Development, optimization and characterization of nanoemulsion loaded with clove oil-naftifine antifungal for the management of tinea.

Tinea is a common superficial infection caused by keratinophylic fungi called dermatophytes. The objective of the current investigation was to develop and optimize a self-nanoemulsion drug delivery system (SENDDs) using clove oil loaded with naftifine (NF). Clove oil possesses good anti-inflammatory and antifungal properties that can support naftifine action. Box-Behnken designs were used to prepare plain and naftifine loaded SENDDs. The plain SENDDs were evaluated for their globule size. The medicated formulations (NF-CO-SENDDs) were characterized by measuring their globular size, ex vivo % NF permeated, level of interleukin-31 in rats, and antifungal activity. The optimum clove oil level was found to be 10-17%, while NF-CO-SENDDs formulations displayed globular sizes ranging from 119 to 310 nm. The statistical design confirmed the synergistic effect of clove oil and NF in the treatment of fungal infections, confirming that the anti-inflammatory effect of clove oil can counteract the side effects of NF. The optimized formulation composed of 14% clove oil, 12.5 mg Naftifine, and prepared with an Smix ratio equaling 3:1, exhibited good antifungal and anti-inflammatory activity, achieving up to 2-, 3-, 5.75-, and 2.74-fold increases in the amount of permeated NF, steady-state flux, permeability, and diffusion coefficients, respectively, compared with a commercial product. Moreover, the optimum formulation revealed an adequate zeta potential value of 28.31 ± 1.37 mV and showed reasonable stability with no or mild signs of skin sensitivity. Therefore, the designed nanoemulsions containing a combination of clove oil and naftifine could be considered promising delivery systems for the treatment of tinea.

Interstitial renal fibrosis due to multiple cisplatin treatments is ameliorated by semicarbazide-sensitive amine oxidase inhibition.

Elucidation of acute kidney diseases and disorders (AKD), including acute kidney injury (AKI), is important to prevent their progression to chronic kidney disease. Current animal AKI models are often too severe for use in evaluating human AKI. Therefore, new animal models of mild kidney injury are needed. Here a new clinically relevant animal model using multiple low doses of cisplatin (CP) was used to evaluate AKD. When 10 mg/kg CP was administered intraperitoneally once weekly for three times to L-type fatty acid-binding protein (L-FABP) transgenic mice, moderate renal interstitial fibrosis and tubule dilatation occurred, accompanied by brush-border loss. Urinary L-FABP, a promising biomarker of AKI, changed more drastically than blood urea nitrogen or creatinine. Preventing fibrosis in organs was also studied. Oral administration of a recently reported selective semicarbazide-sensitive amine oxidase inhibitor, PXS-4728A, for 1 week attenuated kidney injury and interstitial fibrosis compared with vehicle. Inhibition of renal lipid accumulation in semicarbazide-sensitive amine oxidase inhibitor-treated mice, together with reduced oxidative stress and L-FABP suppression in proximal tubules, suggested an antifibrotic effect of semicarbazide-sensitive amine oxidase inhibition in this CP-AKD model, a representative onco-nephrology. Thus, semicarbazide-sensitive amine oxidase inhibitors may be promising candidates for the prevention of chronic kidney disease in patients using CP to treat malignancy.

Oral therapeutic agents in fungal nail disease.

Oral griseofulvin has been the first-line drug in the therapy of dermatophyte onychomycosis for many years. Even when used long-term, it is effective in only about 30% of patients. Ketoconazole is not much more effective than griseofulvin in toenail infections, and there are significant problems with hepatotoxicity. Recently the triazoles, itraconazole and fluconazole, and the allylamine, terbinafine, were introduced and are believed to be potentially suitable for the oral treatment of fungal nail infection. Terbinafine is particularly effective in the treatment of dermatophyte onychomycosis, with a much shorter treatment period than griseofulvin. Cure rates of well over 80% have been noted in fingernail and toenail infection during treatment periods of 6 and 12 weeks, respectively. Itraconazole, 200 mg/day, has been noted in some studies to be similarly effective in the same treatment period. Few studies of fluconazole in nail infection have been carried out. These new agents appear to be safe, and results thus far suggest that they will soon overtake griseofulvin as the drug of choice in the oral therapy of nail infection.

[Naftifin--laboratory and clinical experience with a new antimycotic from the allylamine group]. / Naftifin--laboratorní a klinické zkusenosti s novým antimykotikem ze skupiny alylaminu.

The authors evaluated the effectiveness of naftifin on a broad spectrum of 42 types of agents causing mycoses. Using the microdilution method, the authors assessed minimal inhibiting concentrations (MIC) of this antimycotic agent in 107 clinical isolates. Naftifin displayed a selective antifungal activity: excellent sensitivity was found in dermatophytes (MIC 90% = 0.39 mg.l-1), Aspergillae were medium sensitive (MIC = 0.09-12.5 mg.l-1). The majority of yeasts and filamentous fungi from the group of Zygomycetes was resistant to naftifin. The therapeutic results in 57 subjects with dermatomycoses corresponded to the results of in vitro tests of the antimycotic agent. Most successful as treatment of dermatophytoses at extra-intertriginous sites and treatment of pityriasis versicolor; manifestation of candidoses were not affected. The commercial preparation used--Fetimin cream--is considered by the authors a suitable alternative of hitherto used local antimycotics, in particular preparations from the azole series.

Detection of the release of 5-hydroxyindole compounds in the hypothalamus and the n. raphe dorsalis throughout the sleep-waking cycle and during stressful situations in the rat: a polygraphic and voltammetric approach.

In the present work, voltammetric method combined with polygraphic recordings were used in animals under long-term chronic conditions; the extracellular concentrations of 5-hydroxyindole compounds (5-OHles) and in particular 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hypothalamus and in the nucleus Raphe Dorsalis (n.RD). The hypothesis that extracellular detection of 5-HIAA, in animals under physiological conditions, might reflect serotonin (5-HT) release is suggested by the following observations: serotoninergic neurons are reported to contain only monoamine oxidase type B (MAO-B);--an inhibitor of such an enzyme, MDL 72145 (1 mg/kg), fails to decrease the extracellular 5-HIAA peak 3 height:--MAO type A is contained in non-5-HT cells or neurons;--only the inhibitor of this last type of enzyme (Clorgyline 2.5 mg/kg) induces a complete disappearance of the voltammetric signal. The 5-HIAA measured in the extracellular space thus comes from the 5-HT released and metabolized outside the 5-HT neurons. Throughout the sleep-waking cycle, 5-OHles release occurs following two different modes: 1--during sleep, in the vicinity of the 5-HT cellular bodies in the n.RD; this release might come from dendrites and be responsible for the 5-HT neuronal inhibition occurring during sleep; 2--during waking, at the level of the axonal nerve endings impinging on the hypothalamus; this release might be related to the synthesis of "hypnogenic factors". Finally, we have observed that in the hypothalamus, 30 min. of immobilization-stress (IS) induces a larger increase of the voltammetric signal (+80%) than a painful stimulation of the same duration (+30%); the possible link between the 5-OHles release occurring in this area during an IS and the subsequent paradoxical sleep rebound is discussed.

The effects of chronic treatment with the 5-hydroxytryptamine uptake blocker zimelidine on central 5-hydroxytryptamine mechanisms. Evidence for the induction of a low affinity binding site for 5-hydroxytryptamine.

Male rats were treated with saline or the 5-hydroxytryptamine (5-HT) uptake inhibitor zimelidine (10 mumol/kg postoperatively) twice daily for a period of 14 days. The effects of this treatment on [5-3H]HT binding in the cerebral cortex and hypothalamus and on 5-HT synthesis were examined. Long-term treatment with zimelidine induced a low affinity site for 5-HT (Kd approximately 20 nM) in both areas and a reduced number of high affinity binding sites in the hypothalamus. Long-term zimelidine treatment did not attenuate the feed-back mediated inhibition of 5-HT synthesis. These findings suggest that chronic zimelidine treatment could result in a reduced activity at postsynaptic 5-HT receptor sites.