Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant.

The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical Candida albicans strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of C. albicans in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.

Mitochondria-Targeted Curcumin: A Potent Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus with a Possible Intracellular ROS Accumulation as the Mechanism of Action.

Mitocurcumin (a triphenylphosphonium curcumin derivative) was previously reported as a selective antitumoral compound on different cellular lines, as well as a potent bactericidal candidate. In this study, the same compound showed strong antimicrobial efficacy against different strains of methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentration was identical for all tested strains (four strains of MRSA and one strain of methicillin-sensitive Staphylococcus aureus), suggesting a new mechanism of action compared with usual antibacterial agents. All tested strains showed a significant sensitivity in the low micromolar range for the curcumin-triphenylphosphonium derivative. This susceptibility was modulated by the menadione/glutathione addition (the addition of glutathione resulted in a significant increase in minimal inhibitory concentration from 1.95 to 3.9 uM, whereas adding menadione resulted in a decrease of 0.49 uM). The fluorescence microscopy showed a better intrabacterial accumulation for the new curcumin-triphenylphosphonium derivative compared with simple curcumin. The MitoTracker staining showed an accumulation of reactive oxygen species (ROS) for a S. pombe superoxide dismutase deleted model. All results suggest a new mechanism of action which is not influenced by the acquired resistance of MRSA. The most plausible mechanism is reactive oxygen species (ROS) overproduction after a massive intracellular accumulation of the curcumin-triphenylphosphonium derivative.

Therapeutic challenges in epidermal inclusion cysts with periocular localization: case reports.

Epidermal inclusion cysts in the periocular region are distinctive pathologies exhibiting varied clinical and radiological features, and they should be taken into consideration in the differential diagnosis of cystic lesions near the orbit. This article discusses the clinical and radiological details, along with the surgical results, of two individual cases of epidermal inclusion cysts, with different localization and without any preceding trauma, surgical history, or eyelid inflammation. In the first case, a substantial spherical structure closely connected to the tarsal plate was identified via excisional biopsy, whereas the second case involved a soft, oval tumor located at the outer right orbital corner, as determined clinically and validated through computed tomography. The histological examination showed cysts lined with a keratinized squamous layer, confirming an epidermoid cyst. The surgical removal of the cysts led to esthetically satisfactory outcomes in both cases. The particularity of the presented cases lies in the locations and considerable sizes of the tumors, which have complicated their surgical management. Such instances of epidermal inclusion cysts attached to the tarsus are rarely reported in the literature.

Surgical management of periocular squamous cell carcinoma: case report.

This report describes the case of a 72-year-old female patient admitted to the ophthalmology clinic for a large round-oval tumor with a long-standing keratotic lesion on her lower eyelid, without extending to the free margin of the eyelid. The tumor was excised with a margin in non-tumorous tissue, the nearest being 1 mm away from the tumor at the 12 o'clock position. The surgical process was complicated by the patient's treatment with the anticoagulant rivaroxaban, resulting in increased bleeding during surgery. The histopathological evaluation showed characteristics indicative of a well-differentiated squamous cell carcinoma, more specifically, the keratoacanthoma type. Consequently, it was necessary to extend the excision at the 12 o'clock position by an additional 3 mm. The procedure involved extensive removal of the impacted area and subsequent reconstruction with advancement flaps, supported by histological examination to ensure total excision. In cases of squamous cell carcinoma on the eyelid, multiple sequential excisions are often required to ensure complete removal within safe histological margins, achieving desirable functional and esthetic results.

A systematic review of orbital apex syndrome of odontogenic origin: Proposed algorithm for treatment.

Orbital apex syndrome (OAS) can be a rare, but severe complication of an odontogenic infection and has high morbidity and mortality. Antibacterial drugs are typically an appropriate treatment choice, but the most severe cases are fungal in nature and pose a tough challenge to the clinician. The aim of this study was to determine the predisposing factors, specific aspects in its management and the appropriate treatment strategy in order to improve patient outcome. A systematic review was conducted using PubMed, PubMed Central, Web of Science, and Scopus up to February 2020, based on the associations between dental extraction or infections and OAS. Of 721 papers found, 18 articles were considered eligible and presented in total 21 cases (13 fungal and eight bacterial infections). The information was organized into a diagnostic and treatment algorithm which included data extracted both from the included cases and updated literature of treatment efficacy studies. Immunosuppression (uncontrolled diabetes mellitus and chemotherapy) was found as an important predisposing factor particularly for fungal infections. In these cases, we suggest that early simultaneous approaches, including aggressive surgical procedures and systemic administration of amphotericin B, result in a better outcome. In conclusion, medical intervention success depends on aggressive treatment and multidisciplinary teamwork.