Q-S laser micro-drilling and multipass full-beam Q-S laser for tattoo removal - a case series.

The purpose of this study was to evaluate the safety and efficacy of a new combined method of Q-S laser-assisted tattoo removal. Ten patients with 13 professional, mostly mono-chromatic black tattoos were recruited. All tattoos received the same Q-S laser treatment sequence. An objective evaluation of tattoo clearing was assessed by careful analysis of a standardized collection of digital images taken from each tattoo, 2 months after each laser session, with the help of a custom-made pigment-fading percentage photographic ruler. The percentages of pigment clearance and side effects were evaluated by 4 independent dermatologists. Patient satisfaction and perceived discomfort during and post-procedure were evaluated according to specific scales. Clinical evaluators confirmed an average photographic pigment clearance of 97% after a median 4.85 treatment sessions. The Frac-Tat® method required 40% fewer sessions compared to those calculated by Kirby-Desai estimates. Photographic assessment of laser-exposed skin quality performed 2 months after tattoo clearing was considered almost comparable with untreated peripheral skin, confirming a very low side effect score. The Frac-Tat QS laser-assisted tattoo removal sequence used in our study showed a high degree of safety and efficiency, clearing exogenous pigments in a relatively few number of sessions. Preliminary ablative photo-acoustic fractional 1064-nm Q-S laser micro-drilling was considered an essential step in optimizing tattoo removal, increasing wavelength-independent micro-columnar clearing of deeper dermal exogenous pigments. Our preliminary observations also confirmed a significant improvement of tattoo procedure-induced micro-textural changes thanks to a tissue remodeling effect induced by the 1064-nm Q-S fractional laser photo-acoustic ablation.

Nonablative transurethral Erbium:YAG laser treatment for chronic prostatitis/chronic pelvic pain syndrome: A prospective comparative study.

AIMS: This prospective study aimed to compare the clinical outcomes between the use of Erbium:YAG (Er:YAG) laser in a nonablative mode, to the use of the pharmacological treatment of oral tadalafil for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: The laser group received two sessions of Erbium:YAG laser, administered intraurethrally in a long, nonablative train of long pulses (SMOOTH™ mode), applied at the level of the male prostatic urethra. Tadalafil group received oral tadalafil at a dose of 5 mg/day, consecutively for 2 months. Effectiveness was assessed using the International Prostate Symptom Score (IPSS) questionnaire, VAS (visual analogue scale) pain score, and maximum urethral flow at follow-up visits up to 12 months after initiating treatment. Adverse effects were recorded after each treatment and follow-up sessions. RESULTS: The results show a significant decrease in the IPSS score in both groups up to the 12-month follow-up. The increase in Q-max was evident up to 3-months follow-up in the tadalafil group and up to 6 months in the laser group. The decrease in the VAS pain score was also significant in both treatment groups, lasting up to 3 months in the tadalafil group and up to 6 months in the laser group. CONCLUSIONS: The nonablative Er:YAG SMOOTH™ laser seems to be a promising treatment for this widely occurring condition. More studies are needed to confirm its safety and efficacy.

Treating Vaginal Laxity Using Nonablative Er:YAG Laser: A Retrospective Case Series of Patients From 2.5 Years of Clinical Practice.

INTRODUCTION: Vaginal laxity drastically impairs women's quality of life, suggesting there is a need for effective noninvasive treatments. AIM: The aim was to retrospectively assess the effectiveness and safety of a nonablative Er:YAG IntimaLase laser procedure for vaginal laxity in patients treated in our clinical practice during a 2.5-year period. METHODS: Laser treatment for vaginal laxity was performed using an intravaginal nonablative Er:YAG laser. Effectiveness was assessed using a Patient Satisfaction Questionnaire and also by independent evaluation of before and after treatment photographs of the patients' introitus. The safety and tolerability of the procedure was monitored in all patients. MAIN OUTCOME MEASURE: The study showed an improvement of sexual gratification and improvement of vaginal tightness, as assessed by patients. The tightness of the introitus was also improved, as assessed by independent evaluators. RESULTS: As assessed by the Patient Satisfaction Questionnaire, we show that 92.7% of patients experienced improvement of sexual gratification after IntimaLase laser treatment. The results of the visual evaluation of the grade of laxity improvement in the introitus area, when open introitus photos were evaluated, show that 69% (n = 20/29) of patients had an improvement of laxity. Nonablative Er:YAG treatment seems to be an effective and safe treatment for vaginal laxity. As it is a noninvasive procedure, it should be considered before any vaginoplasty surgery. The study included all the patients treated in clinical practice and observed very few adverse effects. The results were comparable with other published data. Because it is a retrospective study, there is a lack of a control group. CONCLUSION: The results have confirmed that patients suffering from vaginal laxity can be effectively treated using the nonablative Er:YAG IntimaLase procedure without adverse effects. Mitsuyuki M, Stok U, Hreljac I. Treating Vaginal Laxity Using Nonablative Er:YAG Laser: A Retrospective Case Series of Patients From 2.5 Years of Clinical Practice. Sex Med 2020;8:265-273.

Minimally invasive, non-ablative Er:YAG laser treatment of stress urinary incontinence in women--a pilot study.

The study presents an assessment of mechanism of action and a pilot clinical study of efficacy and safety of the Er:YAG laser for the treatment of stress urinary incontinence (SUI). The subject of this study is a treatment of SUI with a 2940 nm Er:YAG laser, operating in a special SMOOTH mode designed to increase temperature of the vaginal mucosa up to maximally 60-65 °C without ablating the epidermis. Numerical modelling of the temperature distribution within mucosa tissue following an irradiation with the SMOOTH mode Er:YAG laser was performed in order to determine the appropriate range of laser parameters. The laser treatment parameters were further confirmed by measuring in vivo temperatures of the vaginal mucosa using a thermal camera. To investigate the clinical efficacy and safety of the SMOOTH mode Er:YAG laser SUI treatment, a pilot clinical study was performed. The study recruited 31 female patients suffering from SUI. Follow-ups were scheduled at 1, 2, and 6 months post treatment. ICIQ-UI questionnaires were collected as a primary trial endpoint. Secondary endpoints included perineometry and residual urine volume measurements at baseline and all follow-ups. Thermal camera measurements have shown the optimal increase in temperature of the vaginal mucosa following treatment of SUI with a SMOOTH mode Er:YAG laser. Primary endpoint, the change in ICIQ-UI score, showed clinically relevant and statistically significant improvement after all follow-ups compared to baseline scores. There was also improvement in the secondary endpoints. Only mild and transient adverse events and no serious adverse events were reported. The results indicate that non-ablative Er:YAG laser therapy is a promising minimally invasive non-surgical option for treating women with SUI symptoms.

Development of human cell biosensor system for genotoxicity detection based on DNA damage-induced gene expression.

BACKGROUND: Human exposure to genotoxic agents in the environment and everyday life represents a serious health threat. Fast and reliable assessment of genotoxicity of chemicals is of main importance in the fields of new chemicals and drug development as well as in environmental monitoring. The tumor suppressor gene p21, the major downstream target gene of activated p53 which is responsible for cell cycle arrest following DNA damage, has been shown to be specifically up-regulated by genotoxic carcinogens. The aim of our study was to develop a human cell-based biosensor system for simple and fast detection of genotoxic agents. METHODS: Metabolically active HepG2 human hepatoma cells were transfected with plasmid encoding Enhanced Green Fluorescent Protein (EGFP) under the control of the p21 promoter (p21HepG2GFP). DNA damage was induced by genotoxic agents with known mechanisms of action. The increase in fluorescence intensity, due to p21 mediated EGFP expression, was measured with a fluorescence microplate reader. The viability of treated cells was determined by the colorimetric MTS assay. RESULTS: The directly acting alkylating agent methylmethane sulphonate (MMS) showed significant increase in EGFP production after 48 h at 20 µg/mL. The indirectly acting carcinogen benzo(a)pyren (BaP) and the cross-linking agent cisplatin (CisPt) induced a dose- dependent increase in EGFP fluorescence, which was already significant at concentrations 0.13 µg/mL and 0.41 µg/mL, respectively. Vinblastine (VLB), a spindle poison that does not induce direct DNA damage, induced only a small increase in EGFP fluorescence intensity after 24 h at the lowest concentration (0.1 µg/mL), while exposure to higher concentrations was associated with significantly reduced cell viability. CONCLUSIONS: The results of our study demonstrated that this novel assay based on the stably transformed cell line p21HepG2GFP can be used as a fast and simple biosensor system for detection of genetic damage caused by chemical agents.

Organophosphorus pesticides enhance the genotoxicity of benzo(a)pyrene by modulating its metabolism.

Organophosphorus compounds (OPs) are widely used as pesticides. They act primarily as neurotoxins, but there is increasing evidence for secondary mechanisms of their toxicity. We have shown that the model OPs, methyl parathion (PT) and methyl paraoxon (PO), are genotoxic. Benzo(a)pyrene (BaP) is a widespread environmental genotoxin found in cigarette smoke, polluted air and grilled food. As people are constantly exposed to low concentrations of BaP and also to OPs, the aim of this study was to determine possible synergistic effects of PT and PO on BaP-induced genotoxicity. In the bacterial reverse mutation assay, PT and PO increased the number of BaP-induced mutations. The comet assay with human hepatoma HepG2 cells showed that BaP-induced DNA strand breaks were increased by PT but slightly decreased by PO. Using the acellular comet assay with UVC-induced DNA strand breaks, we observed a decrease in DNA migration, indicating that OPs cause cross-linking, thus interfering with comet assay results. In HepG2 cells the two OPs induced micronuclei formation at very low doses (0.01 microg/ml) and together with BaP, a more than additive increase of micronuclei was observed, confirming their co-genotoxic effect. We demonstrated for the first time that PT and PO modulate the metabolic activation of BaP. Addition of PT or PO increased aldo-keto reductase (AKR1C1/2) levels in the presence of BaP, while cytochrome 1A (CYP1A) mRNA expression and activity were decreased. Further, specific inhibition of CYP1A had no effect on BaP or OP+BaP-induced micronuclei, whereas inhibition of AKR1C dramatically decreased the number of micronuclei induced by BaP or OP+BaP. Based on these results we propose that co-genotoxicity results from OPs mediated modulation of BaP metabolism, favouring the induction of AKR1C enzymes known to catalyse the formation of DNA reactive BaP o-quinones and the production of reactive oxygen species.

Effects of model organophosphorous pesticides on DNA damage and proliferation of HepG2 cells.

Organophosphorous compounds (OPs) are commonly used pesticides. The primary mechanism of OP toxicity is the inhibition of acetylcholine esterase in the nervous system leading to a variety of acute and chronic effects. Recent studies have revealed several other targets of OPs that disturb noncholinergic biological systems. We investigated whether low concentrations of model OPs-methyl parathion (PT), methyl paraoxon (PO), and dimefox (DF)-induce DNA damage and/or affect cell proliferation in human hepatoma HepG2 cells. Genotoxicity of OPs was evaluated using the comet assay. The effect on cell proliferation was tested using the MTT assay and proliferation marker Ki-67 immunocytochemistry. The effects of OPs on mRNA expression of the DNA damage responsivegenes p53, p21, GADD45alpha, and MDM2 were determined using qRT-PCR. PT induced DNA damage at lower concentrations (1 microg/mL) than PO (100 microg/mL), whereas DF did not induce DNA damage. PT and PO caused a reduction of cell proliferation at their highest concentrations (100 microg/mL), while DF increased cell proliferation at all concentrations used (0.01-100 microg/mL). PT and PO upregulated expression of DNA damage responsive genes, while DF upregulated expression of p53, downregulated expression of p21, and had no effect on the expression of MDM2 and GADD45alpha. We conclude that PT and PO are genotoxic, while DF shows mitogenic activity. An important finding of this study is that PT had higher genotoxic potential than PO, which warrants for further investigations to correctly evaluate the hazards of exposure to these chemicals.

Detection of xenobiotic-induced DNA damage by the comet assay applied to human and rat precision-cut liver slices.

The comet assay is a simple and sensitive method for measuring DNA damage at the level of individual cells and is extensively used in genotoxicity studies. It is commonly applied to cultured cells. The aim of this study was to apply the comet assay for use in fresh liver tissue, where metabolic activity, all cell types and tissue architecture are preserved. The response of liver slices to genotoxic agents was tested with the reactive oxygen species generating tert-butyl hydroperoxide (tBOOH, 0.1-2 mM), [corrected] and the pro-carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 0.5-2 mM) and benzo(a)pyrene (BaP, 10-100 microM). Dose-dependent DNA damage was observed and compared to HepG2 cells. At non-cytotoxic concentrations of carcinogens, human liver slices were more sensitive to tBOOH than rat liver slices, while no significant difference was found for BaP and IQ. Human liver slices were more sensitive to IQ than HepG2 cells, equally sensitive to BaP and less to tBOOH. Control slices showed low levels of DNA damage, which did not increase during 24 h preservation (0 degrees C) or 48 h culturing (37 degrees C). In conclusion, the comet assay that we applied for measuring DNA damage in precision-cut liver slices is an useful tool to study genotoxic effects induced by various potential genotoxicants, allowing for detection of species differences in susceptibility to carcinogens.

Cathepsin L affects apoptosis of glioblastoma cells: a potential implication in the design of cancer therapeutics.

BACKGROUND: Previous studies indicate that Cathepsin L (CatL) is involved in brain tumour progression. Here, CatL in tumour cell invasion and apoptosis has been studied. MATERIALS AND METHODS: Human glioblastoma cell line U87 was transfected with CatL cDNA in sense and antisense orientations. The in vitro invasiveness was tested in modified Boyden chambers. Apoptosis was determined by fluorescent staining, caspase activity, and by Bax and Bcl-2 mRNA levels. RESULTS: Surprisingly, the invasiveness of U87 cells was not impaired by genetic down-regulation of CatL expression. In the CatL antisense clones, the apoptotic rate induced by either intrinsic or extrinsic stimuli was increased, whereas CatL sense transfection seemed to protect the cells from apoptosis. CONCLUSION: Increased chemoresistance of tumour cells may be associated with increased levels of CatL and may have potential application in gene therapy, which would augment the apoptosis of glioblastoma cells induced by chemotherapy.