystegines in several solanaceae.

Calystegines are nortropane alkaloids with glycosidase inhibitor activity. They were found in different plant organs vary remarkably.

The reduction of tropinone in Datura stramonium root cultures by two specific reductases.

In tropane-alkaloid producing plants and root cultures, the reduction of tropinone is a branch-point in secondary metabolism. Two different reductases stereospecifically form the isomeric alcohols tropine (tropan-3 alpha-ol) and pseudotropine (tropan-3 beta-ol). We describe here the purification and characterization of both reductases from transformed root cultures of Datura stramonium. The tropine-forming reductase (TR I, EC 1.1.1.206) was purified 108-fold, the pseudotropine-forming enzyme (TR II, EC 1.1.1.236) was purified 3410-fold to homogeneity. The native molecular weights, both determined by gel chromatography, were 50,700 (TR I) and 77,700 (TR II). In SDS gel electrophoresis a subunit with an M(r) of 27,700 could be identified for TR II. Isoelectric points are at 5.2 (TR I) and 5.7 (TR II). Km values for the physiological substrate tropinone are 1.30 mM (TR I) and 0.11 mM (TR II). NADPH as a cosubstrate shows Km values of 58 microM (TR I) and 16 microM (TR II). NADH is not accepted by either enzyme. The reverse reaction (i.e. oxidation of the alcohol to tropinone) was found only for TR I with a Km of 180 microM. From a detailed analysis of the catalytic activities of TR I and TR II with a range of substrate analogues some key features of the mechanism of reaction can be proposed. The catalytic properties of TR I and TR II are compared with each other and with TR I and TR II activities from other solanaceous species from which these enzymes have been described.