Penetration of Quantum Dot Particles Through Human Skin

The skin is a large and accessible area of the body, offering the possibility to be used as an alternative route for drug delivery. In the last few years strong progress has been made on the developing of nanoparticulate systems for specific applications. The interaction of such small particles with human skin and their possible penetration attracted some interest from toxicological as well as from drug delivery perspectives. As size is assumed to play a key role, the aim of the present work was to investigate the penetration profile of very small model particles (similar to 4 nm) into excised human skin under conditions chosen to mimic the in vivo situation. Possible application procedures such as massaging the formulation (5 to 10 minutes) were analyzed by non-invasive multiphoton- and confocal laser scanning microscopy (MPM, CLSM). Furthermore, the application on damaged skin was taken into account by deliberately removing parts of the stratum corneum. Although it was clearly observed that the mechanical actions affected the distribution pattern of the QDs on the skin surface, there was no evidence of penetration into the skin in all cases tested. QDs could be found in deeper layers only after massaging of damaged skin for 10 min. Taking these data into account, obtained on the gold standard human skin, the potential applications of nanoparticulate systems to act as carrier delivering drugs into intact skin might be limited and are only of interest for partly damaged skin.

Quantum-chemical, NMR and X-ray diffraction studies on (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane

Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, ""ecstasy"") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), 133LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the a-methyl, although these two forms interconvert freely in solution. (C) 2007 Elsevier Inc. All rights reserved.

Na,K-ATPase activity and epithelial interfaces in gills of the freshwater shrimp Macrobrachium amazonicum (Decapoda, Palaemonidae)

Diadromous freshwater shrimps are exposed to brackish water both as an obligatory part of their larval life cycle and during adult reproductive migration; their well-developed osmoregulatory ability is crucial to survival in such habitats. This study examines gill microsomal Na,K-ATPase (K-phosphatase activity) kinetics and protein profiles in the freshwater shrimp Macrobrachium amazonicum when in fresh water and after 10-days of acclimation to brackish water (21 parts per thousand salinity), as well as potential routes of Na(+) uptake across the gill epithelium in fresh water. On acclimation, K-phosphatase activity decreases 2.5-fold, Na,K-ATPase alpha-subunit expression declines, total protein expression pattern is markedly altered, and enzyme activity becomes redistributed into different density membrane fractions, possibly reflecting altered vesicle trafficking between the plasma membrane and intracellular compartments. Ultrastructural analysis reveals an intimately coupled pillar cell-septal cell architecture and shows that the cell membrane interfaces between the external medium and the hemolymph are greatly augmented by apical pillar cell evaginations and septal cell inviginations, respectively. These findings ire discussed regarding the putative movement of Na(+) across the pillar cell interfaces and into the hemolymph via the septal cells, powered by the Na,K-ATPase located in their invaginations. (C) 2008 Elsevier Inc. All rights reserved.

Hyaluronidase Behavior at the Air/Liquid and Air/Lipid Interfaces and Improved Enzymatic Activity by Its Immobilization in a Biomembrane Model

Bovine testicular hyalurphidase (BT-HAase), a tetrameric enzyme responsible for randomly hyaluronic acid, catalytic hydrolysis, was successfully immobilized on Langmuir- Blodgett films prepared with the sodium salt of dihexadacylphosphoric acid, (DHP-Zn(II)) ending with dipalmitoylphosphatidylcholine, DPPC. Data of protein, adsorption at the air-liquid interface by means of pendant drop shipe analysis and interaction of the protein with Langmuir monolayers of DPPC, using a Langmuir trough, have provided information. about the conditions to be used in the protein immobilization. The dynamic surface pressure curves obtained from pendant drop experiments for the enzyme in buffer solutions indicate that, within the range of concentration investigated in this study, the enzyme exhibits the largest induction time at 5 mu g L(-1) attributed to diffusion processes. Nevertheless, it seems that, at this concentration, the most probable conformation should be the one which occupies the smallest area at pi -> 0. The surface pressure (pi) area curves obtained for BT-HAase and mixed DPPC- BT-HAase monolayers reveal the presence of the enzyme at the air-lipid interface up to 45 mN m(-1). Tests of enzymatic activity, using hyaluronic acid, HA, as the substrate, showed an increase of activity compared to the homogeneous medium. A simplified model of protein insertion into the lipid matrix is used to explain the obtained results.

C(alpha)-HOLDER CLASSICAL SOLUTIONS FOR NON-AUTONOMOUS NEUTRAL DIFFERENTIAL EQUATIONS

In this paper we discuss the existence of alpha-Holder classical solutions for non-autonomous abstract partial neutral functional differential equations. An application is considered.

The Tausk controversy on the foundations of quantum mechanics: Physics, philosophy, and politics

In 1966 the Brazilian physicist Klaus Tausk (b. 1927) circulated a preprint from the International Centre for Theoretical Physics in Trieste, Italy, criticizing Adriana Daneri, Angelo Loinger, and Giovanni Maria Prosperi`s theory of 1962 on the measurement problem in quantum mechanics. A heated controversy ensued between two opposing camps within the orthodox interpretation of quantum theory, represented by Leon Rosenfeld and Eugene P. Wigner. The controversy went well beyond the strictly scientific issues, however, reflecting philosophical and political commitments within the context of the Cold War, the relationship between science in developed and Third World countries, the importance of social skills, and personal idiosyncrasies.

EEG-based Brain-Computer Interfaces: An Overview of Basic Concepts and Clinical Applications in Neurorehabilitation

Some patients are no longer able to communicate effectively or even interact with the outside world in ways that most of us take for granted. In the most severe cases, tetraplegic or post-stroke patients are literally `locked in` their bodies, unable to exert any motor control after, for example, a spinal cord injury or a brainstem stroke, requiring alternative methods of communication and control. But we suggest that, in the near future, their brains may offer them a way out. Non-invasive electroencephalogram (EEG)-based brain-computer interfaces (BCD can be characterized by the technique used to measure brain activity and by the way that different brain signals are translated into commands that control an effector (e.g., controlling a computer cursor for word processing and accessing the internet). This review focuses on the basic concepts of EEG-based BC!, the main advances in communication, motor control restoration and the down-regulation of cortical activity, and the mirror neuron system (MNS) in the context of BCI. The latter appears to be relevant for clinical applications in the coming years, particularly for severely limited patients. Hypothetically, MNS could provide a robust way to map neural activity to behavior, representing the high-level information about goals and intentions of these patients. Non-invasive EEG-based BCIs allow brain-derived communication in patients with amyotrophic lateral sclerosis and motor control restoration in patients after spinal cord injury and stroke. Epilepsy and attention deficit and hyperactive disorder patients were able to down-regulate their cortical activity. Given the rapid progression of EEG-based BCI research over the last few years and the swift ascent of computer processing speeds and signal analysis techniques, we suggest that emerging ideas (e.g., MNS in the context of BC!) related to clinical neuro-rehabilitation of severely limited patients will generate viable clinical applications in the near future.

Differences Between ""Classical"" Risk Factors for Infections Caused by Methicillin-Resistant Staphylococcus aureus (MRSA) and Risk Factors for Nosocomial Bloodstream Infections Caused by Multiple Clones of the Staphylococcal Cassette Chromosome mec Type IV MRSA Strain

OBJECTIVE. To identify risk factors associated with nosocomial bloodstream infections caused by multiple clones of the staphylococcal cassette chromosome mec (SCCmec) type IV strain of methicillin-resistant Staphylococcus aureus (MRSA). DESIGN. An unmatched case-control study (at a ratio of 1 : 2) performed during the period from October 2002 through September 2003. SETTING. A 2,000-bed tertiary care teaching hospital affiliated with the University of Sao Paulo in Sao Paulo, Brazil. METHODS. Case patients (n = 30) were defined either as patients who had a bloodstream infection due to SCCmec type IV strains of MRSA diagnosed at least 48 hours after hospital admission or as neonates with the infection who were born in the hospital. Control patients (n = 60) were defined as patients with SCCmec type III MRSA infection diagnosed at least 48 hours after hospital admission. Genes n = 60 encoding virulence factors were studied in the isolates recovered from case patients, and molecular typing of the SCCmec type IV MRSA isolates was also done by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS. In multivariate analysis, the following 3 variables were significantly associated with having a nosocomial bloodstream infection caused by SCCmec type IV strains of MRSA: an age of less than 1 year, less frequent use of a central venous catheter (odds ratio [OR], 0.07 [95% confidence interval {CI}, 0.02-0.28]; P = .001), and female sex. A second analysis was performed that excluded the case and Pp. 001 control patients from the neonatal unit, and, in multivariate analysis, the following variables were significantly associated with having a nosocomial bloodstream infection caused by SCCmec type IV strains of MRSA: less frequent use of a central venous catheter (OR, 0.12 [95% CI, 0.03-0.55]; P = .007), lower Acute Physiology and Chronic Health Evaluation II score on admission (OR, 0.14 [95% CI, 0.03-0.61];), less frequent surgery (OR, 0.21 [95% CI, 0.06-0.83];), and female sex (OR, 5.70 [95% CI, 1.32-24.66]; P =.020). P = .009 Pp. 025 Pp). Of the 29 SCCmec type IV MRSA isolates recovered from case patients, none contained the Panton-Valentine leukocidin, gamma-hemolysin, enterotoxin B or C, or toxic shock syndrome toxin-1. All of the isolates contained genes for the LukE-LukD leukocidin and alpha-hemolysin. Genes for enterotoxin A were present in 1 isolate, and genes for beta-hemolysin were present in 3 isolates. CONCLUSIONS. ""Classical"" risk factors do not apply to patients infected with the SCCmec type IV strain of MRSA, which is an important cause of nosocomial bacteremia. This strain infects a patient population that is less ill and has had less frequent invasive procedures than a patient population infected with the multidrug-resistant strain of SCCmec type III MRSA. We found that virulence factors were rare and that Panton-Valentine leukocidin was absent. There were multiple clones of the SCCmec type IV strain in our hospital. Children under 1 year of age were at a higher risk. There was a predominant clone ( sequence type 5) in this patient population.

Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer

Objectives: Viruses and turnout cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16(INK4a) molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type. Study design: Cervical biopsies (N = 74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n = 31), CIN2-3 (n = 19), and invasive cancer (n = 14) were evaluated alongside 10 normal cervical specimens. Results: HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR = 0.12, 95%CI: 0.0163-0.7899; p = 0.04). HLA-E expression increased with the progression of the lesion (chi(2)-test for trend = 4.01; p = 0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR = 11.25, 95%CI: 2.324-54.465; p = 0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16(INK4a) presented a good concordance (Kappa: 0.67). Conclusions: HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Renormalizing the kinetic energy operator in elementary quantum mechanics

In this paper, we consider solutions to the three-dimensional Schrodinger equation of the form psi(r) = u(r)/r, where u(0) not equal 0. The expectation value of the kinetic energy operator for such wavefunctions diverges. We show that it is possible to introduce a potential energy with an expectation value that also diverges, exactly cancelling the kinetic energy divergence. This renormalization procedure produces a self-adjoint Hamiltonian. We solve some problems with this new Hamiltonian to illustrate its usefulness.

Micromorphology of Resin-Dentin Interfaces Using One-Bottle Etch&Rinse and Self-Etching Adhesive Systems on Laser-Treated Dentin Surfaces: A Confocal Laser Scanning Microscope Analysis

Background and Objectives: This study evaluated the hybrid layer (HL) morphology created by three adhesive systems (AS) on dentin surfaces treated with Er:YAG laser using two irradiation parameters. Study Design: Occlusal flat dentin surfaces of 36 human third molars were assigned into nine groups (n = 4) according to the following ASs: one bottle etch&rinse Single Bond Plus (3M ESPE), two-step Clearfil Protect Bond (Kuraray), and all-in-one S3 Bond (Kuraray) self-etching, which were labeled with rhodamine B or fluorescein isothiocyanate dextran and were applied to dentin surfaces that were irradiated with Er:YAG laser at either 120 (38.7 J/cm(2)) or 200 mJ/pulse (64.5 J/cm(2)), or were applied to untreated dentin surfaces (control group). The ASs were light-activated following MI and the bonded surfaces were restored with resin composite Z250 (3M ESPE). After 24 hours of storage in vegetable oil, the restored teeth were vertically, serially sectioned into 1-mm thick slabs, which had the adhesive interfaces analyzed with confocal laser microscope (CLSM-LSM 510 Meta). CLSM images were recorded in the fluorescent mode from three different regions along each bonded interface. Results: Non-uniform HL was created on laser-irradiated dentin surfaces regardless of laser irradiation protocol for all AS, while regular and uniform HL was observed in the control groups. ""Stretch mark""-like red lines were found within the HL as a result of resin infiltration into dentin microfissures, which were predominantly observed in 200 mJ/pulse groups regardless of AS. Poor resin infiltration into peritubular dentin was observed in most regions of adhesive interfaces created by all ASs on laser-irradiated dentin, resulting in thin resin tags with neither funnel-shaped morphology nor lateral resin projections. Conclusion: Laser irradiation of dentin surfaces at 120 or 200 mJ/pulse resulted in morphological changes in HL and resin tags for all ASs evaluated in the study. Lasers Surg. Med. 42:662-670, 2010. (C) 2010 Wiley-Liss, Inc.