Histological investigation in aging male and female gerbil prostates after prenatal exposure to pequi (Caryocar brasiliense Cambess) oil and 17α-ethinylestradiol.

The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.

Erythrina L. (Phaseoleae, Papilionoideae, Leguminosae) of Brazil: an updated nomenclatural treatment with notes on etymology and vernacular names.

Erythrina L. is a genus that comprises ca. 120 to 130 species distributed throughout the tropics and subtropics of the world. Linnaeus established the genus in Genera Plantarum (1737) and the first binomial name given to a Brazilian Erythrina was E.crista-galli L., described by himself in Mantissa Plantarum (1767). Vellozo proposed in Florae Fluminensis (1790-1881) the first treatment of the genus in Brazil, where he treated three species from the states of Rio de Janeiro and São Paulo. Martins and Tozzi proposed the most recent treatment in 2018, where the authors recognized 11 valid names and presented three new synonyms. Despite extensive efforts already made in the genus, previous works did not treat all names related to the valid ones for Brazilian Erythrina. The present work is the most comprehensive and up-to-date nomenclatural treatment for the genus in Brazil, covering all 84 related names found on digital nomenclatural databases. Here we analyze 64 protologues, update typification statuses, propose five new synonyms, 13 new lectotypes (11 first-step, two second-step) and one neotype, linking all protologues and type specimens with their corresponding available digital sources, and make additional notes on etymology and vernacular names.

Inhaled lipid nanocarriers for pulmonary delivery of glucocorticoids: Previous strategies, recent advances and key factors description.

In view of the strong anti-inflammatory activity of glucocorticoids (GC) they are used in the treatment of almost all inflammatory lung diseases. In particular, inhaled GC (IGC) allow high drug concentrations to be deposited in the lung and may reduce the incidence of adverse effects associated with systemic administration. However, rapid absorption through the highly absorbent surface of the lung epithelium may limit the success of localized therapy. Therefore, inhalation of GC incorporated into nanocarriers is a possible approach to overcome this drawback. In particular, lipid nanocarriers, which showed high pulmonary biocompatibility and are well known in the pharmaceutical industry, have the best prospects for pulmonary delivery of GC by inhalation. This review provides an overview of the pre-clinical applications of inhaled GC-lipid nanocarriers based on several key factors that will determine the efficiency of local pulmonary GC delivery: 1) stability to nebulization, 2) deposition profile in the lungs, 3) mucociliary clearance, 4) selective accumulation in target cells, 5) residence time in the lung and systemic absorption and 6) biocompatibility. Finally, novel preclinical pulmonary models for inflammatory lung diseases are also discussed.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

In vitro anti-melanoma activity of imiquimod in ultradeformable nanovesicles.

BACKGROUND: The wide spectrum of antitumoral mechanisms of imiquimod (IMQ), made it a good candidate for topical therapy of melanoma. However, physicochemical properties make IMQ formulation a difficult task. Solubility and skin penetration of IMQ are increased when loaded into ultradeformable nanovesicles. OBJECTIVE: Survey the in vitro anti-melanoma activity of IMQ loaded into two types of ultradeformable nanovesicles: archaeosomes (UDA-IMQ) (containing sn-2,3 ether-linked phytanyl saturated archaeolipids extracted from Halorubrum tebenquichense) and liposomes lacking archaeolipids (UDL-IMQ). METHODS: We prepared and structurally characterized UDA-IMQ and UDL-IMQ. Cytotoxicity was determined on human melanoma cells (SK-Mel-28) and keratinocytes (HaCaT cells) by MTT assay and LDH release. The cellular uptake was determined by flow cytometry. Apoptosis/necrosis induction was determined by fluorescence microscopy after double staining with YO-PRO-1® and propidium iodide. RESULTS: Neither IMQ nor IMQ-nanovesicles reduced the viability of HaCaT cells; but UDL-IMQ (371 nm, -24 mV ζ potential, 31 µg IMQ/mg lipids) and UDA-IMQ (216 nm, -32 mV ζ potential, 61 µg IMQ/mg lipids) showed time and concentration-dependent cytotoxicity on SK-Mel-28 that resulted between 4 and 33 folds higher than free IMQ, respectively. While both UDA-IMQ and UDL-IMQ retained 60% of IMQ against dilution, UDA-IMQ uptaken by SK-Mel-28 cells was nine-fold higher than UDL-IMQ. UDL-IMQ induced early apoptosis, but UDA-IMQ induced both apoptosis and necrosis on SK-Mel-28 cells. CONCLUSIONS: UDA-IMQ was innocuous to keratinocytes but was highly uptaken and induced apoptosis and necrosis on melanoma cells, being a candidate for future investigations as adjuvant topical anti-melanoma therapy.

Thymus vulgaris essential oil + tobramycin within nanostructured archaeolipid carriers: A new approach against Pseudomonas aeruginosa biofilms.

BACKGROUND: Pseudomonas aeruginosa biofilms in the respiratory tract of patients with an excessive inflammatory context are difficult to eradicate. New medicines that simultaneously target biofilms and inflammation should be developed. HYPOTHESIS: Co-delivery of Thymus vulgaris essential oil (EOT) and tobramycin (TB) by nanostructured archaeolipids carriers (NAC) could support nebulization as well as improve EOT and TB antioxidant, anti-inflammatory and antibiofilm activity. METHODS: NAC(EOT+TB) were prepared by loading EOT and TB in NAC having a compritol and miglyol core, covered with a shell of archaeolipids, extracted from the hyperhalophylic archaebacteria Halorubrum tebenquichense, and Tween 80. NAC(EOT+TB) were structurally characterized, including DSC thermograms, Raman spectra, TB release profile, EOT volatilization and in vitro antioxidant activity. In addition, stability upon nebulization, autoclaving and storage were assessed. The antibiofilm activity on P. aeruginosa PAO1 established biofilm of NAC(EOT+TB) and the cytotoxicity on human lung epithelial cells and macrophage were determined, as well as intracellular reactive oxygen species (ROS) production and cytokines release on LPS stimulated cells. RESULTS: NAC(EOT+TB) showed a size of 197 ± 16 nm with PdI of 0.3 ± 0.1 and ζ Potential of -38 ± 3 mV. Structural characterization suggested that EOT was trapped in the compritol-miglyol core and TB was distributed between the surface of nanoparticles and free in solution. NAC(EOT+TB) displayed a dual release profile of TB, a delayed release of EOT and improved EOTs in vitro antioxidant activity. While NAC(EOT+TB) preserved its structural features after nebulization, autoclaving and 18 months of storage, carriers without archaeolipids gelled at room temperature and showed a significant increase of size after the same storage time. Below cytotoxic concentration, NAC(EOT+TB) decreased bacteria viability and enhanced the disruption of established PAO1 biofilms compared to free TB and EOT. Also, the strong entrapment of EOT in NAC(EOT+TB) delayed its volatilization, decreased intracellular ROS production and maintained its anti-inflammatory activity in LPS stimulated cells. CONCLUSION: Combination of EOT + TB within NAC(EOT+TB) result in a stable and nebulizable formulation that enhanced the antioxidant and anti-biofilm activity of free ingredients, improved their ability to decrease intracellular ROS and provided anti-inflammatory activity, at non-cytotoxic concentrations on eukaryotic cells.

Cannabis-like activity of Zornia latifolia Sm. detected in vitro on rat cortical neurons: major role of the flavone syzalterin.

Zornia latifolia is a plant suspected to possess psychoactive properties and marketed as a marijuana substitute under the name 'maconha brava'. In this study, the effects of fractions obtained from a 2-propanol extract of aerial portions of the plant were determined by multielectrode array (MEA) analyses on cultured networks of rat cortical neurons. Lipophilic (ZL_lipo, mainly containing flavonoid aglycones), and hydrophilic (ZL_hydro, mainly containing flavonoid glycosides) fractions were initially obtained from the raw extract. ZL_lipo significantly inhibited mean firing rate (MFR) and mean bursting rate (MBR) of MEA recordings, while ZL_hydro induced no inhibition. Column chromatography separation of ZL_lipo yielded five fractions (ZL1-ZL5), among which ZL1 induced the strongest MFR and MBR inhibition. NMR and HPLC-MS analyses of ZL1 revealed the prevalence of the common flavonoids genistein (1) and apigenin (2) (in about a 1:1 ratio), and the presence of the rare flavone syzalterin (6,8-dimethylapigenin) (3) as a minor compound. Exposures of MEA to apigenin and genistein standards did not induce the MFR and MBR inhibition observed with ZL1, whereas exposure to syzalterin standard or to a 1:9 mixture syzalterin-genistein induced effects similar to ZL1. These inhibitory effects were comparable to that observed with high-THC hashish, possibly accounting for the plant psychoactive properties. Data indicate that Z. latifolia, currently marketed as a free herbal product, should be subjected to measures of control. In addition, syzalterin showed distinctive pharmacological properties, opening the way to its possible exploitation as a neuroactive drug.

Prenatal and pubertal exposure to 17α-ethinylestradiol disrupts folliculogenesis and promotes morphophysiological changes in ovaries of old gerbils (Meriones unguiculatus).

17α-Ethinylestradiol is an endocrine-disrupting chemical that make up most contraceptive pills and can be found in the environment. Exposure to ethinylestradiol in different development periods may promote changes in morphophysiological parameters of reproductive and endocrine organs. Considering that the effects of low doses (15 µg/kg/day) of ethinylestradiol in ovaries from 12-month-old female gerbils (Meriones unguiculatus) were investigated. Four experimental groups used were control (without treatment), EE/PRE (treated from the 18th to the 22nd gestational day), EE/PUB (treated from the 42nd to the 49th day of life), and EE/PRE-PUB (treated in the both periods). The animals were euthanized at 12 months. Testosterone and 17ß-estradiol levels were measured. The ovaries were stained with Hematoxylin and Eosin, Periodic Acid Schiff, and Gomori's Trichome. The follicles, corpus luteum, interstitial gland, lipofuscin, ovarian epithelium, and tunica albuginea were analyzed. Estradiol was higher in EE/PRE and EE/PUB groups, while testosterone was higher only in EE/PUB group. The main changes in follicle count occurred in EE/PUB and EE/PRE-PUB groups, with higher primordial follicle count and lower maturation of follicles. The corpus luteum was more evident in EE/PRE group. No differences were found in atretic follicles count. A higher area occupied by interstitial gland cells and lipofuscin deposit in these cells was noted in EE/PUB and EE/PRE-PUB groups. Higher epithelium height and thicker tunic albuginea were showed in treated groups. These results suggest that exposure to doses of EE2 in prenatal and pubertal periods of the development leads to morphological changes in senile ovaries.

The anti MRSA biofilm activity of Thymus vulgaris essential oil in nanovesicles.

BACKGROUND: Thymus vulgaris essential oil (T) could be an alternative to classical antibiotics against bacterial biofilms, which show increased tolerance to antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections. HYPOTHESIS: A nanovesicular formulation of T may chemically protect the structure and relative composition of its multiple components, potentially improving its antibacterial and antibiofilm activity. STUDY DESIGN: We prepared and structurally characterized T in two types of nanovesicles: nanoliposomes (L80-T) made of Soybean phosphatidylcholine (SPC) and Polysorbate 80 (P80) [SPC:P80:T 1:0.75:0.3 w:w], and nanoarchaeosomes (A80-T) made of SPC, P80 and total polar archaeolipids (TPA) extracted from archaebacteria Halorubrum tebenquichense [SPC:TPA:P80:T 0.5:0.50.75:0.7 w:w]. We determined the macrophage cytotoxicity and the antibacterial activity against Staphylococcus aureus ATCC 25,923 and four MRSA clinical strains. RESULTS: L80-T (Z potential -4.1 ±â€¯0.6 mV, ∼ 115 nm, ∼ 22 mg/ml T) and A80-T (Z potential -6.6 ±â€¯1.5 mV, ∼ 130 nm, ∼ 42 mg/ml T) were colloidally and chemically stable, maintaining size, PDI, Z potential and T concentration for at least 90 days. While MIC90 of L80-T was > 4 mg/ml T, MIC90 of A80-T was 2 mg/ml T for all S. aureus strains. The antibiofilm formation activity was maximal for A80-T, while L80-T did not inhibit biofilm formation compared to untreated control. A80-T significantly decreased the biomass of preformed biofilms of S. aureus ATCC 25,923 strain and of 3 of the 4 clinical MRSA isolates at 4 mg/ml T. It was found that the viability of J774A.1 macrophages was decreased significantly upon 24 h incubation with A80-T, L80-T and T emulsion at 0.4 mg/ml T. These results show that from 0.4 mg/ml T, a value lower than MIC90 and the one displaying antibiofilm activity, with independence of its formulation, T significantly decreased the macrophages viability. CONCLUSION: Overall, because of its lower MIC90 against planktonic bacteria, higher antibiofilm formation capacity and stability during storage, A80-T resulted better antibacterial agent than T emulsion and L80-T. These results open new avenues to explode the A80-T antimicrobial intracellular activity.

Correction to: Ultrastructure and secretion of glandular trichomes in species of subtribe Cajaninae Benth (Leguminosae, Phaseoleae).

In the original version of this article unfortunately some symbols did not appear in the plates caused by technical problems of the journal. We apologize for any inconvenience caused.

Novel imiquimod nanovesicles for topical vaccination.

Development of needle and pain free noninvasive immunization procedures is a top priority for public health agencies. In this work the topical adjuvant activity of the immunomodulator imiquimod (IMQ) carried by ultradeformable archaeosomes (UDA2) (nanovesicles containing sn-2,3 ether linked phytanyl saturated archaeolipids) was surveyed and compared with that of ultradeformable liposomes lacking archaeolipids (UDL2) and free IMQ, using the model antigen ovalbumin and a seasonal influenza vaccine in Balb/c mice. UDA2 (250 ± 94 nm, -26 ± 4 mV Z potential) induced higher IMQ accumulation in human skin and higher production of TNF-α and IL-6 by macrophages and keratinocytes than free IMQ and UDL2. Mixed with ovalbumin, UDA2 was more efficient at generating cellular response, as measured by an increase in serum IgG2a and INF-γ production by splenocytes, compared with free IMQ and UDL2. Moreover, mixed with a seasonal influenza vaccine UDA2 produced same IgG titers and IgG2a/IgG1 isotypes ratio (≈1) than the subcutaneously administered influenza vaccine. Topical UDA2 however, induced highest stimulation index and INF-γ levels by splenocytes. UDA2 might be a promising adjuvant for topical immunization, since it produced cell-biased systemic response with ≈ 13-fold lower IMQ dose than the delivered as the commercial IMQ cream, Aldara.

Ultrastructure and secretion of glandular trichomes in species of subtribe Cajaninae Benth (Leguminosae, Phaseoleae).

The subtribe Cajaninae of papilionoid legumes has a pantropical distribution and comprises approximately 490 species. These species have diversified throughout dry environments where there are high temperatures and strong light. The subtribe stands out because all its representatives have vesicular glands. In addition, bulbous-based and capitate trichomes are important secretory structures present in all genera of the Cajaninae. We analyzed the ultrastructure and histochemistry of these glandular trichome types in leaflets of the three species of the subtribe. Using transmission electron microscopy and histochemical analyses, we link the glandular secretions to subcellular structures. We here report for the first time the type of exudate and ultrastructure of the glands of subtribe Cajaninae. Terpenoids and phenolics were confirmed by histochemistry tests, and we observed that the organelles responsible for biosynthesis of oils are the most representative in these glands. Each glandular trichome showed particular ultrastructural features compatible with the compounds produced. We suggest that these glandular trichomes, with their respective exudates, act in defense against herbivory and against possible damage by ultraviolet radiation.

Test-Retest of Long Latency Auditory Evoked Potentials (P300) with Pure Tone and Speech Stimuli

Abstract Introduction Long latency auditory evoked potentials, especially P300, have been used for clinical evaluation of mental processing. Many factors can interfere with Auditory Evoked Potential - P300 results, suggesting large intra and inter-subject variations. Objective The objective of the study was to identify the reliability of P3 components (latency and amplitude) over 4-6 weeks and the most stable auditory stimulus with the best test-retest agreement. Methods Ten normal-hearing women participated in the study. Only subjects without auditory processing problems were included. To determine the P3 components, we elicited long latency auditory evoked potential (P300) by pure tone and speech stimuli, and retested after 4-6 weeks using the same parameters. We identified P300 latency and amplitude by waveform subtraction. Results We found lower coefficient of variation values in latency than in amplitude, with less variability analysis when speech stimulus was used. There was no significant correlation in latency measures between pure tone and speech stimuli, and sessions. There was a significant intrasubject correlation between measures of latency and amplitude. Conclusion These findings show that amplitude responses are more robust for the speech stimulus when compared with its pure tone counterpart. The P300 indicated stability for latency and amplitudemeasures when the test-retest was applied. Reliability was higher for amplitude than for latency, with better agreement when the pure tone stimulus was used. However, further research with speech stimulus is needed to clarify how these stimuli are processed by the nervous system.

Test-Retest of Long Latency Auditory Evoked Potentials (P300) with Pure Tone and Speech Stimuli.

Introduction Long latency auditory evoked potentials, especially P300, have been used for clinical evaluation of mental processing. Many factors can interfere with Auditory Evoked Potential - P300 results, suggesting large intra and inter-subject variations. Objective The objective of the study was to identify the reliability of P3 components (latency and amplitude) over 4-6 weeks and the most stable auditory stimulus with the best test-retest agreement. Methods Ten normal-hearing women participated in the study. Only subjects without auditory processing problems were included. To determine the P3 components, we elicited long latency auditory evoked potential (P300) by pure tone and speech stimuli, and retested after 4-6 weeks using the same parameters. We identified P300 latency and amplitude by waveform subtraction. Results We found lower coefficient of variation values in latency than in amplitude, with less variability analysis when speech stimulus was used. There was no significant correlation in latency measures between pure tone and speech stimuli, and sessions. There was a significant intrasubject correlation between measures of latency and amplitude. Conclusion These findings show that amplitude responses are more robust for the speech stimulus when compared with its pure tone counterpart. The P300 indicated stability for latency and amplitude measures when the test-retest was applied. Reliability was higher for amplitude than for latency, with better agreement when the pure tone stimulus was used. However, further research with speech stimulus is needed to clarify how these stimuli are processed by the nervous system.

Topical vaccination with super-stable ready to use nanovesicles.

Ultradeformable archaeosomes (UDA) are nanovesicles made of total polar archaeolipids (TPA) from the archaea Halorubrum tebenquichense, soybean phosphatidylcholine and sodium cholate (3:3:1w/w). Fresh dispersions of UDA including different type of antigens are acknowledged as efficient topical vaccination agents. UDA dispersions however, if manufactured for pharmaceutical use, have to maintain colloidal stability upon liposomicidal processes such as sterilization and lyophilization (SLRUDA), needed to extend shelf life during storage. The remaining capacity of SLRUDA to act as adjuvants was therefore tested here for the first time. Another unexplored issue addressed here, is the outcome of replacing classical antigen inclusion into nanovesicles by their physical mixture. Our results showed that UDA behaved as super-stable nanovesicles because of its high endurance during heat sterilization and storage for 5 months at 40°C. The archaeolipid content of UDA however, was insufficient to protect it against lyophilization, which demanded the addition of 2.5% v/v glycerol plus 0.07% w/v glucose. No significant differences were found between serum anti-ovalbumin (OVA) IgG titers induced by fresh or SLRUDA upon topical application of 4 weekly doses at 600µg lipids/75µg OVA to Balb/c mice. Finally, SLRUDA mixed with OVA elicited the same Th2 biased plus a non-specific cell mediated response than OVA encapsulated within UDA. Concluding, we showed that TPA is key component of super-stable nanovesicles that confers resistance to heat sterilization and to storage under cold-free conditions. The finding of SLRUDA as ready-to-use topical adjuvant would lead to simpler manufacture processing and cheaper products. .

Ultradeformable Archaeosomes for Needle Free Nanovaccination with Leishmania braziliensis Antigens.

Total antigens from Leishmania braziliensis promastigotes, solubilized with sodium cholate (dsLp), were formulated within ultradeformable nanovesicles (dsLp-ultradeformable archaeosomes, (dsLp-UDA), and dsLp-ultradeformable liposomes (dsLp-UDL)) and topically administered to Balb/c mice. Ultradeformable nanovesicles can penetrate the intact stratum corneum up to the viable epidermis, with no aid of classical permeation enhancers that can damage the barrier function of the skin. Briefly, 100 nm unilamellar dsLp-UDA (soybean phosphatidylcholine: Halorubrum tebenquichense total polar lipids (TPL): sodium cholate, 3:3:1 w:w) of -31.45 mV Z potential, containing 4.84 ± 0.53% w/w protein/lipid dsLp, 235 KPa Young modulus were prepared. In vitro, dsLp-UDA was extensively taken up by J774A1 and bone marrow derive cells, and the only that induced an immediate secretion of IL-6, IL-12p40 and TNF-α, followed by IL-1ß, by J774A1 cells. Such extensive uptake is a key feature of UDA ascribed to the highly negatively charged archaeolipids of the TPL, which are recognized by a receptor specialized in uptake and not involved in downstream signaling. Despite dsLp alone was also immunostimulatory on J774A1 cells, applied twice a week on consecutive days along 7 weeks on Balb/c mice, it raised no measurable response unless associated to UDL or UDA. The highest systemic response, IgGa2 mediated, 1 log lower than im dsLp Al2O3, was elicited by dsLp-UDA. Such findings suggest that in vivo, UDL and UDA acted as penetration enhancers for dsLp, but only dsLp-UDA, owed to its pronounced uptake by APC, succeeded as topical adjuvants. The actual TPL composition, fully made of sn2,3 ether linked saturated archaeolipids, gives the UDA bilayer resistance against chemical, physical and enzymatic attacks that destroy ordinary phospholipids bilayers. Together, these properties make UDA a promising platform for topical drug targeted delivery and vaccination, that may be of help for countries with a deficient healthcare system.

Topical amphotericin B in ultradeformable liposomes: Formulation, skin penetration study, antifungal and antileishmanial activity in vitro.

Aiming to improve the topical delivery of AmB to treat cutaneous fungal infections and leishmaniasis, ultradeformable liposomes containing amphotericin B (AmB-UDL) were prepared, and structural and functional characterized. The effect of different edge activators, phospholipid and AmB concentration, and phospholipid to edge activator ratio on liposomal deformability, as well as on AmB liposomal content, was tested. Liposomes having Tween 80 as edge activator resulted of maximal deformability and AmB/phospholipid ratio. These consisted of AmB-UDL of 107±8nm diameter, 0.078-polydispersity index and -3±0.2mV Z potential, exhibiting monomeric AmB encapsulated in the bilayer at a 75% encapsulation efficiency. After its cytotoxicity on keratinocytes (HaCaT cells) and macrophages (J774 cells) was determined, the in vitro antifungal activity of AmB-UDL was assayed. It was found that fungal strains (albicans and non-albicans Candida ATCC strains and clinical isolates of C. albicans) were more sensitive to AmB-UDL than mammal cells. Minimum inhibitory concentration values for AmB-UDL were 5-24 and 24-50 times lower than IC50 for J774 and HaCaT cells, respectively. AmB-UDL at 1.25µg/ml also displayed 100 and 75% anti- Leishmania braziliensis promastigote and amastigote activity, respectively. Finally, upon 1h of non-occlusive incubation, the total accumulation of AmB in human skin was 40 times higher when applied as AmB-UDL than as AmBisome. AmB-UDL provided a profound AmB penetration toward deep epithelial layers, achieved without classical permeation enhancers. Because of that, topical treatments of cutaneous fungal infection and leishmaniasis with AmB-UDL may be regarded of potential of clinical significance.

Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes.

In this work, the in vitro anti-Leishmania activity of photodynamic liposomes made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that while ZnPcUDLs and ZnPcALs (130 nm mean diameter and -35 mV zeta potential) were innocuous against promastigotes, a low concentration (0.01 µM ZnPc and 7.6 µM phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm(2)) eliminated L. braziliensis amastigotes from J774 macrophages, without reducing the viability of the host cells. In such conditions, ZnPcALs were harmless for J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells. Therefore, topical photodynamic treatment would not likely affect skin-associated lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher delivery of ZnPc and the multiple (caveolin- and clathrin-dependent plus phagocytic) intracellular pathway followed by ZnPc would have been the reason for the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of photodynamic liposomal ZnPc was improved by TPA-containing liposomes.

Relação entre dados coletados na anamnese e distúrbio do processamento auditivo / Relationship between data collected during the interview and auditory processing disorder

Objetivo o objetivo deste trabalho foi tentar relacionar dados da avaliação do processamento auditivo com os dados coletados na anamnese de crianças, adolescentes e jovens. Método foram analisadas as informações dos prontuários de 51 pacientes, de ambos os sexos, com idade de 5 a 20 anos, atendidos no Serviço de Avaliação do Processamento Auditivo, da UNIESP. Os aspectos observados na anamnese foram: dificuldades escolares, presença de depressão/desmotivação, uso de medicamentos, necessidade de acompanhamento psicológico ou psicopedagógico, e problemas de atenção e memória. Resultados foram encontrados 86% dos casos com dificuldades escolares, 43% faziam acompanhamento psicológico ou psicopedagógico, 37% apresentavam problemas de atenção e memória, e 33% faziam uso de medicamentos. Nenhum desses sintomas, porém, puderam ser associados com alterações no processamento temporal (ordenação e resolução) e reconhecimento de sons não verbais sobrepostos em escuta dicótica (atenção seletiva). Conclusão é necessária a produção de novos estudos que possam discutir as questões emocionais e sociais recebidas na anamnese que, eventualmente, estão relacionadas aos distúrbios do processamento auditivo e queixas de dificuldades escolares. .

Purpose the aim of this study was to attempt to correlate data from auditory processing with the data collected during the interview of children and teenagers. Method we analyzed the information from medical records of 51 patients of both genders, ages 5 to 20 years, assisted at the auditory processing evaluation service, UNIFESP. The features observed in the interview were: learning difficulties, presence of depression / motivation, use of medication, need for psychological treatment or pedagogical, and problems with attention and memory. Results we found 86% of cases with learning difficulties, 43% were receiving psychological treatment or pedagogical, 37% had problems with attention and memory, and 33% were using medication. None of these symptoms, however, could be associated with changes in temporal processing (ordinance and resolution) and recognition of non-verbal sounds in dichotic task (selective attention). Conclusion it is necessary to produce new studies to discuss the emotional and social issues received during the interview that possibly are related to auditory processing disorders and learning difficulties. .

Temporal Resolution Ability in Students with Dyslexia and Reading and Writing Disorders

Introduction: The Gaps-in-Noise (GIN) test assesses the hearing ability of temporal resolution. The development of this ability can be considered essential for learning how to read. Objective Identify temporal resolution in individuals diagnosed with reading and writing disorders compared with subjects with dyslexia. Methods: A sample of 26 subjects of both genders, age 10 to 15 years, included 11 diagnosed with dyslexia and 15 diagnosed with reading and writing disorders. Subjects did not display otologic, neurologic, and/or cognitive diseases. A control group of 30 normal-hearing subjects was formed to compare thresholds and percentages obtained from the GIN test. The responses were obtained considering two measures of analysis: the threshold gap and the percentage of correct gap. Results: The threshold was lower in the GIN for the typical group than for the other groups. There was no difference between groups with dyslexia and with reading and writing disorders. The GIN results of the typical group revealed a higher percentage of correct answer than in the other groups. No difference was obtained between the groups with dyslexia and with reading and writing disorders. Conclusion: The GIN test identified a difficulty in auditory ability of temporal resolution in individuals with reading and writing disorders and in individuals with dyslexia in a similar way...