Ultra-short laser pulse generated by a microring resonator system for cancer cell treatment.

A microring resonator (MRRs) system incorporated with a add/drop filter is proposed in which ultra-short single, multi-temporal, and spatial optical soliton pulses are simulated and used to kill abnormal cells, tumors, and cancer. Chaotic signals are generated by a bright soliton pulse within a nonlinear MRRs system. Gold nanoparticles and ultra-short femtosecond/picosecond laser pulses' interaction holds great interest in laser nanomedicine. By using appropriate soliton input power and MRRs parameters, desired spatial and temporal signals can be generated over the spectrum. Results show that short temporal and spatial solitons pulse with FWHM = 712 fs and FWHM = 17.5 pm could be generated. The add/drop filter system is used to generate the high-capacity, ultra-short soliton pulses in the range of nanometer/second and picometer/second.

Acne vulgarism treatment using ultra-short laser pulse generated by micro- and nano-ring resonator system.

Acne vulgaris is adebilitating dermatologic disease, and is conventionally treated by laser therapy using a microring resonator system. An evolving understanding of laser-tissue interactions involving Propioni bacterium acneproducing porphyrins, and the development of lasers to target the sebaceous glands, has led to the development of an escalating number of laser light for acne treatment. The results show that the full width at half maximum of the proposed laser pulse of 0.15 nm can be generated using a microring resonator system. The power of the laser is 200 W and the wavelength laser is 1,032 nm, which is proposed as a treatment of acne vulgaris diseases.

Drug trapping and delivery for Alzheimer's diagnosis.

In this investigation, a new design based on a PANDA ring resonator as an optical trapping tool for tangle protein, molecular motor storage, and delivery is proposed. The optical vortices are generated and the trapping mechanism is controlled in the same way as the conventional optical tweezers. The trapping force is produced by a combination of the gradient field and scattering photons. The required molecular volume is trapped and moved dynamically within the molecular network. The tangle protein and molecular motor can be transported and delivered to the required destinations for Alzheimer's diagnosis by molecular buffer and bus network.

Generation of THz frequency using PANDA ring resonator for THz imaging.

In this study, we have generated terahertz (THz) frequency by a novel design of microring resonators for medical applications. The dense wavelength-division multiplexing can be generated and obtained by using a Gaussian pulse propagating within a modified PANDA ring resonator and an add/drop filter system. Our results show that the THz frequency region can be obtained between 40-50 THz. This area of frequency provides a reliable frequency band for THz pulsed imaging.

Interleukin-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions.

BACKGROUND: Keloid scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen and extracellular matrix (ECM) components. To date, the role of cytokines in keloid pathogenesis has not been completely unravelled. Interleukin (IL)-18 is a pro-inflammatory cytokine that plays important roles in wound healing, fibrogenesis and carcinogenesis. OBJECTIVES: Our aim was to study the role of the IL-18 system in keloid pathogenesis. MATERIALS AND METHODS: Expression and localization of IL-18 and its receptor (IL-18R) were investigated in normal skin and keloid tissues using Western blot and immunohistochemistry. We further studied the expression of the IL-18 system in normal and keloid-derived cell lines in a coculture model. RESULTS: Results from Western blot and immunohistochemistry revealed that IL-18, IL-18Rα and IL-18Rß expression was elevated in keloid tissue compared with normal skin tissue. Studies on the expression of IL-18 and its antagonist, IL-18 binding protein (IL-18BP), using a coculture model demonstrated severe IL-18/IL-18BP imbalance in keloid keratinocyte/keloid fibroblast (KK/KF) cocultures with significant elevation of bioactive IL-18 whereas IL-18BP levels remained the same. This overproduction of bioactive IL-18 in keloid cocultures could be due to increased caspase-1 and decreased caspase-3 expression in keloid tissue, as well as decreased soluble IL-10 levels observed in keloid cocultures. The important inductive effects of IL-18 on KFs were further underscored by the observation that exposure of KF to IL-18 resulted in increased collagen and ECM component synthesis, and increased secretion of profibrotic cytokines such as IL-6 and IL-8. Finally, the addition of phosphatidylinositol 3-kinase (PI3K), mitogen activation protein kinase (MAPK), specificity protein 1 (Sp1) and mammalian target of rapamycin (mTOR) inhibitors inhibited IL-18 secretion in keloid cocultures. CONCLUSIONS: The present study has proven that the IL-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. It also suggests a therapeutic potential of PI3K, MAPK, Sp1 and mTOR inhibitors in the treatment of keloid scarring.

The role of stem cell factor and c-KIT in keloid pathogenesis: do tyrosine kinase inhibitors have a potential therapeutic role?

BACKGROUND: Keloids are fibroproliferative disorders characterized by increased deposition of extracellular matrix components. Stem cell factor (SCF) and its receptor c-KIT are expressed in a wide variety of cells and have also been demonstrated to be important modulators of the wound healing process. OBJECTIVES: To examine the role of the SCF/c-KIT system in keloid pathogenesis. METHODS: Immunohistochemical staining and Western blot analyses were used to examine localization and expression of SCF and c-KIT in keloid and normal skin tissue. This was followed by the detection of SCF and c-KIT expression in fibroblasts cultured in vitro and fibroblasts exposed to serum. To investigate the effect of epithelial-mesenchymal interactions, a two-chamber system was employed in which keratinocytes on membrane inserts were cocultured with the fibroblasts. SCF and c-KIT expression levels in all cell extracts and conditioned media were assayed by Western blotting. In another set of experiments, the effect of imatinib (Glivec(®), Gleevec(®); Novartis Pharma AG, Basel, Switzerland) on keloid fibroblasts was examined. RESULTS: SCF and c-KIT were upregulated in keloid scar tissue and in cultured fibroblasts stimulated with serum, highlighting their importance in the initial phase of wound healing. We further demonstrated that epithelial-mesenchymal interactions, mimicked by coculture of keratinocytes and fibroblasts in vitro, not only stimulated secretion of the soluble form of SCF in keloid cocultures but also brought about shedding of the extracellular domain of c-KIT perhaps by upregulation of tumour necrosis factor-α converting enzyme which was also upregulated in keloid scars in vivo and keloid cocultures in vitro. In addition keloid cocultures expressed increased levels of phosphorylated c-KIT highlighting an activation of the SCF/c-KIT system. Finally, we demonstrated that imatinib, a tyrosine kinase inhibitor, may be a possible therapeutic agent for keloids. CONCLUSION: These data indicate that the SCF/c-KIT system plays an important role in scar pathogenesis, and underscore the role of imatinib as a key therapeutic agent in keloid scars.

Comparative proteomic analysis between normal skin and keloid scar.

BACKGROUND: Keloids are pathological scars and, despite numerous available treatment modalities, continue to plague physicians and patients. OBJECTIVES: Identification of molecular mediators that contribute to this fibrotic phenotype. METHODS: Two-dimensional gel electrophoresis, MALDI-TOF, Mascot online database searching algorithm and Melanie 5 gel analysis software were employed for comparative proteomic analysis between normal skin (NS) and keloid scar (KS) tissue extracts. RESULTS: Seventy-nine protein spots corresponding to 23 and 32 differentially expressed proteins were identified in NS and KS, respectively. Isoforms of heat shock proteins, gelsolin, carbonic anhydrase and notably keratin 10 were strongly expressed in NS along with manganese superoxide dismutase, immune components, antitrypsin, prostatic binding protein and crystalline. Various classes of proteins were found either to be present or to be upregulated in keloid tissue: (i) inflammatory/differentiated keratinocyte markers: S100 proteins, peroxiredoxin I; (ii) wound healing proteins: gelsolin-like capping protein; (iii) fibrogenetic proteins: mast cell ß-tryptase, macrophage migration inhibitory factor (MIF); (iv) antifibrotic proteins: asporin; (v) tumour suppressor proteins: stratifin, galectin-1, maspin; and (vi) antiangiogenic proteins: pigment epithelium-derived factor. Significant increases in expression of asporin, stratifin, galectin-1 and MIF were observed by Western blot analysis in KS. CONCLUSIONS: This work has identified differentially expressed proteins specific to KS tissue extracts which can potentially be used as specific targets for therapeutic intervention.

mTOR as a potential therapeutic target for treatment of keloids and excessive scars.

Keloid is a dermal fibroproliferative disorder characterized by excessive deposition of extracellular matrix (ECM) components such as collagen, glycoproteins and fibronectin. The mammalian target of rapamycin (mTOR) is a serine/theronine kinase which plays an important role in the regulation of metabolic processes and translation rates. Published reports have shown mTOR as regulator of collagen expression and its inhibition induces a decrease in ECM deposition. Our aim was to investigate the role of mTOR in keloid pathogenesis and investigate the effect of rapamycin on proliferating cell nuclear antigen (PCNA), cyclin D1, collagen, fibronectin and alpha-smooth muscle actin (alpha-SMA) expression in normal fibroblasts (NF) and keloid fibroblasts (KF). Tissue extracts obtained from keloid scar demonstrated elevated expression of mTOR, p70KDa S6 kinase (p70S6K) and their activated forms, suggesting an activated state in keloid scars. Serum stimulation highlighted the heightened responsiveness of KF to mitogens and the importance of mTOR and p70S6K during early phase of wound healing. Application of rapamycin to monoculture NF and KF, dose- and time-dependently downregulates the expression of cytoplasmic PCNA, cyclin D1, fibronectin, collagen and alpha-SMA, demonstrating the anti-proliferative effect and therapeutic potential of rapamycin in the treatment of keloid scars. The inhibitory effect of rapamycin was found to be reversible following recovery in the expression of proteins following the removal of rapamycin from the culture media. These results demonstrate the important role of mTOR in the regulation of cell cycle and the expression of ECM proteins: fibronectin, collagen and alpha-SMA.

Epithelial-mesenchymal interactions in keloid pathogenesis modulate vascular endothelial growth factor expression and secretion.

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis during the wound healing process. As epithelial-mesenchymal interactions have been shown to regulate a plethora of genes in wound healing, we hypothesized that these interactions might have a role in modulating VEGF expression and angiogenesis. A two chamber co-culture model was used, wherein normal and keloid keratinocytes and fibroblasts were physically separated by membrane inserts while allowing cytokine diffusion. Cell lysates obtained from keratinocytes co-cultured with fibroblasts demonstrated increased expression of VEGF. An enzyme-linked immunosorbent assay (ELISA) showed significant increase in VEGF expression in co-culture conditioned media compared with controls. Additionally, the conditioned medium from keloid keratinocyte and fibroblast co-cultures increased proliferation and formation of complex three-dimensional capillary-like structures in human umbilical vein endothelial cells, emphasising the importance of epithelial-mesenchymal interactions in the angiogenic process. Immunostaining of keloid tissue localized VEGF in the basal layer of the epidermis and also demonstrated higher blood vessel density than normal skin. Keloid tissue extract also demonstrated increased expression of VEGF compared with normal skin. It is likely that epidermal VEGF exerts significant paracrine control over the dynamics and expression profile of underlying dermal fibroblasts. Addition of the inhibitors WP631, mitoxantrone, and Rapamycin to keloid keratinocyte and fibroblast co-cultures, downregulated secreted VEGF expression in a dose-dependent manner, suggesting therapeutic potential for these compounds in the treatment of keloid scars.

Intrapulmonary concentrations of telithromycin: clinical implications for respiratory tract infections due to Streptococcus pneumoniae.

BACKGROUND: Antimicrobial efficacy is dependent on the ability of the agent to reach the site of infection. To assess the bronchopulmonary drug disposition of a novel ketolide, telithromycin (TEL), the epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations were utilized as a surrogate marker for lung penetration. METHODS: Adult subjects scheduled for diagnostic bronchoscopy received oral TEL 800 mg once daily for 5 days. Plasma and bronchoalveolar lavage (BAL) samples were collected 2, 8, 12, or 24 h after the last TEL dose. TEL concentrations in the ELF and AM were determined using a validated HPLC assay. ELF drug concentrations were calculated using the urea dilution method. RESULTS: Seventeen subjects with a mean age 65 +/- 13 years and a mean weight of 81 +/- 25 kg completed this open-label study. The median (range) TEL concentrations in plasma and ELF, respectively, were 1.09 mg/l (1.00-4.81) and 3.91 mg/l (2.64-9.59) at 2 h (n = 6), 0.48 and 1.09 mg/l at 8 h (n = 1), 0.65 mg/l (0.18-1.55) and 1.81 mg/l (0.61-10.0) at 12 h (n = 5), and 0.11 mg/l (0.09-0.24) and 0.69 mg/l (0.15-1.58) at 24 h (n = 5). The median AM concentrations obtained from these subjects were 53.35 mg/l at 2 h, 32.55 mg/l at 8 h, 65.96 mg/l at 12 h, and 26.43 mg/l at 24 h. Overall TEL was well tolerated. No discontinuation was required due to an adverse event. CONCLUSIONS: TEL displayed high intrapulmonary penetration with ELF concentrations exceeding that of plasma at all time points. AM intracellular concentrations were multiple times higher than in the ELF and plasma. These data support the clinical efficacy of TEL against intracellular and extracellular pathogens, particularly with Streptococcus pneumoniae having an MIC(90 )well below achievable concentrations at the site of infection.

The treatment of open tibial fractures and of tibial non-union with a novel external fixator.

We report the results of external fixation in 29 patients treated for tibial fractures and tibial non-union using a novel multi axial external fixator (MAXX) followed prospectively until bony union. The results of treatment were classified according to the Association for the Study and Application of the Method of Ilizarov (ASAMI). Overall, 13 patients had excellent bone results; 13 had good bone results; two had fair bone results, and 1 patient had poor bone results. Regarding functional results, 21 patients had excellent results; 6 obtained good results; none had fair results, and two had poor results. Acute patients did better functionally than chronic patients. This fixator is safe and versatile, although the indications for its use are very specific.

Molecular analysis of genetic differences between virulent and avirulent strains of Aeromonas hydrophila isolated from diseased fish.

Aeromonas hydrophila, a normal inhabitant of aquatic environments, is an opportunistic pathogen of a variety of aquatic and terrestrial animals, including humans. A. hydrophila PPD134/91 is defined as virulent whereas PPD35/85 is defined as avirulent on the basis of their different LD50 values in fish. Suppression subtractive hybridization (SSH) was used to identify genetic differences between these two strains. Sixty-nine genomic regions of differences were absent in PPD35/85, and the DNA sequences of these regions were determined. Sixteen ORFs encoded by 23 fragments showed high homology to known proteins of other bacteria. ORFs encoded by the remaining 46 fragments were identified as new proteins of A. hydrophila, showing no significant homology to any known proteins. Among these PPD134/91-specific genes, 22 DNA fragments (21 ORFs) were present in most of the eight virulent strains studied but mostly absent in the seven avirulent strains, suggesting that they are universal virulence genes in A. hydrophila. The PPD134/91-specific genes included five known virulence factors of A. hydrophila: haemolysin (hlyA), protease (oligopeptidase A), outer-membrane protein (Omp), multidrug-resistance protein and histone-like protein (HU-2). Another 47 DNA fragments (44 ORFs) were mainly present in PPD134/91, indicating the heterogeneity among motile aeromonads. Some of these fragments encoded virulence determinants. These included genes for the synthesis of O-antigen and type II restriction/modification system. The results indicated that SSH is successful in identifying genetic differences and virulence genes among different strains of A. hydrophila.

General dental practitioners' perceptions of removable prosthodontics in the undergraduate curriculum.

The undergraduate dental curriculum is undergoing rapid change and revision in dental schools worldwide. Decreasing edentulism, the advent of the clinical dental technician, and advances in technology (such as dental implantology) have led to changes in patient management and treatment options for general dental practitioners in New Zealand. The current undergraduate removable prosthodontic curriculum has seen very little change in past years at the School of Dentistry, University of Otago, and is under review to facilitate the teaching of general dental practice in the Final Year. A questionnaire-based survey of 150 general dental practitioners (response rate 74.6 percent) supported modification of the existing removable prosthodontics curriculum to improve its relevance to modern general dental practice. Integration of fixed and removable prosthodontic teaching was recommended.

[Clinical experience with fluconazole monotherapy in cryptococcal meningitis: report of four cases].

Four patients with cryptococcal meningitis have been treated with fluconazole in the past two years at the Department of Neurology, National Cheng Kung University Medical Center. There were three women and one man. Two patients had a history of anemia and one had undergone a splenectomy due to hypersplenism. Two patients were healthy before the onset of meningitis. After receiving fluconazole 300 mg per day for 8 to 13 weeks, three patients were cured without clinical evidence of recurrence during follow-up lasting from 2 to 17 months. One patient died from pneumothorax as a complication of subclavian vein cannulation. During the treatment course, there was no side effect except for one patient who had transient elevation of the GOT and GPT values which reversed spontaneously without a change in dosage. In the three successfully treated cases, the cryptococcal antigen titers began to decrease after the first week of treatment. Our preliminary experience shows that fluconazole alone is an effective and safe drug for the treatment of cryptococcal meningitis.