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.

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

Abstract 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 ± 10.28 cells/100 μm2, 31-73, vs. 32 ± 7.47 cells/100 μm2, 25-48). The median area of stria vascularis was 55.0 ± 12.27 cells/100 μm2 (38-80) in the control, and 59.0 ± 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 ± 7.47 cells/100 μm2, 27-60) than in the control group (31 ± 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. Level of evidence: 3.

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.

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.

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.

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.

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.

Effects of Fish Oil Supplementation on Oxidative Stress Biomarkers and Liver Damage in Hypercholesterolemic Rats.

Metabolic syndrome, especially its component related to dyslipidemia, is related to the development of nonalcoholic fatty liver disease (NAFLD), which is a disease with a significant global prevalence. Supplementation with omega-3 polyunsaturated fatty acids emerged as a complementary therapeutic possibility for dyslipidemia, but its benefits are questioned. This paper aims at evaluating the effects of fish oil supplementation in rats with hypercholesterolemia induced by hypercholesterolemic diet (HD). The study design is based on an experimental model in which the animals were randomly divided into 3 groups: G1 (standard commercial feed + saline solution); G2 (hypercholesterolemic diet + saline solution) and G3 (hypercholesterolemic diet + fish oil) over a period of 16 weeks. Metabolic control parameters and oxidative stress biomarkers were evaluated according to standardized methodologies. The G3 group showed significantly lower values of plasma concentrations of TG, and hepatic myeloperoxidase as well as higher erythrocyte superoxide dismutase activity (p < 0.05). Regarding histopathological analysis, there was lipid accumulation in the liver of animals from group G2; meanwhile, hepatocytes reorganization and expressive reduction of lipid vacuoles and hepatic TG content was observed in group G3. This study demonstrated how fish oil supplementation reduced the plasma concentration and hepatic content of triglycerides, as well as liver tissue damage in histopathological analysis.

Olfactory Performance among Hospital Residents

Abstract 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 UPSITscore 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 β = 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.

Effects of ω-3 PUFA-Rich Oil Supplementation on Cardiovascular Morphology and Aortic Vascular Reactivity of Adult Male Rats Submitted to an Hypercholesterolemic Diet.

Atherosclerosis is a cardiovascular disease associated with abnormalities of vascular functions. The consumption of mono- and polyunsaturated fatty acids can be considered a strategy to reduce clinical events related to atherosclerosis. In the present study, we investigated the effects of supplementation with 310 mg of ω-3 PUFAs (2:1 eicosapentaenoic/docosahexaenoic acids) for 56 days on rats with hypercholesterolemia induced by a diet containing cholesterol (0.1%), cholic acid (0.5%), and egg yolk. Serum biochemical parameters were determined by the enzymatic colorimetric method. Assessment of vascular effects was performed by analysis of histological sections of the heart and aortic arch stained with hematoxylin and eosin and vascular reactivity of the aorta artery. We observed that treatment with ω-3 PUFAs did not promote alterations in lipid profile. On the other hand, we documented a favorable reduction in liver biomarkers, as well as contributions to the preservation of heart and aortic arch morphologies. Interestingly, the vascular reactivity of rat thoracic aortic preparations was improved after treatment with ω-3 PUFAs, with a decrease in hyperreactivity to phenylephrine and increased vasorelaxation promoted by acetylcholine. Our findings suggest that the supplementation of hypercholesterolemic rats with ω-3 PUFAs promoted improvement in liver and vascular endothelial function as well as preserving heart and aortic tissue, reinforcing the early health benefits of ω-3 PUFAs in the development of atherosclerotic plaque and further related events.

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.

Etiopathogenic features of severe epistaxis in histological samples from individuals with or without arterial hypertension.

There is a consensus that arterial hypertension (AH) is associated with stroke. Therefore, this study aimed to evaluate the histology of the microvasculature associated with the mucosa of the posterior nasal cavity to identify possible factors related to vascular weakening and rupture. Histological sections were obtained from hypertensive and normotensive individuals, regardless of epistaxis. Our results showed that the group with AH had: (a) smaller median diameter of the lumen of arteries and arterioles; (b) increased thickness of the intimal arteries and arterioles, slight inflammatory infiltrate, and rupture of internal elastic lamina; (c) greater thickness of the middle tunica in arterioles; (d) lower percentage of histological sections with non-injured intimal layers in capillaries, arterioles, and small arteries; (e) lower percentage of histological sections with intact media tunic and/or myocytes juxtaposed in arteries and arterioles; (f) no difference between the diameters of small arteries or arterioles. The intima was thicker in individuals with severe epistaxis than in the normotensive group, but it did not differ from the AH group. Thus, hypertension may cause structural lesions in the vascular layers, and in the absence of tissue repair and the persistence of AH, these lesions may favour vascular rupture, especially during hypertensive peaks.

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.

Morbidity in the postoperative follow-up of endoscopic anterior skull base surgery / Fatores relacionados à morbidade no seguimento pós-operatório da cirurgia endoscópica de base de crânio anterior

Abstract Introduction: Endoscopic access to the sellar region by videoendoscopy shows a low rate of surgical complications, with findings that indicate risk factors for reducing morbidities during and after the postoperative period. Objective: To evaluate, over a nine-year period, the acquisition of skills by the anterior skull base surgical team, according to the time of elimination of nasal crusts and/or the presence of morbidities in the postoperative follow-up of individuals treated in a tertiary public hospital. Methods: After confirming the diagnosis of skull base pathologies, the individuals in this study underwent endoscopic surgery according to the rostrocaudal or coronal axis. For the skull base reconstruction, the nasoseptal flap (associated or not with fascia lata with thigh fat) or free graft was used; clinical follow-up of individuals occurred for a minimum period of 12 months. To assess the impact of the surgical approach on patient clinical evolution, qualitative data related to smoking, post-nasal discharge, nasal flow, smell, taste, clinical symptoms of headache, cranial paresthesia, comorbidities and postoperative morbidities were obtained. Results: The most frequent diagnosis was pituitary macroadenoma (84.14%). The mean absence of crusts in this cohort was 124.45 days (confidence interval 95% = 119.50-129.39). There was a low cerebrospinal fluid fistula rate (3%). Reconstruction with the nasoseptal flap with a fat graft was an independent variable that recorded the highest mean time for the elimination of nasal crusts (=145 days, confidence interval 95% = 127.32-162.68). Allergic rhinitis and smoking were shown to be the most important and independent variables that increased the mean time to eliminate nasal crusts. Conclusion: The mean time to eliminate nasal crusts did not change over the years during which the procedures were performed, demonstrating the adequate training of the surgical team. Debridement and nasal irrigation with saline solutions should be performed more frequently and effectively in patients with allergic rhinitis, smokers and those who received the nasoseptal flap and fascia lata graft with autologous fat.

Resumo Introdução: O acesso endoscópico à região selar por videoendoscopia demonstra baixo índice de complicações cirúrgicas, com achados que apontam fatores risco para reduzir as morbidades durante e após o período pósoperatório. Objetivo: Avaliar fatores morbidades no seguimento pós-operatório de indivíduos atendidos em um hospital público terciário. Método: Depois de confirmado o diagnóstico de doenças da base do crânio, os indivíduos deste estudo foram submetidos a cirurgia endoscópica conforme o eixo rostrocaudal ou coronal. Para a reconstrução da base do crânio usava-se o retalho nasoseptal (associado ou não à fáscia lata com gordura de coxa) ou enxerto livre; o seguimento clínico dos indivíduos ocorreu por um período mínimo de 12 meses. Para avaliar o impacto da abordagem cirúrgica na evolução clínica dos pacientes foram obtidos os dados qualitativos relativos ao tabagismo, descarga pós-nasal, fluxo nasal, olfato, paladar, sintomas clínicos de dor de cabeça, parestesia craniana, comorbidades e morbidades pós-operatórias. Resultados: O diagnóstico mais frequente foi o macroadenoma hipofisário (84,14%). A média da ausência de crostas nesta coorte foi de 124,45 dias (intervalo de confiança [95% CI] 119,50-129,39). Baixo índice de fístula liquórica (3%). A reconstrução com o retalho nasoseptal com enxerto de gordura apresentou-se com variável independente que necessitou de maior tempo médio para a eliminação de crostas nasais (=145 dias, 95% CI 127,32-162,68). A rinite alérgica e o tabagismo se demonstraram como as variáveis mais importantes e independentes para aumentar o tempo médio de eliminação de crostas nasais. Conclusão: O tempo médio de eliminação de crostas nasais não se alterou ao longo dos anos em que os procedimentos foram feitos. Deve-se fazer com maior frequência e eficácia o debridamento e as irrigações nasais com soluções salinas nos pacientes com rinite alérgica, tabagistas e os que usaram o retalho nasoseptal e enxerto de fáscia lata com gordura autóloga.

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.

Morbidity in the postoperative follow-up of endoscopic anterior skull base surgery.

INTRODUCTION: Endoscopic access to the sellar region by videoendoscopy shows a low rate of surgical complications, with findings that indicate risk factors for reducing morbidities during and after the postoperative period. OBJECTIVE: To evaluate, over a nine-year period, the acquisition of skills by the anterior skull base surgical team, according to the time of elimination of nasal crusts and/or the presence of morbidities in the postoperative follow-up of individuals treated in a tertiary public hospital. METHODS: After confirming the diagnosis of skull base pathologies, the individuals in this study underwent endoscopic surgery according to the rostrocaudal or coronal axis. For the skull base reconstruction, the nasoseptal flap (associated or not with fascia lata with thigh fat) or free graft was used; clinical follow-up of individuals occurred for a minimum period of 12 months. To assess the impact of the surgical approach on patient clinical evolution, qualitative data related to smoking, post-nasal discharge, nasal flow, smell, taste, clinical symptoms of headache, cranial paresthesia, comorbidities and postoperative morbidities were obtained. RESULTS: The most frequent diagnosis was pituitary macroadenoma (84.14%). The mean absence of crusts in this cohort was 124.45 days (confidence interval 95%=119.50-129.39). There was a low cerebrospinal fluid fistula rate (3%). Reconstruction with the nasoseptal flap with a fat graft was an independent variable that recorded the highest mean time for the elimination of nasal crusts (=145 days, confidence interval 95%=127.32-162.68). Allergic rhinitis and smoking were shown to be the most important and independent variables that increased the mean time to eliminate nasal crusts. CONCLUSION: The mean time to eliminate nasal crusts did not change over the years during which the procedures were performed, demonstrating the adequate training of the surgical team. Debridement and nasal irrigation with saline solutions should be performed more frequently and effectively in patients with allergic rhinitis, smokers and those who received the nasoseptal flap and fascia lata graft with autologous fat.

Phagocytic activity of monocytes and neutrophils in patients with periodontitis, whether or not associated to type 2 diabetes.

Phagocytic functions by neutrophils/ monocytes and biochemical parameters were assessed in peripheral blood of patients with periodontitis, whether or not associated to type 2 diabetes, or patients with type 2 diabetes, or systemically healthy people. Fifty-eight participants were divided into four groups: Control - systemically and periodontally healthy patients (C, n=16), Periodontitis (P, n=14), Type 2 Diabetes (DM, n=11) and Periodontitis associated with type 2 diabetes (DMP, n=17). Blood samples were used to analyze phagocytic activity and the production of superoxide anion using optical microscopy. Significantly lower phagocytic activity of neutrophils was observed in non-opsonized samples (p = 0.008, Kruskal- Wallis) of the periodontitis group and in opsonized samples (p = 0.029, Kruskal-Wallis) of the periodontitis associated with type 2 diabetes group when these groups were compared to the healthy individuals when a 20:1 yeast: phagocyte stimulus was used. Periodontitis patients, whether associated (p = 0.0007, sensitized; Kruskal-Wallis, 20:1) or not with diabetes (p = 0.018 and 0.0007, in the proportions 5:1 and 20:1 yeast: monocyte respectively in sensitized samples; Kruskal-Wallis) also showed lower phagocytic function of monocytes compared to the control group. There was no significant difference in the production of superoxide anion among the evaluated groups. Severe clinical attachment loss was associated with lower levels of HDL in periodontitis patients and a higher percentage of A1C in diabetes with periodontitis patients (p<0.05; Pearson and Spearman correlations, respectively). Patients with both associated diseases had higher levels of triglycerides and CRP (p<0.001, Kruskal-Wallis) compared to patients with diabetes only. The results of the present study suggest that periodontitis negatively interferes with the innate immune response and may represent a major risk of systemic complications such as cardiovascular disease in diabetic patients or even in healthy individuals.

As funções fagocíticas de neutrófilos/monócitos e parâmetros bioquímicos foram avaliados no sangue periférico de pacientes com periodontite com ou sem diabetes do tipo 2, ou em pacientes com diabetes tipo 2, ou em pessoas saudáveis sistemicamente. 58 participantes foram divididos em quatro grupos: Controle - pacientes sistemicamente e periodontalmente saudáveis (C, n = 16), Periodontite (P, n = 14), Diabetes Tipo 2 (DM, n = 11) e Periodontite associada a diabetes tipo 2 (DMP, n = 17). Amostras de sangue foram usadas para analisar a atividade fagocítica e a produção de ânion superóxido por microscopia óptica. Observou-se menor atividade fagocítica dos neutrófilos em amostras não opsonizadas (p = 0,008, Kruskal-Wallis) do grupo periodontite e em amostras opsonizadas (p = 0,029, Kruskal-Wallis) do grupo periodontite associada ao diabetes tipo 2 quando esses grupos foram comparados aos indivíduos saudáveis sob um estímulo de levedura:monócito de 20:1. Pacientes com periodontite associada (p = 0,0007, sensibilizados; Kruskal-Wallis, 20: 1) ou não com diabetes (p = 0,018 e 0,0007, nas proporções 5: 1 e 20: 1 de levedura: monócito, respectivamente, em amostras sensibilizadas; Kruskal- Wallis) também demonstraram menor função fagocítica dos monócitos em comparação com o grupo controle. Não houve diferença significativa na produção de ânion superóxido entre os grupos avaliados. A perda de inserção clínica grave foi associada a níveis mais baixos de HDL na periodontite e maior percentual de A1C nos pacientes com periodontite associada ao diabetes (p<0,05; correlações de Person e Spearman, respectivamente). Os pacientes com ambas as doenças associadas apresentaram níveis mais altos de triglicerídeos e PCR (p<0,001, Kruskal- Wallis) em comparação aos pacientes com somente diabetes. Os resultados do presente estudo sugerem que a periodontite interfere negativamente na resposta imune inata e pode representar um risco maior para complicações sistêmicas, como a doença cardiovascular, em pacientes com diabetes ou mesmo em indivíduos saudáveis.

Quantification of lipid bodies in monocytes from patients with periodontitis.

OBJECTIVES: For the first time in the history of periodontics, the production of lipid bodies by monocytes was assessed from blood of patients with periodontitis in comparison to systemically healthy individuals. The purpose of this study was to compare the lipid body frequency within monocytes between healthy patients and those with periodontal disease. MATERIALS AND METHODS: A total of 30 participants (11 males and 19 females), were divided between orally healthy control subjects (C, n = 16) and periodontitis subjects (P, n = 14), in a cross-sectional study. Both groups were systemically healthy. The following clinical periodontal parameters were assessed: probing depth, clinical attachment level, visible plaque index and gingival bleeding on probing index. Blood samples were collected to obtain monocytes containing lipid bodies, which were analyzed by light microscopy. RESULTS: The periodontitis group demonstrated a higher corpuscular index than the control group (nonopsonized p = .0296 or opsonized p = .0459; Mann-Whitney). The frequency of monocyte cells containing lipid bodies (basal p = .0147, opsonized p = .0084 or nonopsonized, p = .026; Mann-Whitney) was also higher compared to those observed in healthy individuals. CONCLUSIONS: The data suggest that periodontitis may contribute to a higher production of lipid bodies. It was also hypothesized that a major production of lipid bodies by monocytes in severe periodontitis, compared to orally healthy subjects, could interfere with the innate immune response or represents a higher reservoir of cholesterol esters within macrophages and a major risk to systemic implications, such as atherosclerosis.

Phagocytic activity of monocytes and neutrophils in patients with periodontitis, whether or not associated to type 2 diabetes / Atividade fagocítica de monócitos e neutrófilos em pacientes com periodontite, associada ou não ao diabetes tipo 2

ABSTRACT Phagocytic functions by neutrophils/ monocytes and biochemical parameters were assessed in peripheral blood of patients with periodontitis, whether or not associated to type 2 diabetes, or patients with type 2 diabetes, or systemically healthy people. Fifty-eight participants were divided into four groups: Control - systemically and periodontally healthy patients (C, n=16), Periodontitis (P, n=14), Type 2 Diabetes (DM, n=11) and Periodontitis associated with type 2 diabetes (DMP, n=17). Blood samples were used to analyze phagocytic activity and the production of superoxide anion using optical microscopy. Significantly lower phagocytic activity of neutrophils was observed in non-opsonized samples (p = 0.008, Kruskal- Wallis) of the periodontitis group and in opsonized samples (p = 0.029, Kruskal-Wallis) of the periodontitis associated with type 2 diabetes group when these groups were compared to the healthy individuals when a 20:1 yeast: phagocyte stimulus was used. Periodontitis patients, whether associated (p = 0.0007, sensitized; Kruskal-Wallis, 20:1) or not with diabetes (p = 0.018 and 0.0007, in the proportions 5:1 and 20:1 yeast: monocyte respectively in sensitized samples; Kruskal-Wallis) also showed lower phagocytic function of monocytes compared to the control group. There was no significant difference in the production of superoxide anion among the evaluated groups. Severe clinical attachment loss was associated with lower levels of HDL in periodontitis patients and a higher percentage of A1C in diabetes with periodontitis patients (p<0.05; Pearson and Spearman correlations, respectively). Patients with both associated diseases had higher levels of triglycerides and CRP (p<0.001, Kruskal-Wallis) compared to patients with diabetes only. The results of the present study suggest that periodontitis negatively interferes with the innate immune response and may represent a major risk of systemic complications such as cardiovascular disease in diabetic patients or even in healthy individuals.

RESUMO As funções fagocíticas de neutrófilos/monócitos e parâmetros bioquímicos foram avaliados no sangue periférico de pacientes com periodontite com ou sem diabetes do tipo 2, ou em pacientes com diabetes tipo 2, ou em pessoas saudáveis sistemicamente. 58 participantes foram divididos em quatro grupos: Controle - pacientes sistemicamente e periodontalmente saudáveis (C, n = 16), Periodontite (P, n = 14), Diabetes Tipo 2 (DM, n = 11) e Periodontite associada a diabetes tipo 2 (DMP, n = 17). Amostras de sangue foram usadas para analisar a atividade fagocítica e a produção de ânion superóxido por microscopia óptica. Observou-se menor atividade fagocítica dos neutrófilos em amostras não opsonizadas (p = 0,008, Kruskal-Wallis) do grupo periodontite e em amostras opsonizadas (p = 0,029, Kruskal-Wallis) do grupo periodontite associada ao diabetes tipo 2 quando esses grupos foram comparados aos indivíduos saudáveis sob um estímulo de levedura:monócito de 20:1. Pacientes com periodontite associada (p = 0,0007, sensibilizados; Kruskal-Wallis, 20: 1) ou não com diabetes (p = 0,018 e 0,0007, nas proporções 5: 1 e 20: 1 de levedura: monócito, respectivamente, em amostras sensibilizadas; Kruskal- Wallis) também demonstraram menor função fagocítica dos monócitos em comparação com o grupo controle. Não houve diferença significativa na produção de ânion superóxido entre os grupos avaliados. A perda de inserção clínica grave foi associada a níveis mais baixos de HDL na periodontite e maior percentual de A1C nos pacientes com periodontite associada ao diabetes (p<0,05; correlações de Person e Spearman, respectivamente). Os pacientes com ambas as doenças associadas apresentaram níveis mais altos de triglicerídeos e PCR (p<0,001, Kruskal- Wallis) em comparação aos pacientes com somente diabetes. Os resultados do presente estudo sugerem que a periodontite interfere negativamente na resposta imune inata e pode representar um risco maior para complicações sistêmicas, como a doença cardiovascular, em pacientes com diabetes ou mesmo em indivíduos saudáveis.