Antiseptic efficacy of two mouth rinses in the oral cavity to identify a suitable rinsing solution in radiation- or chemotherapy induced mucositis.

OBJECTIVES: Oral mucositis caused by intensive cancer chemotherapy or radiotherapy frequently results in pronounced damage of the oral mucosa leading to painful oral hygiene. To support oral care, antimicrobial effective mouth rinses may be used. Thus, the efficacy of a hypochlorite-based mouth rinse (Granudacyn®), assumed to be highly biocompatible because of the compounds being part of the natural pathogen defense, as possible antiseptic agent in case of oral mucositis was compared to that of an octenidine based antiseptic mouth rinse (Octenidol® md). MATERIALS AND METHODS: The study was conducted as monocentric, controlled, randomized, blind cross over comparative study on 20 volunteers. As a proof of principle, we performed the study on orally healthy subjects and not cancer patients. The efficacy was determined as reduction of colony forming units (cfu) on buccal mucosa as well as in saliva. After mouth rinsing for 30 s, samples were taken after 1 min, 15 min, 30 and 60 min. The lg-reduction was calculated as difference between lg-values of cfu pre- and post-treatment. RESULTS: Both antiseptic mouth rinses induced a significant reduction of cfu on buccal mucosa and in saliva 1 min after mouth rinsing. The effect persisted up to 60 min. The octenidine based rinse was significantly superior to the hypochlorite-based rinse up to the last sample 60 min after rinsing. However, the known cytotoxicity of octenidine argues against its application. CONCLUSION: Within the limits of this study, due to its antiseptic efficacy, the hypochlorite-based rinse Granudacyn® can be regarded appropriate to support the oral hygiene in patients with a sensitive oral mucosa during an aggressive cancer chemotherapy and radiation treatment in case of oral mucositis.

Increased responsivity of suspended graphene photodetectors.

The responsivity of graphene photodetectors depends critically on the elevated temperature of the electronic subsystem upon photoexcitation. We investigate the role of the substrate in providing cooling pathways for photoexcited carriers under ambient conditions by partially suspending few-layer graphene over a trench. Through photocurrent microscopy, we observe p-n junctions near the supported/suspended interfaces that produce photothermoelectric currents. Most importantly, we find the photocurrent in suspended p-n junctions to be an order of magnitude larger than in supported structures. This enhancement is attributed to the elimination of a dominant electronic cooling channel via the surface phonons of the polar substrate. Our work documents this mechanism of energy exchange between graphene and its environment, and it points to the importance of dielectric engineering for future improved graphene photodetectors.

Synthesis and biological activity of splitomicin analogs targeted at human NAD(+)-dependent histone deacetylases (sirtuins).

Small molecules interfering with posttranslational modification of histones are of interest as tools to study epigenetic regulation of gene transcription. Specifically, drugs that interfere with histone deacetylation could be useful to induce differentiation, growth arrest as well as apoptotic cell death in tumor cells. One class of histone deacetylases is known as sirtuins some of which (Saccharomyces cerevisiae Sir2) are for example inhibited by the lactone splitomicin leading to telomeric silencing in yeast. However, splitomicin is only a micromolar inhibitor of yeast Sir2 and does not inhibit human subtypes and the lactone is prone to hydrolytic ring opening. In preliminary SAR-studies, splitomicin analogs lacking this hydrolytically labile ring were described as inactive while the naphthalene moiety could successfully be replaced by smaller aromatic rings in a fragment-like dihydrocoumarin. Here we report the synthesis and biological activity of a series of hydrolytically stable analogs with activity against human SIRT1 and 2. These comparatively small compounds characterized by high ligand efficiency are used as a starting point toward the development of specific inhibitors of histone deacetylases from the class of sirtuins.

Gate-variable light absorption and emission in a semiconducting carbon nanotube.

We investigate the gate field dependence of light absorption and emission of an individual, suspended semiconducting carbon nanotube using Raman and photoluminescence spectroscopies. We find a strong reduction in the absorption strength and a red shift of the E(33) state of the nanotube with increasing gate field. The photoluminescence from the E(11) state is quenched even stronger. We explain these observations in terms of field-doping and its effects on both the radiative and nonradiative decay rates of the excitons. Thus, gate field-induced doping constitutes an effective means of controlling the optical properties of carbon nanotube devices.

Energy dissipation in graphene field-effect transistors.

We measure the temperature distribution in a biased single-layer graphene transistor using Raman scattering microscopy of the 2D-phonon band. Peak operating temperatures of 1050 K are reached in the middle of the graphene sheet at 210 kW cm(-2) of dissipated electric power. The metallic contacts act as heat sinks, but not in a dominant fashion. To explain the observed temperature profile and heating rate, we have to include heat flow from the graphene to the gate oxide underneath, especially at elevated temperatures, where the graphene thermal conductivity is lowered due to umklapp scattering. Velocity saturation due to phonons with about 50-60 meV energy is inferred from the measured charge density via shifts in the Raman G-phonon band, suggesting that remote scattering (through field coupling) by substrate polar surface phonons increases the energy transfer to the substrate and at the same time limits the high-bias electronic conduction of graphene.

Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma.

OBJECTIVE: To evaluate the efficacy of pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy in patients with severe localized scleroderma (LS). DESIGN: A prospective, nonrandomized, open pilot study. SETTING: Dermatology department at a university hospital in Bochum, Germany. Patients Fifteen patients with histologically confirmed severe LS. Interventions Oral methotrexate (15 mg/wk) combined with pulsed intravenous methylprednisolone (1000 mg for 3 days monthly) for at least 6 months. MAIN OUTCOME MEASURES: Treatment outcome was evaluated by means of a clinical score, 20-MHz ultrasonography, and histopathologic analysis. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. RESULTS: One patient discontinued therapy. In most of the remaining 14 patients, significant elimination of all signs of active disease (inflammation) and remarkable softening of formerly affected sclerotic skin that resulted in a decrease of the mean +/- SD clinical score from 10.9 +/- 5.3 at the beginning to 5.5 +/- 2.5 at the end of therapy was observed (P < .001). Clinical improvement was confirmed by histologic and ultrasonographic assessments. No serious adverse effects were noted. CONCLUSIONS: These data suggest that pulsed high-dose corticosteroids combined with orally administered low-dose methotrexate therapy is beneficial and safe in the treatment of patients with LS. This treatment regimen should especially be considered for severe forms of LS in which conventional treatments have failed.

Pimecrolimus 1% cream for cutaneous lupus erythematosus.

Topical treatment of cutaneous lupus erythematosus usually includes potent glucocorticosteroids. However, prolonged use causes adverse side effects including skin atrophy as the foremost concern. In contrast to glucocorticosteroids, the anti-inflammatory and immunosuppressive macrolactam pimecrolimus has no atrophogenic potential. Affected areas of 11 patients with different forms of lupus erythematosus were treated with pimecrolimus 1% cream under semiocclusive conditions twice daily for 3 weeks. Skin involvement before and after therapy was assessed by means of a clinical score. In all patients, significant regression of skin lesions was observed after therapy (P <.001). This was an open and uncontrolled study on a limited number of cases. We suggest that pimecrolimus 1% cream could be an efficacious and safe treatment option for cutaneous lupus erythematosus.

Contact dermatitis and other skin conditions in instrumental musicians.

BACKGROUND: The skin is important in the positioning and playing of a musical instrument. During practicing and performing there is a permanent more or less intense contact between the instrument and the musician's skin. Apart from aggravation of predisposed skin diseases (e.g., atopic eczema or psoriasis) due to music-making, specific dermatologic conditions may develop that are directly caused by playing a musical instrument. METHODS: To perform a systematic review on instrument-related skin diseases in musicians we searched the PubMed database without time limits. Furthermore we studied the online bibliography "Occupational diseases of performing artist. A performing arts medicine bibliography. October, 2003" and checked references of all selected articles for relevant papers. RESULTS: The most prevalent skin disorders of instrumental musicians, in particular string instrumentalists (e.g., violinists, cellists, guitarists), woodwind players (e.g., flautists, clarinetists), and brass instrumentalists (e.g., trumpeters), include a variety of allergic contact sensitizations (e.g., colophony, nickel, and exotic woods) and irritant (physical-chemical noxae) skin conditions whose clinical presentation and localization are usually specific for the instrument used (e.g., "fiddler's neck", "cellist's chest", "guitar nipple", "flautist's chin"). Apart from common callosities and "occupational marks" (e.g., "Garrod's pads") more or less severe skin injuries may occur in musical instrumentalists, in particular acute and chronic wounds including their complications. Skin infections such as herpes labialis seem to be a more common skin problem in woodwind and brass instrumentalists. CONCLUSIONS: Skin conditions may be a significant problem not only in professional instrumentalists, but also in musicians of all ages and ability. Although not life threatening they may lead to impaired performance and occupational hazard. Unfortunately, epidemiological investigations have exclusively been performed on orchestra musicians, though the prevalence of instrument-related skin conditions in other musician groups (e.g., jazz and rock musicians) is also of interest. The practicing clinician should be aware of the special dermatologic problems unique to the musical instrumentalist. Moreover awareness among musicians needs to be raised, as proper technique and conditioning may help to prevent affection of performance and occupational impairment.

Pimecrolimus 1% cream for anogenital lichen sclerosus in childhood.

BACKGROUND: Lichen sclerosus is a chronic inflammatory disease with a predilection of the anogenital region. Because of the potential side effects of repeated local application of potent glucocorticosteroids, equally-effective, safer therapeutic options are required, especially in the treatment of children. CASE PRESENTATIONS: We report on the efficacy of twice-daily application of pimecrolimus 1% cream in four prepubertal girls (range of age: 4 to 9 years) who suffered from anogenital lichen sclerosus. After three to four-month treatment, all patients had almost complete clinical remission including relief from itch, pain and inflammation. Only minor improvement was observed for the white sclerotic lesions. No significant side effects have been observed. CONCLUSIONS: Topical pimecrolimus appears to be an effective and safe treatment for children with anogenital lichen sclerosus. The clinical benefits observed in the four patient presented particularly include relief of pruritus, pain and inflammation. Vehicle-controlled studies on a larger number of patients are now warranted to substantiate our promising findings, and to investigate long-term efficacy and safety of topical pimecrolimus in anogenital lichen sclerosus.

Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: case report.

BACKGROUND: Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. CASE PRESENTATION: We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. CONCLUSIONS: Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

Substrate-sensitive mid-infrared photoresponse in graphene.

We report mid-infrared photocurrent spectra of graphene nanoribbon arrays on SiO2 dielectrics showing dual signatures of the substrate interaction. First, hybrid polaritonic modes of graphene plasmons and dielectric surface polar phonons produce a thermal photocurrent in graphene with spectral features that are tunable by gate voltage, nanoribbon width, and light polarization. Second, phonon polaritons associated with the substrate are excited, which indirectly heat up the graphene, leading to a graphene photocurrent with fixed spectral features. Models for other commonly used substrates show that the responsivity of graphene infrared photodetectors can be tailored to specific mid-IR frequency bands by the choice of the substrate.

Photocurrent in graphene harnessed by tunable intrinsic plasmons.

Graphene's optical properties in the infrared and terahertz can be tailored and enhanced by patterning graphene into periodic metamaterials with sub-wavelength feature sizes. Here we demonstrate polarization-sensitive and gate-tunable photodetection in graphene nanoribbon arrays. The long-lived hybrid plasmon-phonon modes utilized are coupled excitations of electron density oscillations and substrate (SiO2) surface polar phonons. Their excitation by s-polarization leads to an in-resonance photocurrent, an order of magnitude larger than the photocurrent observed for p-polarization, which excites electron-hole pairs. The plasmonic detectors exhibit photo-induced temperature increases up to four times as large as comparable two-dimensional graphene detectors. Moreover, the photocurrent sign becomes polarization sensitive in the narrowest nanoribbon arrays owing to differences in decay channels for photoexcited hybrid plasmon-phonons and electrons. Our work provides a path to light-sensitive and frequency-selective photodetectors based on graphene's plasmonic excitations.

Tunable infrared plasmonic devices using graphene/insulator stacks.

The collective oscillation of carriers--the plasmon--in graphene has many desirable properties, including tunability and low loss. However, in single-layer graphene, the dependence on carrier concentration of both the plasmonic resonance frequency and magnitude is relatively weak, limiting its applications in photonics. Here, we demonstrate transparent photonic devices based on graphene/insulator stacks, which are formed by depositing alternating wafer-scale graphene sheets and thin insulating layers, then patterning them together into photonic-crystal-like structures. We show experimentally that the plasmon in such stacks is unambiguously non-classical. Compared with doping in single-layer graphene, distributing carriers into multiple graphene layers effectively enhances the plasmonic resonance frequency and magnitude, which is different from the effect in a conventional semiconductor superlattice and is a direct consequence of the unique carrier density scaling law of the plasmonic resonance of Dirac fermions. Using patterned graphene/insulator stacks, we demonstrate widely tunable far-infrared notch filters with 8.2 dB rejection ratios and terahertz linear polarizers with 9.5 dB extinction ratios. An unpatterned stack consisting of five graphene layers shields 97.5% of electromagnetic radiation at frequencies below 1.2 THz. This work could lead to the development of transparent mid- and far-infrared photonic devices such as detectors, modulators and three-dimensional metamaterial systems.

Raman and photocurrent imaging of electrical stress-induced p-n junctions in graphene.

Electrostatically doped graphene p-n junctions can be formed by applying large source-drain and source-gate biases to a graphene field-effect transistor, which results in trapped charges in part of the channel gate oxide. We measure the temperature distribution in situ during the electrical stress and characterize the resulting p-n junctions by Raman spectroscopy and photocurrent microscopy. Doping levels, the size of the doped graphene segments, and the abruptness of the p-n junctions are all extracted. Additional voltage probes can limit the length of the doped segments by acting as heat sinks. The spatial location of the identified potential steps coincides with the position where a photocurrent is generated, confirming the creation of p-n junctions.

Infrared spectroscopy of wafer-scale graphene.

We report spectroscopy results from the mid- to far-infrared on wafer-scale graphene, grown either epitaxially on silicon carbide or by chemical vapor deposition. The free carrier absorption (Drude peak) is simultaneously obtained with the universal optical conductivity (due to interband transitions) and the wavelength at which Pauli blocking occurs due to band filling. From these, the graphene layer number, doping level, sheet resistivity, carrier mobility, and scattering rate can be inferred. The mid-IR absorption of epitaxial two-layer graphene shows a less pronounced peak at 0.37 ± 0.02 eV compared to that in exfoliated bilayer graphene. In heavily chemically doped single-layer graphene, a record high transmission reduction due to free carriers approaching 40% at 250 µm (40 cm(-1)) is measured in this atomically thin material, supporting the great potential of graphene in far-infrared and terahertz optoelectronics.

Thermal infrared emission from biased graphene.

The high carrier mobility and thermal conductivity of graphene make it a candidate material for future high-speed electronic devices. Although the thermal behaviour of high-speed devices can limit their performance, the thermal properties of graphene devices remain incompletely understood. Here, we show that spatially resolved thermal radiation from biased graphene transistors can be used to extract the temperature distribution, carrier densities and spatial location of the Dirac point in the graphene channel. The graphene exhibits a temperature maximum with a location that can be controlled by the gate voltage. Stationary hot spots are also observed. Infrared emission represents a convenient and non-invasive characterization tool for graphene devices.

Carbon nanotube photo- and electroluminescence in longitudinal electric fields.

The photoluminescence of a partially suspended, semiconducting carbon nanotube that forms the active channel of a field-effect transistor is quenched and red-shifted upon application of a longitudinal electrical (source-drain) field. The quenching can be explained by a loss of oscillator strength and an increased Auger-like nonradiative decay of the E(11) exciton. The spectral shifts are due to drain-field-induced doping that leads to enhanced dielectric screening. Electroluminescence due to electron impact excitation of E(11) excitons is red-shifted and broadened with respect to the zero-field photoluminescence. A combination of screening and heating of the carbon nanotube can explain both spectral shift and broadening of the electrically induced light emission.

Photocurrent imaging and efficient photon detection in a graphene transistor.

We measure the channel potential of a graphene transistor using a scanning photocurrent imaging technique. We show that at a certain gate bias, the impact of the metal on the channel potential profile extends into the channel for more than one-third of the total channel length from both source and drain sides; hence, most of the channel is affected by the metal. The potential barrier between the metal-controlled graphene and bulk graphene channel is also measured at various gate biases. As the gate bias exceeds the Dirac point voltage, VDirac, the original p-type graphene channel turns into a p-n-p channel. When light is focused on the p-n junctions, an impressive external responsivity of 0.001 A/W is achieved, given that only a single layer of atoms are involved in photon detection.

Phonon populations and electrical power dissipation in carbon nanotube transistors.

Carbon nanotubes and graphene are candidate materials for nanoscale electronic devices. Both materials show weak acoustic phonon scattering and long mean free paths for low-energy charge carriers. However, high-energy carriers couple strongly to optical phonons, which leads to current saturation and the generation of hot phonons. A non-equilibrium phonon distribution has been invoked to explain the negative differential conductance observed in suspended metallic nanotubes, while Raman studies have shown the electrical generation of hot G-phonons in metallic nanotubes. Here, we present a complete picture of the phonon distribution in a functioning nanotube transistor including the G and the radial breathing modes, the Raman-inactive zone boundary K mode and the intermediate-frequency mode populated by anharmonic decay. The effective temperatures of the high- and intermediate-frequency phonons are considerably higher than those of acoustic phonons, indicating a phonon-decay bottleneck. Most importantly, inclusion of scattering by substrate polar phonons is needed to fully account for the observed electronic transport behaviour.