Effect of 1064-nm Q-switched Nd:YAG laser on invasiveness and innate immune response in keratinocytes infected with Candida albicans

Abstract

Candida albicans is an opportunistic pathogen commensal in the oral cavity, vagina, and healthy skin. Common therapeutic options for fungal infections are topical or systemic antifungal drugs. Recently, in cutaneous pathologies, lasers and light-based treatments have emerged showing few contraindications and minimal side effects. The Q-switched (Nd-YAG) laser at a wavelength of 1064 nm has been shown to be useful in dermatology, dentistry, and some other medical specialties. It is used to treat onychomycoses, warts, and wounds and in some other treatments. We analyzed the effect of Q-switched (Nd-YAG) laser 1064 nm on human keratinocytes infected with C. albicans. In particular, we evaluated the effect of laser on invasiveness of C. albicans and on inflammatory and protective response of HaCaT cells infected. The results obtained did not show inhibitory, fungicidal, or fungistatic effects of laser on yeast; in addition, laser did not affect HaCaT vitality. HaCaT cells infected with C. albicans and irradiated with laser showed a reduction of invasiveness of TNF-α and IL8 gene expression and an increase of immunomodulatory cytokines such as TGFβ. Furthermore, laser induces a significant over-expression of HSP70B (heat shock protein) and of HBD-2 (Human β defensin-2) in HaCaT infected with C. albicans, compared to the untreated control. The use of Q-switched Nd:YAG laser in skin mycosis caused by C. albicans reduces yeast invasiveness in keratinocytes, downregulates inflammatory activities, and facilitates cytoprotection and antimicrobial defense. Our results offer a promising therapeutic strategy in the management of skin candidiasis, also in combination with conventional therapies.

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Preparation and comparison of tacrolimus-loaded solid dispersion and self-microemulsifying drug delivery system by in vitro/in vivo evaluation

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Taotao Huo, Chun Tao, Minxin Zhang, Qinghong Liu, Bing Lin, Zhihong Liu, Jialiang Zhang, Meijing Zhang, Haiyue Yang, Jue Wu, Xinrong Sun, Qian Zhang, Hongtao Song
This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study.

Graphical abstract

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Does prophylactic ondansetron reduce norepinephrine consumption in patients undergoing cesarean section with spinal anesthesia?

Abstract

Purpose

Spinal anesthesia-induced hypotension (SAIH) during cesarean delivery is not rare and frequently leads to materno-fetal discrepancy and collapse. More recently, norepinephrine has been proposed for the prevention and treatment of SAIH with fewer tendencies to decrease heart rate and cardiac output. Ondansetron has been reported to reduce the incidence of SAIH in patients undergoing cesarean section. The aim of the present study was to assess the effect of prophylactic ondansetron on the incidence of SAIH, norepinephrine consumption, and adverse effects.

Methods

We recruited 108 parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia. The parturients were divided into two groups randomly. The first group (n = 54) received 8 mg ondansetron IV (group O) and the second group (n = 54) received the same volume (4 ml) of saline (group S), 5 min before spinal anesthesia. The incidence of hypotension, cumulative episodes of hypotension, total norepinephrine consumption, and adverse effects were recorded.

Results

There was no significant difference between the two groups in demographic data, parturient characteristics, and duration of surgery. No significant difference was found in the incidence of hypotension in the saline and ondansetron groups (p = 0.767). However, the cumulative episodes of hypotension and norepinephrine consumptions were significantly greater in group S than in group O (p = 0.009) (p = 0.009). There was also no significant difference in the incidence of adverse effects between the two groups.

Conclusion

Eight milligrams of intravenous ondansetron given 5 min before spinal anesthesia attenuated but did not prevent spinal anesthesia-induced hypotension in parturients undergoing elective cesarean delivery.

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Factors contributing to variation in the use of multimodality treatment in patients with gastric cancer: a Dutch population based study

Publication date: Available online 13 December 2017
Source:European Journal of Surgical Oncology
Author(s): N. Beck, L.A.D. Busweiler, M.G. Schouwenburg, M. Fiocco, A. Cats, F.E.M. Voncken, B.P.L. Wijnhoven, M.I. van Berge Henegouwen, M.W.J.M. Wouters, J.W. van Sandick
BackgroundSubstantial variation in the use of (neo)adjuvant treatment in patients with gastric cancer exists. The aim of this study was to identify underlying (organizational and process) factors associated with the use of perioperative therapy.Patients and methodsPatients with resectable gastric cancer who underwent surgery between 2012-2014 were selected from the Dutch Upper gastrointestinal Cancer Audit (DUCA). The proportion of perioperatively treated patients was defined per hospital. Five hospitals with the lowest percentage (LP group) and 5 hospitals with the highest percentage (HP group) of perioperative therapy were identified. In the selected hospitals additional information was obtained from patients' medical records using a structured list with predefined variables.ResultsIn total, 429 patients (231 in LP group, 198 in HP group) from 9 different hospitals were included. Perioperative therapy was given in 16.0% of patients in the LP group compared to 40.4% in the HP group. In the LP group, patients were enrolled in a clinical trial less frequently (10.8% versus 26.8%, P<0.001), and a higher percentage grade III-IV toxicity was observed during neoadjuvant treatment (25.7% versus 46.3%, P=0.007). Multivariable analysis showed that, besides known casemix factors, consultation with ≥3 upper GI specialists prior to treatment decision was positively associated with initiating perioperative therapy (OR 2.08, 95% CI 1.19 - 3.66).ConclusionResults of this study confirm considerable hospital variation in the use of perioperative therapy in patients with gastric cancer. Besides known casemix factors, use of perioperative therapy was associated with the level of involvement of multidisciplinary care.



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Prosthetic supply of facial defects: long-term experience and retrospective analysis on 99 patients

Abstract

Introduction

Defects in the head region may be caused by tumour treatments, injuries, as well as congenital malformations. The restoration of these defects that can be performed through reconstructive plastic surgery and/or prosthetic surgery occupies a high priority in the physical and psychological rehabilitation of the patient. The present study reports on long-term experience in supply of facial prosthesis.

Materials and methods

The medical records of 99 patients, who had been supplied with custom-made facial prostheses between 2001 and 2011, were evaluated retrospectively.

Results

There were 59 male (60%) and 40 (40%) female patients. The reason for prosthetic supplement was a tumour disease in 50 patients, congenital malformation in 39 patients, and trauma in 10 patients. Fifty-three patients were treated with ear prosthesis, twenty-seven patients were treated with eye prosthesis, and nineteen patients with nasal prosthesis. 82.8% of prosthetic supplies were designed as magnetic support prostheses. The most common complication was skin redness around the implants. 10% of patients suffered the loss of the osseointegrated implants.

Conclusion

The osseointegrated titanium implants with magnet support provide a reliable attachment for prosthesis and constitute a promising alternative to surgical reconstruction of complex facial defects.

http://ift.tt/2BjnURT

High PD-L1 expression indicates poor prognosis of HIV-infected patients with non-small cell lung cancer

Abstract

Background

The status of antitumor immunity represented by the expression of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and immune cell (IC) infiltration is unknown in HIV-infected patients with non-small cell lung cancer (NSCLC).

Methods

Fifteen HIV-infected patients with NSCLC were compared with 29 non-HIV-infected patients with NSCLC. Analysis of 13 propensity-score-matched patients in the two groups was also compared. The expression of PD-1/PD-L1 and tumor infiltration by CD4⁺, CD8⁺, and CD56⁺ immune cells were examined by immunohistochemistry; score of ≥ 2 was defined as positive.

Results

Although high PD-L1 expression in tumor cells was observed in HIV and non-HIV cohorts, the association of PD-1/PD-L1 was significant only in the HIV cohort. In overall as well as the propensity-matched analyses, HIV-infected patients with high PD-L1 expression showed shorter survival than HIV-infected patients with low PD-L1 expression; no significant difference was observed in this respect in the non-HIV cohort.

Conclusion

High PD-L1 expression in tumor tissue was associated with poor prognosis in HIV-infected NSCLC patients but not in non-HIV-infected NSCLC patients. These results suggest that antitumor immunity by PD-1/PD-L1 axis might be suppressed more in HIV-infected NSCLC patients as compared to their non-HIV-infected counterparts.

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Index des auteurs

Publication date: Available online 14 December 2017
Source:Revue des Maladies Respiratoires





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