Pentacyclic triterpenes from Terminalia arjuna show multiple benefits on aged and dry skin.

BACKGROUND: Pentacyclic triterpenoids improve epidermal barrier function and induce collagen production. Here, their effects on cutaneous aging by means of objective instrumental measurements were elucidated. METHODS: Reconstituted human epidermis, cultivated keratinocytes and fibroblasts were incubated with Terminalia arjuna triterpenes (T. arjuna bark extract), and mRNA and protein expression of various genes was determined using microarray analysis, qRT-PCR and ELISA techniques. Clinical efficacy of T. arjuna bark extract versus vehicle control cream was elucidated in 30 patients and transepidermal water loss (TEWL), skin hydration and elasticity were measured. Another 30 female patients in their postmenopausal phase were treated with a similar regime, and skin sebum content, cutaneous blood microcirculation and skin density/echogenicity were assessed. RESULTS: Incubation with T. arjuna triterpenes increased FGF-2, TSP-1, TGF-ß and CTGF expression, and VEGF secretion in vitro. Elevated lactate dehydrogenase release upon sodium dodecyl sulphate challenge was reversed by the application of T. arjuna bark extract. T. arjuna bark extract decreased TEWL, improved skin moisturization, reduced scaliness and led to significantly improved skin elasticity. Also, increases in blood microflow and skin sebum content as well as improved skin thickness/echogenicity were noted on postmenopausal skin, resulting in visible reduction of sagging skin on the jowls as demonstrated by digital photography. CONCLUSION: T. arjuna bark extract appears as an innovative active ingredient that exerts versatile antiaging properties in vitro and in vivo.

A fast algorithm to find optimal controls of multiantenna applicators in regional hyperthermia.

The goal of regional hyperthermia is to heat up deeply located tumours to temperatures above 42 C while keeping the temperatures in normal tissues below tissue-dependent critical values. The aim of this paper is to describe and analyse functions which can be used for computing hyperthermia treatment plans in line with these criteria. All the functionals considered here can be optimized by efficient numerical methods. We started with the working hypothesis that maximizing the quotient of integral absorbed power inside the tumour and a weighted energy norm outside the tumour leads to clinically useful power distributions which also yield favourable temperature distributions. The presented methods have been implemented and tested with real patient data from the Charité Berlin. Campus Virchow-Klinikum. The results obtained by these fast routines are comparable with those obtained by relatively expensive global optimization techniques. Thus the described methods are very promising for online optimization in a hybrid system for regional hyperthermia where a fast response to MR-based information is important.

Differential selection of multidrug efflux mutants by trovafloxacin and ciprofloxacin in an experimental model of Pseudomonas aeruginosa acute pneumonia in rats.

The ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo was studied in a model of acute Pseudomonas aeruginosa pneumonia in rats. Twelve hours after intratracheal inoculation of 10(6) CFU of P. aeruginosa strain PAO1 enmeshed in agar beads, two groups of 12 rats were treated by three intraperitoneal injections of each antibiotic given every 5 h. Dosing regimens were chosen to obtain a comparable area under the concentration-time curve from 0 to infinity/MIC ratio of 27.9 min for trovafloxacin (75 mg/kg of body weight) and of 32.6 min for ciprofloxacin (12.5 mg/kg). Twelve rats were left untreated and served as controls. Rats were sacrificed 12 h after the last injection (34 h after infection) for lung bacteriological studies. Selection of resistant bacteria was determined by plating lung homogenates on Trypticase soy agar plates containing antibiotic. In untreated animals, the frequency of resistant colonies was 10-fold higher than in agar beads. Compared to controls, both treatment regimens resulted in a 2-log reduction of lung bacterial load. The frequency of resistant colonies was 10-fold less with trovafloxacin than with ciprofloxacin at twice the MIC (7.4 x 10(-5) versus 8.4 x 10(-4), respectively) (P < 0.05) and at four times the MIC (6.2 x 10(-4) versus 5.0 x 10(-5), respectively) (P < 0.05). A multidrug resistance phenotype typical of efflux mutants was observed in all 41 randomly tested colonies obtained from treated and untreated rats. In agreement with in vitro results, trovafloxacin and ciprofloxacin preferentially selected MexCD-OprJ and MexEF-OprN overproducers, respectively. These results demonstrate the differential ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo and highlight the rapid emergence of those mutants, even without treatment.

Genotyping of human apolipoprotein E alleles by the new qualitative, microplate-based CASSI-detection assay.

A new qualitative PCR product detection assay called competitive amplified single mutation detection by selective probe hybridization immunoassay (CASSI) was developed for genotyping the most common apolipoprotein E (apoE) polymorphisms. Single target DNA strands immobilized using biotin on streptavidin-coated microplates were hybridized in separate wells with two distinct, 5'-fluorescein isothiocyanate (FITC)-labeled oligonucleotides, complementary to either the 112Arg or 158Arg encoding site. With this assay, only correctly matched hybrids that form between probe and target DNA can be cleaved with the HhaI restriction endonuclease, leading to loss of probe label in corresponding wells. However, allele-specific, probe-target mismatches due to G-->T exchanges in the HhaI recognition sequences are not cleaved. After digestion, the remaining microplate-adsorbed signal is measured colorimetrically by using anti-FITC, Fab-horseradish peroxidase conjugates. Our results show maximum intensity was detected when the respective probe hybridized incompletely to the target (i.e., no cleavage), and minimum signal was obtained when the probe matched the target completely (complete cleavage); whereas, an intermediate signal was recorded at 50% complementarity (i.e., heterozygote alleles). With this assay, we could demonstrate a high prevalence of the apoE2 allele in patients suffering from coronary artery disease even though they displayed normal triglyceride and cholesterol levels. Corresponding results were obtained by CASSI compared with conventional restriction fragment-length polymorphism analysis.