Green tea reduces body fat via upregulation of neprilysin.

BACKGROUND/OBJECTIVE: Consumption of green tea has become increasingly popular, particularly because of claimed reduction in body weight. We recently reported that animals with pharmacological inhibition (by candoxatril) or genetic absence of the endopeptidase neprilysin (NEP) develop an obese phenotype. We now investigated the effect of green tea extract (in drinking water) on body weight and body composition and the mediating role of NEP. SUBJECTS/METHODS: To elucidate the role of NEP in mediating the beneficial effects of green tea extract, 'Berlin fat mice' or NEP-deficient mice and their age- and gender-matched wild-type controls received the extract in two different doses (300 or 600 mg kg-1 body weight per day) in the drinking water. RESULTS: In 'Berlin fat mice', 51 days of green tea treatment did not only prevent fat accumulation (control: day 0: 30.5% fat, day 51: 33.1%; NS) but also reduced significant body fat (green tea: day 0: 27.8%, day 51: 20.9%, P<0.01) and body weight below the initial levels. Green tea reduced food intake. This was paralleled by a selective increase in peripheral (in kidney 17%, in intestine 92%), but not central NEP expression and activity, leading to downregulation of orexigens (like galanin and neuropeptide Y (NPY)) known to be physiological substrates of NEP. Consequently, in NEP-knockout mice, green tea extract failed to reduce body fat/weight. CONCLUSIONS: Our data generate experimental proof for the assumed effects of green tea on body weight and the key role for NEP in such process, and thus open a new avenue for the treatment of obesity.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris.

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.

Selective photothermolysis of hair follicles by normal-mode ruby laser treatment.

This study was designed to evaluate the effect of selective photothermolysis on dark pigmented hair follicles treated with a normal-mode ruby laser (694-nm wavelength, pulse duration 0.5 ms, fluence 20 J/cm2, spot size 2 mm). In 15 volunteers, four test areas each were selected. After shaving, the first area was irradiated once, the second twice, the third three times and the fourth served as control area. A punch biopsy was taken from each volunteer immediately after the first laser treatment. Four weeks after the last irradiation, no effect was found in six cases and little effect in another six cases (50-90% regrowth). Hair regrowth of less than 30% was observed in only three cases. Eight weeks after the last session, no effect was found in 11 cases, little effect in 2 cases (10%) and less than 30% regrowth in only 2 cases. Twelve weeks after the last treatment, no difference could be detected between the areas untreated and treated by laser. The laser parameters applied in this study do not result in effective epilation of body hair. In some cases, a delay in growth of several weeks was noticed.

8-Methoxypsoralen serum levels in poor responders to photochemotherapy. Importance of drug formulation and individual factors.

8-Methoxypsoralen (8-MOP) serum levels of psoriatic patients poorly responsive to photochemotherapy (PUVA) treatment (problem cases) were determined by the HPLC method with 11 single blood probes over 8 hours. Abnormally low or deviated serum levels were found in 7 of 11 PUVA problem patients. There was a great interindividually different first-pass effect for 8-MOP in dependence on the galenic formulation of the 8-MOP brand; therefore, the change to another 8-MOP brand with a modern galenic formulation led only to a slight increase of serum levels, and consequently an increase in the 8-MOP dosage was necessary. It is important to be cautious at this point because patients may show an unproportional increase of 8-MOP serum levels due to the individually limited capacity of biotransformation. The studies of the authors reaffirm the necessity of the determination of 8-MOP serum levels in problem cases of PUVA therapy.

[Pharmacokinetic comparison of 3 8-methoxypsoralen preparations and clinical aspects]. / Pharmakokinetischer Vergleich von drei 8-Methoxypsoralen-Präparaten und klinische Aspekte.

In order to register the inter- and intraindividual variability of serum levels of 8-methoxypsoralen (MOP) (Oxsoralen, n = 12; Geroxalen, n = 46; Mopsoralen, n = 30), we investigated a total of 1,276 serum samples obtained at 11 patient appointments over 8 h in 88 patients and compared the individual serum concentrations - time curves with the pharmacokinetic parameters Cmax (maximal serum concentration) on the time tmax, as well as the AUC value (area under the curve) as a parameter of bioavailability. The individual serum concentration value showed a high interindividual variability (Oxsoralen Cmax: 47-473 ng.ml-1; Geroxalen Cmax: 37-416 ng.ml-1 and Mopsoralen Cmax: 44-300 ng.ml-1) and preparation specific differences (Oxsoralen Cmax: 188 +/- 125 ng.ml-1; tmax: 2.0 +/- 0.6 h; AUC: 461 +/- 322 ng.ml-1.h; Geroxalen Cmax: 193 +/- 87 ng.ml-1; tmax: 0.9 +/- 0.4 h; AUC: 290 +/- 198 ng.ml-1.h; Mopsoralen Cmax: 164 +/- 71 ng.ml-1; tmax: 1.7 +/- 0.5 h; AUC: 389 +/- 221 ng.ml-1.h). On repeated administration of Geroxalen (n = 16) and Mopsoralen (n = 12), minimal intraindividual distributions were noted, so the mean serum concentration curves did not show a significant difference. The importance of 8-MOP serum level determinations for better puva therapy, particularly in therapeutic failure in problem cases, is discussed.

[8-methoxypsoralen serum content of problem patients in PUVA therapy]. / 8-Methoxypsoralen-Serumgehalt bei Problempatienten der PUVA-Therapie.

Beside the stage, expression and course of psoriasis as well as the compliance of patients low or abnormal 8-MOP levels are the cause of the ineffectiveness of the PUVA-therapy, as we could demonstrate in 7 of 11 problem cases. Thus, we determined only a maximal 8-MOP concentration of 47 ng/ml serum as an extreme value in one patient and on other patient had his maximal serum peak 3-4 hours after 8-MOP-application and only a value of 8-MOP of 18 ng/ml serum at the recommended time of irradiation. In this connection a first pass mechanism for 8-MOP by a limited biotransformation capacity in the liver is significant and one basic reason for the interindividual variation. Therefore in these cases the knowledge of the individual serum profiles of 8-MOP is helpful to adapt the time of irradiation to the individual necessities and/or to increase the 8-MOP doses.

Impairment to viability of neutrophils and lymphocytes by angular psoralens and UV-radiation.

The angular psoralen derivative, 4,5'-dimethylangelicin (Dm Agn), both without and with UV-radiation induces under adequate conditions a higher percentage of lethally damaged cultured human polymorphonuclear neutrophils (PMN) as compared with angelicin (Agn). In general, PMN photosensitized with Dm Agn are less resistant than similarly photosensitized lymphocytes. These results suggest that Dm Agn might be used to improve the photochemo (PUVA-)therapy of skin diseases where PMN are of pathogenic importance.