Neuroprotective effects on microglia and insights into the structure-activity relationship of an antioxidant peptide isolated from Pelophylax perezi.

Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian's skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2 ) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 µg/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.

The peptide secreted at the water to land transition in a model amphibian has antioxidant effects.

In addition to the morphophysiological changes experienced by amphibians during metamorphosis, they must also deal with a different set of environmental constraints when they shift from the water to the land. We found that Pithecopus azureus secretes a single peptide ([M + H]+ = 658.38 Da) at the developmental stage that precedes the onset of terrestrial behaviour. De novo peptide and cDNA sequencing revealed that the peptide, named PaT-2, is expressed in tandem and is a member of the tryptophyllins family. In silico studies allowed us to identify the position of reactive sites and infer possible antioxidant mechanisms of the compounds. Cell-based assays confirmed the predicted antioxidant activity in mammalian microglia and neuroblast cells. The potential neuroprotective effect of PaT-2 was further corroborated in FRET-based live cell imaging assays, where the peptide prevented lipopolysaccharide-induced ROS production and glutamate release in human microglia. In summary, PaT-2 is the first peptide expressed during the ontogeny of P. azureus, right before the metamorphosing froglet leaves the aquatic environment to occupy terrestrial habitats. The antioxidant activity of PaT-2, predicted by in silico analyses and confirmed by cell-based assays, might be relevant for the protection of the skin of P. azureus adults against increased O2 levels and UV exposure on land compared with aquatic environments.

Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox).

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

P16 as a marker of carcinoma in effusions and peritoneal washing.

BACKGROUND: Considering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68. RESULTS: P16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%. CONCLUSION: Overexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.

Structure⁻Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells.

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure­function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5⁻10 µM), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 µM, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine.

Electrical stimulation structurally affects the tissues of the rectum and anus of nulliparous rats.

Considering that the muscles of the anus perform a critical role in maintaining continence, losses in their structure can negatively affect the physiological control of the intestinal contents. Anorectal electro-stimulation (ARES) has been reported to have a positive effect on the functionality of treated patients, but how ARES affects the structural tissues of the anorectal segment remains unknown. Because the study of how ARES structurally affects human tissues is not possible, this study aimed to clarify these effects in a murine model, which has a similar anorectal segment (structure and physiology) to humans. For the descriptive and comparative study, randomly selected nulliparous adult Wistar rats (n = 5) were submitted to 30 anorectal sessions of ARES with a biphasic current (700 µs, 50 Hz from 2 to 4 mA). After treatment, the animals were euthanized, and the anorectal segments were dissected and processed for histopathological analysis. Our results showed that ARES increased the widths of the mucosal, submucosal and muscle layers of the rectum, as well as the number of leukocytes in the mucosa. ARES also caused hyperplasia of the smooth muscle of the internal anal sphincter and hypertrophy of the external anal sphincter muscle. In conclusion, our results showed that ARES had not only a positive effect on the structure (morphology) of all tissues associated with the rectum and anus but, more importantly, on the structural gain of the muscles (hyperplasia and hypertrophy), which could point to a functional gain of the anal sphincter, reinforcing the applicability of ARES as a non-invasive treatment for anal incontinence.

Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium falciparum and on peritoneal cells of Swiss mice.

CONTEXT: Plants of the Piperaceae family produce piplartine that was used to synthesize the cinnamides. OBJECTIVE: To assess the effects of piplartine (1) and cinnamides (2-5) against the protozoa responsible for malaria and leishmaniasis, and peritoneal cells of Swiss mice. MATERIALS AND METHODS: Cultures of Leishmania amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells were incubated, in triplicate, with different concentrations of the compounds (0 to 256 µg/mL). The inhibitory concentration (IC50) in L. amazonensis and cytotoxic concentration (CC50) in peritoneal cell were assessed by the MTT method after 6 h of incubation, while the IC50 for P. falciparum-infected erythrocytes was determined by optical microscopy after 48 or 72 h of incubation; the Selectivity Index (SI) was calculated by CC50/IC50. RESULTS: All compounds inhibited the growth of microorganisms, being more effective against P. falciparum after 72 h of incubation, especially for the compounds 1 (IC50 = 3.2 µg/mL) and 5 (IC50 = 6.6 µg/mL), than to L. amazonensis (compound 1 = 179.0 µg/mL; compound 5 = 106.0 µg/mL). Despite all compounds reducing the viability of peritoneal cells, the SI were <10 to L. amazonensis, whereas in the cultures of P. falciparum the SI >10 for the piplartine (>37.4) and cinnamides 4 (>10.7) and 5 (= 38.4). DISCUSSION AND CONCLUSION: The potential of piplartine and cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical studies to evaluate their effects in murine malaria and to determine their mechanisms in cells of the immune system.

Ocellatin-PT antimicrobial peptides: High-resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems.

Although the mechanism of action of antimicrobial peptides (AMPs) is not clear, they can interact electrostatically with the cell membranes of microorganisms. New ocellatin-PT peptides were recently isolated from the skin secretion of Leptodactylus pustulatus. The secondary structure of these AMPs and their effect on Leishmania infantum cells, and on different lipid surface models was characterized in this work. The results showed that all ocellatin-PT peptides have an α-helix structure and five of them (PT3, PT4, PT6 to PT8) have leishmanicidal activity; PT1 and PT2 affected the cellular morphology of the parasites and showed greater affinity for leishmania and bacteria-mimicking lipid membranes than for those of mammals. The results show selectivity of ocellatin-PTs to the membranes of microorganisms and the applicability of biophysical methods to clarify the interaction of AMPs with cell membranes.

Collagen-based silver nanoparticles for biological applications: synthesis and characterization.

BACKGROUND: Type I collagen is an abundant natural polymer with several applications in medicine as matrix to regenerate tissues. Silver nanoparticles is an important nanotechnology material with many utilities in some areas such as medicine, biology and chemistry. The present study focused on the synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility. Three formulations of AgNPcol were physicochemical characterized, antibacterial activity in vitro and cell viability assays were analyzed. AgNPcol was characterized by means of the following: ultraviolet-visible spectroscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy, atomic absorption analysis, transmission electron microscopy and of X-ray diffraction analysis. RESULTS: All AgNPcol showed spherical and positive zeta potential. The AgNPcol at a molar ratio of 1:6 showed better characteristics, smaller hydrodynamic diameter (64.34 ± 16.05) and polydispersity index (0.40 ± 0.05), and higher absorbance and silver reduction efficiency (0.645 mM), when compared with the particles prepared in other mixing ratios. Furthermore, these particles showed antimicrobial activity against both Staphylococcus aureus and Escherichia coli and no toxicity to the cells at the examined concentrations. CONCLUSIONS: The resulted particles exhibited favorable characteristics, including the spherical shape, diameter between 64.34 nm and 81.76 nm, positive zeta potential, antibacterial activity, and non-toxicity to the tested cells (OSCC).

Nanopharmaceutical approach of epiisopiloturine alkaloid carried in liposome system: preparation and in vitro schistosomicidal activity.

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma. This disease control has been widely made by praziquantel-reference drug, but resistance to this drug has already been found. There has been the finding of an imidazole alkaloid in jaborandi leaves-epiisopiloturine, which has known activity against adult, young and egg forms of Schistosoma mansoni. This alkaloid is an apolar molecule with difficult solubility; therefore, the liposomal structure of epiisopiloturine was proposed. Liposomes are carrying structures of drugs that may enhance solubility of compounds such as epiisopiloturine. In this work, we report in vitro epiisopiloturine-loaded liposomes effect formed by different concentrations of lipids 9:1 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol and 8:2 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol. Results have showed that epiisopiloturine extraction and isolation have been successful through high-performance liquid chromatography-HPLC and its purity confirmed through mass spectrometry has showed 287 Da molecular mass. Formulations from 9:1 DPPC:cholesterol and 8:2 DPPC:cholesterol with loaded EPI (300 microg/ml) have killed parasites at 100% after incubation 96 h and 120 h, respectively. Confocal microscopy employed to observe morphological alterations in the tegument of adult form of Schistosoma mansoni. Details from interaction, between epiisopiloturine and liposome, have been achieved by semi-empirical AM1 calculations, which have showed that epiisopiloturine inside is more stable than the outside form, at least 10 kcal. This is first time that schistosomicidal activity has been reported for epiisopiloturine-loaded into liposome.

Pravastatin modulates macrophage functions of Leishmania (L.) amazonensis-infected BALB/c mice.

The control of leishmaniases poses an important challenge due to the scarcity and toxicity of the pharmacological options available. We have previously shown that pravastatin significantly improves the course of the disease in Leishmania (L.) amazonensis-infected BALB/c mice. Since the drug caused no direct effect on the parasite, we decided to evaluate its immunomodulatory action in this experimental model. To evaluate the impact of pravastatin treatment, BALB/c mice infected or not with L. (L.) amazonensis were treated with pravastatin (20 mg/kg daily) or saline during 30 or 90 days and phagocytosis, hydrogen peroxide, nitric oxide and the tumor necrosis factor production by peritoneal macrophages were assessed. We showed that pravastatin increased the phagocytosis mediated by complement and immunoglobulin receptors (63.5 to 130.3; p=0.03, t test), but not that occurring via pattern recognition receptors, induced a rise of nitric oxide production by macrophages (2.1 µM to 12.9 µM; p=0.04, Mann-Whitney test), endowing these cells to better kill ingested leishmania organisms, caused no modification of the otherwise increased production of hydrogen peroxide by macrophages, and reduced the overproduction of tumor necrosis factor (166.6 pg/mL to 3.9 pg/mL; p=0.016, Mann-Whitney test), a major component of the exacerbated inflammation associated to leishmaniases. Our findings point to the potential usefulness of pravastatin as an adjunct to the treatment of leishmaniases, based on its powerful immunomodulatory effects and low toxicity.

Development and antibacterial activity of cashew gum-based silver nanoparticles.

The present study describes the development of a green synthesis of silver nanoparticles reduced and stabilized by exuded gum from Anacardium occidentale L. and evaluates in vitro their antibacterial and cytotoxic activities. Characterization of cashew gum-based silver nanoparticles (AgNPs) was carried out based on UV-Vis spectroscopy, transmission electron microscopy and dynamic light scattering analysis which revealed that the synthesized silver nanoparticles were spherical in shape, measuring about 4 nm in size with a uniform dispersal. AgNPs presented antibacterial activity, especially against Gram-negative bacteria, in concentrations where no significant cytotoxicity was observed.

The skin secretion of the amphibian Phyllomedusa nordestina: a source of antimicrobial and antiprotozoal peptides.

Antimicrobial peptides (AMPs) from the dermaseptin and phylloseptin families were isolated from the skin secretion of Phyllomedusa nordestina, a recently described amphibian species from Northeastern Brazil. One dermaseptin and three phylloseptins were chosen for solid phase peptide synthesis. The antiprotozoal and antimicrobial activities of the synthetic peptides were determined, as well as their cytotoxicity in mouse peritoneal cells. AMPs are being considered as frameworks for the development of novel drugs inspired by their mechanism of action.

Morphometry of latent palmprints as a function of time.

In many crimes, the elapsed time between production and collecting fingermark traces is crucial. and a method able to detect the aging of latent prints would represent an improvement in forensic procedures. Considering that as the latent print gets older, substantial changes in the relative proportion of individual components secreted by skin glands could affect the morphology of ridges, morphometry could be a potential tool to assess the aging of latent fingermarks. Then, considering the very limited research in the field, the present work aims to evaluate the morphometry of latent palmprint ridges, as a function of time, in order to identify an aging pattern. The latent marks were deposited by 20 donors on glass microscope slides considering pressure and contact angle, and then were maintained under controlled environmental conditions. The morphometric study was conducted on marks developed with magnetic powder in 7 different time intervals after deposition (0, 5, 10, 15, 20, 25 or 30 days); 60 ridges were evaluated for each developed mark. The results showed that: 1) the method for the replacement and mixing of skin secretions on the palm was appropriate to ensure reproducibility of latent prints, and 2) considering the studied group, there was a time-dependent reduction in the width of ridges and on the percentage of visible ridges over 30 days. Results suggest the possibility of using the morphometric method to determine an aging profile of latent palmprints on glass surface, aiming for forensic purposes.

ACW-02 an Acridine Triazolidine Derivative Presents Antileishmanial Activity Mediated by DNA Interaction and Immunomodulation.

The present study proposed the synthesis of a novel acridine derivative not yet described in the literature, chemical characterization by NMR, MS, and IR, followed by investigations of its antileishmanial potential. In vitro assays were performed to assess its antileishmanial activity against L. amazonensis strains and cytotoxicity against macrophages through MTT assay and annexin V-FITC/PI, and the ability to perform an immunomodulatory action using CBA. To investigate possible molecular targets, its interaction with DNA in vitro and in silico targets were evaluated. As results, the compound showed good antileishmanial activity, with IC50 of 6.57 (amastigotes) and 94.97 (promastigotes) µg mL-1, associated with non-cytotoxicity to macrophages (CC50 > 256.00 µg mL-1). When assessed by flow cytometry, 99.8% of macrophages remained viable. The compound induced an antileishmanial effect in infected macrophages and altered TNF-α, IL-10 and IL-6 expression, suggesting a slight immunomodulatory activity. DNA assay showed an interaction with the minor grooves due to the hyperchromic effect of 47.53% and Kb 1.17 × 106 M-1, and was sustained by docking studies. Molecular dynamics simulations and MM-PBSA calculations propose cysteine protease B as a possible target. Therefore, this study demonstrates that the new compound is a promising molecule and contributes as a model for future works.

Olfactory Performance among Hospital Residents.

Introduction Smell plays an important role in the maintenance of health and quality of life of the general population. Health workers with olfactory impairment may not be able to help diagnose certain diseases, and subsequently increase the risk of hazardous events and mortality among those affected. 'Odor learning' requires repeated experiences with different smells to develop a discriminatory ability, and this is a process that takes years. Because of that, physicians of certain medical specialities have better odor detection than others. Objective To study the olfactory performance and associated factors of otorhinolaryngology residents compared with residents of different medical specialities in a representative sample of a tertiary hospital. Methods The University of Pennsylvania Smell Identification Test (UPSIT) was used to compare olfactory performance. Clinical and epidemiological data were collected among 42 hospital residents. Results Otorhinolaryngology residents presented an average UPSIT score of 35.0, and the other residents, a score of 32.8 ( p = 0.02) Of all the residents, 40.5% showed some grade of olfactory impairment. Half of the females students in the first year of residency showed olfactory dysfunction. The multivariate analyses found age ( p = 0.03; 95% confidence interval for ß = 0.33) to be an independent predictor of the UPSIT score. Conclusion The present study demonstrated that otorhinolaryngology residents have greater olfactory capacity compared with other residents. Future studies should explore the relevant factors of olfactory impairment and its impact on quality of life in this population.

Methodological Approaches for Vocal Folds Experiments in Laryngology: A Scoping Review.

OBJECTIVE: The aim of this study was to describe the methodological approaches adopted in experimental researches in laryngology intervention studies. METHODS: The study was performed as a scoping review using the electronic databases Medline (PubMed), Web of Science, Embase, BioMed Central and SCOPUS. These databases were manually searched from 1995 (or its inception) until the most recently published articles in June 2022. The inclusion criteria were as follows: a) studies performed with animal models in voice and/or larynx therapy, intervention and/or surgery; b) studies with participant populations composed with animals; c) studies containing original research; d) studies performed with at least one objective measurement for treatment and or intervention; e) studies reporting at least one method of larynx intervention; and f) publications written in English, Spanish or Portuguese. The exclusion criteria were as follows: a) studies considering without any objective intervention and or treatment; b) studies without animal models; and c) studies that reviewed articles or books. These criteria were set to increase inter-study comparability. RESULTS: There were found 26 studies that showed that in experimental laryngology. There were retrieved four main characteristics in the retrieved studies. It was observed five major groups of experimental models used for assessing vocal folds: dog (38.5%), rat/mouse (23,1%), pig (23.1%), rabbit (19.2%), human (11.5%), and sheep (3.8%). In addition, three characteristics were observed: sample (up to 20 subjects 88.5%), type of surgery/intervention (100%) and duration (up to 30 days 61.5%). CONCLUSION: In experimental laryngology, the state of the art is grounded on mainly in dog, rat and pig in vocal folds assessment. Up to 20 subjects, surgery/intervention and experimental trial lasting no more than 30 days are frequent methodological approaches in this research field.

Alterations in innate immune responses of patients with chronic rhinosinusitis related to cystic fibrosis.

The role of phagocytes of children with cystic fibrosis (CF) associated with different phenotypes of chronic rhinosinusitis (CRS) is unclear. The aim of this study was to evaluate the phagocytic capacity of blood neutrophils and monocytes and production of superoxide anion by phagocytes in patients with CF with or without chronic rhinosinusitis and with or without nasal polyps (NP). This cross-sectional study was established in 2015-2017 in a tertiary reference center to the CF treatment, Brasilia, Brazil. Sample included 30 children volunteers with CRS related to CF (n = 16) and control subjects (n = 14). Epidemiological and clinical data were compared. Collection of 15 mL of peripheral blood and nasal endoscopy to identify the presence or absence of nasal polyps (NP) were performed. Phagocytosis of Saccharomyces cerevisiae by pathogen-associated molecular pattern receptors and opsonin receptors was assessed. Superoxide anion production was evaluated. The control group showed a higher phagocytic index to monocytes and neutrophils than to the CF or CF+CRS with NP groups [Kruskal-Wallis p = 0.0025] when phagocytosis were evaluated by pathogen-associated molecular pattern receptors (5 yeasts/cell). The phagocytic index of the CF+CRS without NP group was higher than in the CF+CRS with NP group (Kruskal-Wallis p = 0.0168). In the control group, the percentage of phagocytes involved in phagocytosis and superoxide anion production (74.0 ± 9.6%) were higher in all CF groups (p < 0,0001). The innate immune response, represented by phagocytic activity and superoxide anion production by monocytes and neutrophils was more impaired in patients with CF related or not related to CRS than in the control group. However, the phagocytic function of patients without NP showed less impairment.

Melatonin prevents age-related hearing loss in the murin experimental model.

OBJECTIVE: The present study aimed to perform a morphological and morphometric analysis of cochlear structures of C57BL/6J mice receiving oral melatonin for a 12-month period. METHODS: 32 male C57BL/6J were divided into control and melatonin groups. Control received saline and ethanol solution and melatonin group, 50 µL of 10 mg of melatonin/kg/day orally for a 12-month period. After de experiment the animals were sacrificed into a 40% concentration of CO2 chamber, and the blades were morphological and morphometrically analyzed. RESULTS: The melatonin group revealed a higher median density of viable cells (45 ±â€¯10.28 cells/100 µm2, 31-73, vs. 32 ±â€¯7.47 cells/100 µm2, 25-48). The median area of stria vascularis was 55.0 ±â€¯12.27 cells/100 µm2 (38-80) in the control, and 59.0 ±â€¯16.13 cells/100 µm2 (40-134) in the melatonin group. The morphometric analysis of the spiral ligament reveals a higher median of total viable neurons in the melatonin (41 ±â€¯7.47 cells/100 µm2, 27-60) than in the control group (31 ±â€¯5.68 cells/100 µm2, 21-44). CONCLUSION: Although melatonin is a potent antioxidant, it does not completely neutralize the occurrence of presbycusis; however, it may delay the onset of this condition.

Perspectives on the Therapeutic Effects of Pelvic Floor Electrical Stimulation: A Systematic Review.

Pelvic, perineal, and nervous lesions, which derive principally from pregnancy and childbirth, may lead to pelvic floor dysfunctions, such as organ prolapses and lesions in the nerves and muscles due to muscle expansion and physiology. It is estimated that 70% of women affected by this clinical picture have symptoms that do not respond to the classical treatments with antimuscarinic and anticholinergic drugs. Therefore, resorting to efficient alternatives and less invasive methods is necessary to assist this public health problem that predominantly affects the female population, which is more susceptible to the risk factors. This study aimed to perform an updated and comprehensive literature review focused on the effects of pelvic floor electrical stimulation, considering new perspectives such as a correlation between electric current and site of intervention and other molecular aspects, different from the present reviews that predominantly evaluate urodynamic aspects. For that purpose, PubMed and ScienceDirect databases were used to perform the search, and the Methodi ordinatio method was applied. With well-researched therapeutic effects, electrical stimulation induced promising results in histological, nervous, and molecular evaluations and spinal processes, which showed beneficial results and revealed new perspectives on ways to evoke responses in the lower urinary tract in a non-invasive way. Thus, it is possible to conclude that this type of intervention may be a non-invasive alternative to treat pelvic and perineal dysfunctions.