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The objective of this study was to evaluate the effects of nanoparticles (nanospheres and nanocapsules) of the promising antifungal 2-amino-thiophene (6CN10) and 6CN10 complexed with 2-hydroxypropyl-β-cyclodextrin (6CN10:HP-β-CD) in vitro and compared with free drug against Candida and Cryptococcus, using a microdilution method to measure susceptibility. The Candida and Cryptococcus clinical strains were identified using phenotypic methods and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). To measure in vitro antifungal susceptibility, we used microdilution trials. Serial drug or nanoparticle dilutions were prepared according to the CLSI M27-A3 guidelines. Anti-biofilm activity was verified for Cryptococcus neoformans. All Candida isolates were sensitive to the free drug (MIC = 41.66-333.33 μg/mL) and were able to grow even at the higher concentration tested for all 6CN10 nanoparticles. However, the Cryptococcus neoformans strains presented MIC values of 0.32-83.33 μg/mL for 6CN10 nanoparticles, and MIC values of 0.1-0.2 μg/mL for 6CN10:HP-β-CD nanoparticles, i.e., 3333 times more active than the free drug (MIC values 166.66-333.33 μg/mL), and presenting activity greater than that of the reference drug amphotericin B (MIC = 0.5-0.125 μg/mL). 6CN10:HP-β-CD nanosphere also showed high anti-biofilm potential. The in vitro study showed that the nanoparticles allowed better drug efficiency against Cryptococcus than did the free drug. These results suggest that 6CN10-loaded nanoparticles may become a future alternative for cryptococcosis and candidiasis therapy. In vivo experiments are essential prior to clinical use.

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV− and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV− group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV− (13 (8–27.5) vs. 2.5 (1–5.5); p

Isopulegol (ISOP) is a monoterpenoid alcohol presented in the essential oils of several plants that possesses therapeutic properties The aim of this work was prepare samples with ISOP and α- and β-cyclodextrins (α- and β-CD) through three different methods: physical mixture, paste method (PC) and slurry complexation (SC). In order to evaluate the formation of inclusion complexes, the techniques of differential scanning calorimetry, thermogravimetry/derivative thermogravimetry, fourier transform infrared spectroscopy, X-ray diffractometry (XRD), gas chromatography–mass spectrometry analyses (GC/MS), docking, nuclear magnetic resonance and scanning electron microscopy were considered. The analyses of the α-CD or β-CD/ISOP revealed the formation of a complex mainly through the PC and SC methods for α-CD and β-CD, respectively. XRD diffraction characteristics presented formation of a trend to new solid phase, which suggested the formation of inclusion complexes. The GC/MS demonstrated that the PC method was the best one to form complexation with α-CD (48.8 %). Concerning β-CD, the SC method exhibited the strongest complexation (68.3 %). Furthermore, the molecular theoretical docking study demonstrated that α-CD/ISOP inclusion complex formed a more stable complex than did the β-CD/ISOP inclusion complex.

This study evaluated three different methods for the formation of an inclusion complex between alpha- and beta-cyclodextrin (α- and β-CD) and limonene (LIM) with the goal of improving the physicochemical properties of limonene. The study samples were prepared through physical mixing (PM), paste complexation (PC), and slurry complexation (SC) methods in the molar ratio of 1:1 (cyclodextrin:limonene). The complexes prepared were evaluated with thermogravimetry/derivate thermogravimetry, infrared spectroscopy, X-ray diffraction, complexation efficiency through gas chromatography/mass spectrometry analyses, molecular modeling, and nuclear magnetic resonance. The results showed that the physical mixing procedure did not produce complexation, but the paste and slurry methods produced inclusion complexes, which demonstrated interactions outside of the cavity of the CDs. However, the paste obtained with β-cyclodextrin did not demonstrate complexation in the gas chromatographic technique because, after extraction, most of the limonene was either surface-adsorbed by β-cyclodextrin or volatilized during the procedure. We conclude that paste complexation and slurry complexation are effective and economic methods to improve the physicochemical character of limonene and could have important applications in pharmacological activities in terms of an increase in solubility.

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.

2-[(2,6-dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile), 5TIO1, is a new 2-aminothiophene derivative with a promising pharmacological activity. The aim of this work was to evaluate the potential anxiolytic effect of 5TIO1 in animal models. In the elevated plus-maze test, 5TIO1 (0.1, 1.0 and 10.0 mg/kg, i.p) increased the time of permanence and the number of entries in the open arms. In the light/dark box test, 5TIO1 at dose of 0.1 mg/kg (i.p) also showed anxiolytic-like effect indicated by an increase in the time spent in the light box, similar to diazepam 2.0 mg/kg (i.p). 5TIO1 groups did not change locomotor and coordination activities in open field and rotarod tests, respectively, when compared to vehicle. Dose dependent process was not observed and the anxiolytic effects demonstrated were not completely reversed by flumazenil 25 mg/kg (i.p). Our results suggest that 5TIO1 can bind with other receptors, besides the benzodiazepine site of the GABA receptor in mouse brain.

Magnesium sulfate (MgSO4) is used to treat and prevent eclamptic seizures, and several anticonvulsant drugs (e.g., sodium valproate) are clinically effective antimanic drugs. Psychostimulant-induced hyperlocomotion has been proposed as an animal model for the study of antimanic drugs. The present study evaluated the effects of MgSO4 and sodium valproate (as a positive control) on hyperlocomotion induced by methylphenidate in mice. Acute MgSO4 (300-400 mg/kg), but not sodium valproate (100-300 mg/kg), prevented the increase in locomotor activity induced by methylphenidate (5.0 mg/kg). In contrast, repeated treatment (14 days) with valproate (300 mg/kg), but not MgSO4 (400 mg/kg), blocked methylphenidate-induced hyperlocomotion. Thus, acute MgSO4 exerted antimanic-like effects in this animal model.

Range reduction is a crucial step for the accuracy in trigonometric functions evaluation. A new pipelined architecture to deal with range reduction for floating point representation is presented in this paper. The algorithm is based on a look-up table storing the corresponding powers of 2 mod A. The overall design has been optimized for a modulo equal to 2?, which is the most widely used due to trigonometric functions requirements. We provide an evaluation of different configurations and a full error propagation study which ensures an accuracy of one unit in the last place.