Combined laser and ozone therapy for onychomycosis in an in vitro and ex vivo model.
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ABSTRACT:
SUBMITTER: Fernandez J
PROVIDER: S-EPMC8244860 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Onychomycosis is a common fungal infection, afflicting some 10% of the adult population in industrialized countries. Aside from cosmetic concerns, onychomycosis can be the cause of toe and foot pain, as well as the underlying etiology for serious secondary bacterial infections and traumatic ulcerations. In select populations, such as diabetics, the latter conditions may even result in loss of all or part of the lower extremity. Thus, a simple, cost-effective and safe treatment for onychomycosis is highly desirable. Although both topical and oral systemic antifungal agents are available for this purpose, they are not always effective, carry some medical risks, are associated with potentially significant drug-drug interactions, and may be unacceptable to patient and healthcare provider alike. Physical modalities, such as laser therapy, therefore appear appealing. The question is whether laser treatment is sufficiently efficacious and safe to warrant the current high cost per treatment. The readily available literature on this controversy will be reviewed herein.
| S-EPMC5770012 | biostudies-literature
Project description:PurposeThere isscarce evidence to date on how temperature develops during holmium laser enucleation of the prostate (HoLEP). We aimed to determine the potential heat generation during HoLEP under ex vivo conditions.MethodsWe developed two experimental setups. Firstly, we simulated HoLEP ex vivo using narrow-neck laboratory bottles mimicking enucleation cavities and a prostate resection trainer. Seven temperature probes were placed at different locations in the experimental setup, and the heat generation was measured separately during laser application. Secondly, we simulated high-frequency current-based coagulation of the vessels using a roller probe.ResultsWe observed that the larger the enucleated cavity, the higher the temperature rises, regardless of the irrigation flow rate. The highest temperature difference with an irrigation flow was approximately + 4.5 K for a cavity measuring 100ccm and a 300 ml/min irrigation flow rate. The higher flow rate generates faster removal of the generated heat, thus cooling down the artificial cavity. Furthermore, the temperature differences at different irrigation flow rates (except at 0 ml/min) were consistently below 5 K. Within the resection trainer, the temperature increase with and without irrigation flow was approximately 0.5 K and 3.0 K, respectively. The mean depth of necrosis (1084 ± 176 µm) achieved by the roller probe was significantly greater when using 144 W energy.ConclusionCarefully adjusted irrigation and monitoring during HoLEP are crucial when evacuating the thermal energy generated during the procedure. We believe this study of ours provides evidence with the potential to facilitate clinical studies on patient safety.
| S-EPMC9236967 | biostudies-literature
Project description:Objective: The objective of this study was to assess the efficacy of non-thermal laser therapy for treating toenail onychomycosis. Design: This retrospective study analyzed the results of three nonrandomized, open-label studies. The device used was a 635nm/405nm dual-diode laser. Affected toenails were treated for 12 minutes weekly for 2 or 4 weeks. Setting: Treatments occurred in clinic and private office settings. Participants: Subjects with onychomycosis-infected toenails were enrolled. Measurements: Fifty great toenails were included in the analysis based on visually identifiable onychomycosis; thickened, discolored nail plate; and confirmed etiology of onychomycosis. Changes in the extent of clear nail bed was measured using multi-platform image manipulation software. The primary outcome measure was the percent of toenails attaining ≥3mm of clear nail growth during the six-month post-treatment period. Overall study success was defined as ≥60 percent of treated toenails meeting the individual success criteria. The secondary outcome measure was change in the length of clear nail bed. Results: Most treated toenails (67%) achieved individual treatment success. The extent of clear nail at baseline increased by a mean of 5.18 (4.76) mm after 6 months (p<0.0001). In addition, 89 percent of treated toenails demonstrated an increase in clear nail across the six-month study period. No adverse events were reported. Conclusion: Non-thermal laser therapy is safe and effective for increasing the extent of clear nail in onychomycosis-infected toenails following one weekly treatment for four weeks. ClinicalTrials.gov Identifier: NCT02588599.
| S-EPMC5479474 | biostudies-literature
Project description:ObjectivesGPR40 (FFAR1), a clinically proven anti-diabetes target, is a Gq-coupled receptor for long chain fatty acids (LCFA) stimulating insulin secretion directly and mediating a major part of the dietary triglyceride-induced secretion of the incretins GLP-1 and GIP. In phase-II studies the GPR40 agonist TAK-875 decreased blood glucose but surprisingly without stimulating incretins.Methods and resultsHere we find that GPR40 can signal through not only Gq and IP3 but also Gs and cAMP when stimulated with certain agonists such as AM-1638 and AM-5262 in contrast to the endogenous LCFA ligands and agonists such as TAK-875 and AM-837, which only signal through Gq. In competition binding against [3H]AM-1638 and [3H]L358 the Gq + Gs and the Gq-only agonists either competed for or showed positive cooperativity by increasing the binding of the two different radio-ligands, in opposite ways. Nevertheless, both the Gq-only and the Gq + Gs agonists all docked surprisingly well into the binding site for TAK-875 in the X-ray structure of GPR40. In murine intestinal primary cell-cultures the endogenous LCFAs and the Gq-only agonists stimulated GLP-1 secretion with rather poor efficacy as compared with the high efficacy Gq + Gs GPR40 agonists and a prototype GPR119 agonist. Similarly, in fasting both male and female mice the Gq + Gs agonists showed significantly higher efficacy than the Gq-only agonists in respect of increasing plasma GLP-1 and plasma GIP in a GPR40-dependent manner.ConclusionsIt is concluded that stimulation of GPR40 by endogenous LCFAs or by Gq-only synthetic agonists result in a rather limited incretin response, whereas Gq + Gs GPR40 agonists stimulate incretin secretion robustly.
| S-EPMC4314522 | biostudies-literature
Project description:BackgroundNew drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases.MethodWe report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found.ConclusionDrug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients.
| S-EPMC8123755 | biostudies-literature
Project description:Tumor plasticity is essential for adaptation to changing environmental conditions, in particular during the process of metastasis. In this study, we compared morphological and biochemical differences between LAN-1 neuroblastoma (NB) cells recovered from a subcutaneous xenograft primary tumor (PT) and the corresponding three generations of bone metastasis (BM I-III). Moreover, growth behavior, as well as the response to chemotherapy and immune cells were assessed. For this purpose, F-actin was stained, mRNA and protein expression assessed, and lactate secretion analyzed. Further, we measured adhesion to collagen I, the growth rate of spheroids in the presence and absence of vincristine, and the production of IL-6 by peripheral blood mononuclear cells (PBMCs) co-incubated with PT or BM I-III. Analysis of PT and the three BM generations revealed that their growth rate decreased from PT to BM III, and accordingly, PT cells reacted most sensitively to vincristine. In addition, morphology, adaption to hypoxic conditions, as well as transcriptomes showed strong differences between the cell lines. Moreover, BM I and BM II cells exhibited a significantly different ability to stimulate human immune cells compared to PT and BM III cells. Interestingly, the differences in immune cell stimulation corresponded to the expression level of the cancer-testis antigen MAGE-A3. In conclusion, our ex vivo model allows to analyze the adaption of tumor populations to different microenvironments and clearly demonstrates the strong alteration of tumor cell populations during this process.
| S-EPMC9954615 | biostudies-literature
Project description:Purpose: We aimed to evaluate the safety and effectiveness of applying an excimer laser in debulking human carotid atherosclerotic plaques by investigating the distal debris, plaque luminal gain, and micromorphology of the plaque surface. Methods: Eighteen plaque samples obtained from carotid endarterectomy (CEA) were randomly allocated to the excimer laser ablation (45 mJ/mm2, 25 Hz) alone group (group 1), balloon angioplasty (8 atm) alone group (group 2), and excimer laser ablation combined with balloon angioplasty group (group 3). Hematoxylin-eosin staining and Movat's pentachrome staining were performed on the collected particles to quantify the size and composition of the debris. The superficial micromorphological structure of the plaque lumen surface after device treatments was observed using a scanning electron microscope. Micro-CT, tissue sections, and pathological stainings were applied to the treated plaques. The plaque lumen and artery lumen were three-dimensionally reconstructed using clinical computed tomography angiography and the micro-CT images. Lumen enlargement was set as the main measurement of effectiveness. Results: Group 3 produced the highest luminal gain (5.40 ± 4.51 mm2), while the other two groups had gains of 4.05 ± 3.20 and 3.77 ± 2.55 mm2. Both devices caused disruptions to the plaque lumen surface. Laser ablation exposed the fibers under the endothelium and balloon angioplasty cracked the surface. The mean amounts were 3,611 ± 1,475.4 for group 1, 2,828 ± 1,266.7 for group 2, and 4,400 ± 2,567.9 for group 3. More than 90% of the distal debris was smaller than 10 μm. Group 2 produced the most debris with Feret (maximum caliper diameter) ≥ 40 μm; group 1 had the least. There was little difference in the contents of collagen and reticular fiber in the debris in each group, but a big difference was observed in the contents of fibrin and mucin. Conclusion: Excimer laser ablation could significantly increase the luminal gain of carotid plaque with high stenosis. Excimer laser combined with balloon angioplasty achieved the highest lumen enlargement. Our result also suggests that the embolic protection strategy needs to be renewed for the application of a plaque debulking device in the future.
| S-EPMC8488149 | biostudies-literature
Project description: Not available
| S-EPMC5820842 | biostudies-literature
Project description:In a sham-controlled double-blind trial, we aim to establish the efficacy and safety of the local application of laser therapy in patients with diabetes, onychomycosis and risk factors for diabetes-related foot complications. Onychomycosis leads to thickened and distorted nails, which in turn lead to increased local pressure. The combination of onychomycosis and neuropathy or peripheral arterial disease (PAD) increases the risk of developing diabetes-related foot complications. Usual care for high-risk patients with diabetes and onychomycosis is completely symptomatic with frequent shaving and clipping of the nails. No effective curative local therapies exist, and systemic agents are often withheld due to concerns for side effects and interactions.The primary aim is to evaluate the efficacy of four sessions of Nd:YAG 1064 nM laser application on the one-year clinical and microbiological cure rate in a randomized, double-blind, sham-controlled design with blinded outcome assessment. Mandatory inclusion criteria are diagnosis of diabetes, risk factors for developing foot ulcers defined as a modified Simm's classification score 1 or 2 and either neuropathy or PAD. A total of 64 patients are randomized to intervention or sham treatment performed by a podiatrist.This study will be the first double-blind study that investigates the effects of local laser therapy on onychomycosis, specifically performed in patients with diabetes with additional risk factors for foot complications.Clinical trials.gov as NCT01996995 , first received 22 November 2013.
| S-EPMC4381488 | biostudies-literature
Project description:An ex vivo approach to studying hepatic schistosomiasis used thick naive mouse liver sections and sterile culturing. This tissue is unfixed, unfrozen, and alive for subsequent in vitro studies. We have cultured and monitored these sections for up to 48 hrs noting unchanged gross hepato-cellular morphology, and no significant increases in hepatotoxicity as demonstrated by media liver enzyme concentrations. Liver slices were treated with soluble egg antigen from Schistosoma japonicum eggs and cultured for 48hrs. Transcriptional changes were then analysed by microarray. The gene expression profile of the naive mouse liver slices cultered with and without the additional of soluble egg antigen (SEA) from Schistosoma japonicum eggs. Microarray analysis was performed on cRNA synthesised from total RNA. The liver of female 6 week old C57BL/6 mice were removed and then sectioned at 250um thickness using a vibrotome. Sections were cultered at 37oC and 5%CO2 in in William’s Medium E containing 25 mM glucose, 10 mg/ml gentamycin and 10% FBS. SEA was added at 10ug/ml and sections sampled at timepoints 0, 4hr, 24hr and 48hrs. Illumina mouse ref8_V2 arrays were used and fold changes compared to whole intact, precut tissue.
2014-12-12 | E-GEOD-64071 | biostudies-arrayexpress