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1.
Org Biomol Chem ; 22(29): 5987-5998, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38989906

RESUMO

Herein we report a study on the sequential substitution of different nucleophiles on cyanuric chloride to obtain potential candidates for metal sensors (5a-c). The set of nucleophiles on the 1,3,5-triazine ring includes a phenolic BODIPY, an aminoalkyl pyridine and aminoalkyl phosphoramidates, each one designed to play a specific role in the final fluoroionophore. Three new triazine triads were synthesized in similar yields: 5a (45%), 5b (43%) and 5c (52%) after a methodical sequential combination of the nucleophiles via thermodependent nucleophilic aromatic substitution of the three chlorine atoms of cyanuric chloride. To ratify the synthetic results we simulated the reaction mechanisms for the different nucleophiles, aiming to address the distinctive orthogonality and temperature control inherent in this process, identifying and providing a sound rationale for any preferential sequence of nucleophiles inserted into the triazine core. According to our experimental and computational analysis (thermo- and kinetic preferences), we have identified the following preferential order for the sequential substitution: p-hydroxybenzaldehyde > 2-(pyridin-2-yl)ethanamine > aminoalkyl phosphoramidate, indicating that all steps follow a single-step process (concerted) in two stages, where nucleophilic addition precedes leaving group dissociation. The Meisenheimer σ-complex was identified as a transition state structure, with insufficient stability to exist as an intermediate. We observed a consistent and progressive increase in barrier height: 2-8 kcal mol-1 for the first step, 9-15 kcal mol-1 for the second step, and >15 kcal mol-1 for the third substitution. These findings align with the experimental observation of thermodependency in the sequential substitution.

2.
J Nat Prod ; 87(3): 456-469, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38395785

RESUMO

The phytochemical investigation of the leaves and trunk bark of a specimen of Ocotea aciphylla collected in the southern portion of the Amazon forest led to the isolation of an oxabicyclo[3.2.2]nonane-type neolignan and 15 bicyclo[3.2.1]octanoid neolignans, 14 of which are unreported compounds (2-15), including one with an unusual oxidation pattern of the side chain at C-1' and two rare 7.1',8.3'-connected bicyclo[3.2.1]octanoid derivatives. Their structures and relative configurations were determined by extensive spectrometric analysis based on 1D- and 2D-NMR spectroscopy and HRESIMS data, while their absolute configurations were unambiguously assigned using electronic and vibrational circular dichroism data assisted by density functional theory calculations. Additionally, known sesquiterpenes, phenylpropanoids, and phytosterols were also isolated.


Assuntos
Lignanas , Ocotea , Lignanas/química , Ocotea/química , Alcanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Dicroísmo Circular
3.
J Hum Hypertens ; 38(5): 404-412, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38291242

RESUMO

Family history of hypertension is associated with early autonomic dysfunction and increased oxidative stress. These alterations have been found to be reinforced by the overweight factor. Conversely, an active lifestyle is effective in improving the mechanisms regulating blood pressure control. Hence, we ought to investigate the effects of an active lifestyle on the hemodynamic, autonomic and oxidative stress parameters in individuals carrying both family history of hypertension and overweight risk factors. Fifty-six normotensive males were divided into four groups: eutrophic offspring of normotensive parents (EN, n = 12), eutrophic and inactive with hypertensive parents (EH, n = 14), overweight and inactive with hypertensive parents (OH, n = 13), and overweight and physically active with hypertensive parents (OAH, n = 17). Cardiovascular autonomic modulation was assessed by heart rate (HRV) and blood pressure (BPV) variability indexes. Oxidative stress included pro/antioxidant markers and nitrite concentration. Inactive offspring of hypertensive parents (EH and OH) showed higher LFSBP (vs EN), an indicator of sympathetic outflow to the vasculature and reduced anti-oxidant activity (vs EN), while higher pro-oxidant markers were found exclusively in OH (vs EN and EH). Conversely, the OAH group showed bradycardia, higher vagally-mediated HFabs index (vs OH and EN), lower sympathovagal balance (vs OH) and preserved LFSBP. Yet, the OAH showed preserved pro/antioxidant markers and nitrite levels. Our findings indicates that overweight offspring of hypertensive parents with an active lifestyle have improved hemodynamic, cardiac autonomic modulation and oxidative stress parameters compared to their inactive peers.


Assuntos
Sistema Nervoso Autônomo , Pressão Sanguínea , Frequência Cardíaca , Hipertensão , Sobrepeso , Estresse Oxidativo , Humanos , Masculino , Hipertensão/fisiopatologia , Hipertensão/genética , Sistema Nervoso Autônomo/fisiopatologia , Adulto , Sobrepeso/fisiopatologia , Sobrepeso/complicações , Exercício Físico , Pessoa de Meia-Idade , Fatores de Risco
4.
Sci Rep ; 13(1): 10148, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349360

RESUMO

Preserving vascular function is crucial for preventing multiorgan failure and death in ischemic and low-pressure states such as trauma/hemorrhagic shock (T/HS). It has recently been reported that inhibiting circulating proteases released from the bowel to the circulation during T/HS may preserve vascular function and improve outcomes following T/HS. This study aimed to evaluate the role of the serine protease inhibitor gabexate mesilate (GM) in preserving vascular function during T/HS when given enterally. We studied the vascular reactivity of mesenteric arteries from male Wistar rats treated with enteral GM (10 mg/kg) (GM-treated, n = 6) or control (Shock-control, n = 6) following (T/HS) using pressure myography. Concentration-response curves of endothelial-dependent and endothelial-independent agonists (e.g., acetylcholine, sodium nitroprusside) ranging from 10-10 to 10-5 M were performed. In a second set of experiments, ex-vivo arteries from healthy rats were perfused with plasma from shocked animals from both groups and vascular performance was similarly measured. Arteries from the GM-treated group demonstrated a preserved concentration-response curve to the α1 adrenergic agonist phenylephrine compared to arteries from Shock-control animals (- logEC50: - 5.73 ± 0.25 vs. - 6.48 ± 0.2, Shock-control vs. GM-treated, p = 0.04). When perfused with plasma from GM-treated rats, healthy arteries exhibited an even greater constriction and sensitivity to phenylephrine (- logEC50: - 6.62 ± 0.21 vs. - 7.13 ± 0.21, Shock-control vs. GM-treated, p = 0.02). Enteral GM also preserved the endothelium-dependent vascular response to agonists following T/HS and limited syndecan-1 shedding as a marker of glycocalyx compromise (41.84 ± 9 vs. 17.63 ± 3.97 ng/mL, Shock-control vs. GM-treated, p = 0.02). Syndecan-1 cleavage was correlated with plasma trypsin-like activity (r2 = 0.9611). Enteral gabexate mesilate was able to maintain vascular function in experimental T/HS, which was reflected by improved hemodynamics (mean arterial pressure 50.39 ± 7.91 vs. 64.95 ± 3.43 mmHg, Shock-control vs. GM treated, p = 0.0001). Enteral serine protease inhibition may be a potential therapeutic intervention in the treatment of T/HS.


Assuntos
Choque Hemorrágico , Gabexato/farmacologia , Gabexato/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/enzimologia , Endotélio/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , Inibidores de Serina Proteinase/uso terapêutico , Ratos Wistar , Masculino , Animais , Ratos
5.
Braz J Microbiol ; 54(2): 1275-1285, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37074557

RESUMO

Glanders is a contagious disease of equids caused by the Gram-negative bacterium Burkholderia mallei. In Brazil, the disease is considered to be reemerging and has been expanding, with records of equids with positive serology in most of the federative units. However, there are few reports describing the genotypic detection of the agent. This study demonstrated the detection of B. mallei by species-specific PCR directly from tissues or from bacterial cultures, followed by amplicon sequencing in equids (equines, mules, and asinines) with positive serology for glanders in all five geographic regions of Brazil. The molecular evidence of B. mallei infection in serologically positive equids in this study expands the possibility of strain isolation and the conduction of epidemiological characterizations based on molecular information. The microbiological detection of B. mallei in cultures from nasal and palate swabs, even in equids without clinical manifestations, raises the possibility of environmental elimination of the agent.


Assuntos
Burkholderia mallei , Mormo , Animais , Cavalos , Burkholderia mallei/genética , Mormo/diagnóstico , Mormo/epidemiologia , Mormo/microbiologia , Brasil/epidemiologia , Reação em Cadeia da Polimerase , Técnicas de Amplificação de Ácido Nucleico
6.
Rev Alerg Mex ; 69(3): 138-141, 2023 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-36869013

RESUMO

INTRODUCTION: Hereditary angioedema is an autosomal dominant genetic disease, associated with increased levels of bradykinin. It is classified into 3 types according to the C1-INH enzyme. The diagnosis is clinical and laboratory. Its treatment is divided into short- and long-term and crisis prophylaxis. CASE REPORT: 40-year-old female patient who came to the emergency service for labial edema without resolution with corticosteroids. The tests for IgE, C4 and C1 esterase inhibitors had a low result. She currently uses danazol prophylactically and fresh frozen plasma in crises. CONCLUSIONS: Since it is a disease that considerably affects the quality of life, hereditary angioedema must be diagnosed and an effective treatment plan made to prevent or reduce its complications.


INTRODUCCIÓN: El angioedema hereditario es una enfermedad genética autosómica dominante, asociada con aumento de las concentraciones de bradicinina. Se clasifica en tres tipos, de acuerdo con la enzima C1-INH. El diagnóstico se establece por las manifestaciones clínicas y los estudios de laboratorio. El tratamiento consiste profilaxis a corto y largo plazo, y protocolo para el control de las crisis. REPORTE DEL CASO: Paciente femenina de 40 años, que acudió al servicio de Urgencias por edema labial, sin reacción al tratamiento con corticosteroides. Se detectaron concentraciones bajas de IgE, C4 e inhibidores de la esterasa C1. Se estableció el diagnóstico de angioedema hereditario. Actualmente se mantiene en tratamiento profiláctico con danazol y plasma fresco congelado para el control de las crisis. CONCLUSIONES: El angioedema hereditario es una enfermedad que afecta considerablemente la calidad de vida; por tanto, debe diagnosticarse de forma oportuna y establecer un plan de tratamiento eficaz, con la intención de prevenir o reducir las complicaciones.


Assuntos
Angioedemas Hereditários , Feminino , Humanos , Adulto , Bradicinina , Qualidade de Vida , Danazol
7.
Pathogens ; 12(1)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36678496

RESUMO

The aim of this study was to determine the incidence of infections and cytological abnormalities and to investigate possible predisposing factors such as sociodemographic characteristics, sexual behavioral habits, and gynecological and obstetric backgrounds. Between 2013 and December 2016, a cross-sectional study was conducted among 429 consenting women, from whom cervical samples were tested for the presence of Human papillomavirus (HPV) by polymerase chain reaction (PCR). Susceptibility to HPV infection was assessed by binary logistic regression in light of possible predisposing factors, which were collected using a questionnaire. In our sample population, the prevalence of HPV infection was 49%; high-risk types had a higher prevalence of 89.1%. A larger proportion of HPV-infected women were under 25 years of age, were single, and had monthly incomes up to minimum wage. Multivariate binary logistic regression analysis showed that age younger than 25 years increased the odds of infection fivefold, while a monthly income of one to three minimum wages provided protection against HPV infection, even if the women were married or had a cohabiting partner. In the HPV-positive group, squamous intraepithelial lesions (SIL) occurred more frequently in women who earned up to one minimum wage monthly, but a monthly income of one to three minimum wages protected against the development of SIL. The results suggest that age, marital status, and monthly income are important cofactors for HPV infection and the development of SIL.

8.
Ther Adv Infect Dis ; 10: 20499361221148007, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654871

RESUMO

Background: Understanding the correlation between the methods of monitoring surface cleaning and disinfection (SCD) is fundamental for better infection control. Purpose: This study aims to correlate the SCD monitoring methods in a Brazilian pediatric unit. This is an exploratory, longitudinal, and correlational study. Methods: The study was conducted in a pediatric hospitalization unit of a medium-sized hospital from December 2020 to March 2021. Four high-contact surfaces were analyzed before and after the cleaning and disinfection process by means of visual inspection, quantification of adenosine triphosphate (ATP), and colony-forming unit (CFU) count. The study consisted of three stages: stage I involving situational diagnosis of the SCD process; stage II referring to the implementation of the Surface Cleaning and Disinfection Standardization Program (SCDSP); and stage III involving long-term assessment after implementing the program. A total of 192 assessments were performed in each stage, totaling 576 in the three study stages. Conclusions: A significant correlation was found between the ATP quantification methods and microbial count in the bed railing (p = 0.009) and companion's armchair (p = 0.018) surfaces. In both cases, Spearman's correlation coefficients were positive, indicating a positive correlation between ATP and microbial count scores, that is, the higher the ATP values (in RLUs), the greater the microbial counts (in CFUs/cm2). The analysis of the ROC curves suggests that the surfaces presenting ATP below 108 RLUs can be considered approved. The ATP method yielded 78.6% sensitivity; in turn, microbial count presented a sensitivity of 85.7%. It is important to use different methods to monitor the cleaning and disinfection of surfaces, as each one has different sensitivity and specificity.

9.
Environ Manage ; 71(2): 483-493, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36459196

RESUMO

The application of the mitigation hierarchy (MH) to mining projects is challenging in situations of locational overlap between endemic flora and mineral deposits. We review flora surveys conducted in connection with the environmental impact assessment of several iron ore mining projects in an area of high degree of endemism in Eastern Amazon to discuss the practical implications of anticipating conservation strategies. Desktop studies and secondary data review were conducted to guide field searches to determine the distribution of endemic flora, resulting in 45 out of 46 endemic plant species having their known distribution extended to new areas. A framework for positioning flora conservation strategies in the MH is presented. Specific habitat requirements and scarce knowledge about endangered and endemic flora species are a conservation obstacle, since essential information to define species conservation strategies may be lacking. We show that anticipating conservation strategies can minimize time-lag uncertainties related to restoration success and biodiversity offsets. The more effort is placed in the preventative steps of the MH, the smaller the time-lag between impact (biodiversity losses) and conservation outcomes (biodiversity gains), decreasing uncertainties and reducing risks to biodiversity.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Conservação dos Recursos Naturais/métodos , Biodiversidade , Mineração
10.
J Mol Model ; 28(11): 369, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36305977

RESUMO

4-Quinolones compose a remarkable class of compounds that show various pharmacological applications. In particular, the activities of both (S) and (R) enantiomers of 2-aryl-2,3-dihydro-4(1H)-quinolones have made them an object of befitting interest for asymmetric synthesis. Although readily yielded as a racemic mixture from an one-pot reaction between 2-aminoacetophenone and benzaldehyde, a pathway for the metal-free enantioselective one-pot synthesis of the (S) isomer is not completely clear. In the present work, guided by the burgeoning role of organocatalysis in asymmetric synthesis and recent experimental insight into the most likely reaction mechanism, we report the in silico screening for a roster of MacMillan chiral imidazolidinones through quantum mechanics calculations. Two stereopredictive models yielding similarly high expected ee (up to 97%) were proposed. The role of aromatic interactions for the control of enantioselectivity was systemically studied, as well as the Pro-S si-enantiofacial attack activation energies, which were found to correlate well (R2 = 0.75) with the reported Bürgi-Dunitz angle for the expected intramolecular Mannich reaction mechanism.


Assuntos
Quinolonas , Catálise , Estereoisomerismo
11.
J Nat Prod ; 85(9): 2184-2191, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-35998343

RESUMO

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-ß-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1ß. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 µM, respectively. The maximum inhibition of IL-1ß production was 23.5% (1), 27.3% (2), and 32.5% (3).


Assuntos
Anti-Inflamatórios , Justicia , Lignanas , Alantoína/química , Alantoína/isolamento & purificação , Alantoína/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Furanos/química , Furanos/isolamento & purificação , Furanos/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/química
12.
Cytokine ; 158: 156007, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35985174

RESUMO

The purpose of this review was to examine current evidence on immunomodulation mediated by conventional drugs and the use of novel biological agents for the treatment of rheumatoid arthritis (RA). Currently, treatment is focused on maximizing quality of life through sustained clinical remission and/or attenuating disease activity. To do so, disease-modifying antirheumatic drugs, especially methotrexate, are used alone or in combination with other drugs, including leflunomide, biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). The most recent strategies modulate the immune response of the individual RA patient using tsDMARDs such as JAK inhibitors and bDMARDs such as ig-CTLA-4, anti- IL6R, anti-TNF-α and anti-CD20. To better understand current immunopharmacological interventions, we also looked at documented mechanisms of RA-mediated immunomodulation, highlighting perspectives potentially boosting RA treatment.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Quimioterapia Combinada , Humanos , Qualidade de Vida , Inibidores do Fator de Necrose Tumoral
13.
Photodiagnosis Photodyn Ther ; 39: 103016, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35840009

RESUMO

Methylene blue (MB) mediated photodynamic therapy (PDT) is an emerging treatment for different kinds of skin lesions and ulcers. Our case report aims to assess its potential in treating diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Patients presented with complex chronic wounds larger than 40 cm2 with low healing potential. Once a week, patients had an aqueous formulation of MB at a concentration of 10 mg/mL (1% w/v) applied topically on their wounds, which were then irradiated with a light-emitting diode (LED) light source (660 nm, 3.8 J/cm2) with 9 mW/cm2 on tissue surface. Symptom improvement and recurrence rates were assessed with a long-term follow-up from 2018 to 2021. The results were satisfactory, with significant wound size reduction, and a decrease in aspects indicative of infection including odor, presence of exudates, and purulence. After methylene blue-mediated photodynamic therapy (MB-PDT), patients showed significantly reduced wound secretion, no signs of local reaction, and no adverse effects such as burning sensation, pain, itching, skin erythema, or general malaise.


Assuntos
Pé Diabético , Fotoquimioterapia , Pé Diabético/tratamento farmacológico , Humanos , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Cicatrização
14.
Magn Reson Chem ; 60(6): 533-540, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35229358

RESUMO

The combination of computational methods and experimental data from Nuclear Magnetic Resonance (NMR) is a considerably valuable tool in the elucidation of new natural product structures and, also, in the structural revision of previously reported compounds. Until recently, only classical statistical parameters were used, for example, linear correlation coefficient (R2 ), mean absolute error (MAE), or root mean square deviation (RMSD), as a way to statistically "validate" the structure pointed out by experimental NMR spectra. Regarding the resolution of the relative configuration of organic molecules, novel tools were available in the last few years to assist in the NMR elucidation process. The most relevant are DP4+, which is based on a Bayesian probability, and ANN-PRA, which is based on artificial neural networks. The combined application of these tools has become the most accurate and important alternative to solve structural and stereochemical problems in natural product chemistry. Therefore, herein, in this case study, we intended to promote these novel tools, exploring the strengths and limitations of each approach in resolving the relative configuration of the sesquiterpene alpha-bisabol. We also highlighted the advantages of the complementary use of H- and C-DP4+ to obtain optimal results in the differentiation of the stereoisomers, validating the proposal with ANN-PRA method.


Assuntos
Produtos Biológicos , Teorema de Bayes , Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , Estereoisomerismo
15.
Am J Case Rep ; 23: e934401, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35304434

RESUMO

BACKGROUND Abdominal pregnancy is a special type of ectopic pregnancy, characterized by implantation of the embryo in the peritoneal cavity, with tubal, ovarian, and intraligamentary pregnancies excluded, accounting for approximately 1% of all cases. It was first reported in 1708 after an autopsy and since then numerous cases have been reported, with a current incidence of 1: 10 000 to 1: 30 000 pregnancies. CASE REPORT We report the case of a 27-year-old woman, resident of the city of Caxias do Sul, Brazil, with an extra-uterine pregnancy by ultrasound diagnosis at 25 weeks and 1 day of gestational age and a live fetus. CONCLUSIONS Abdominal gestation is a rare type of ectopic pregnancy and is characterized as a life-threatening situation. Its biggest challenge is to make an early diagnosis, since most cases go unnoticed at the ultrasound performed in the first trimester, and when symptomatic, they do not present themselves in a specific way. When necessary, MRI has been shown to greatly elucidate such cases. Moreover, the therapeutic decision also presents some disparities in the literature. Although it is known that open surgery is best option, there are still many doubts regarding whether to perform placental extraction since its removal process can cause abundant bleeding, putting the patient at risk during the surgical procedure, in the same way that its maintenance and the use of drug treatment can also aggravate the patient's clinical picture.


Assuntos
Gravidez Abdominal , Adulto , Brasil , Diagnóstico Tardio , Feminino , Idade Gestacional , Humanos , Nascido Vivo , Placenta , Gravidez , Gravidez Abdominal/diagnóstico por imagem , Gravidez Abdominal/cirurgia , Salpingectomia
16.
J Cancer Res Clin Oncol ; 148(4): 793-802, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35083551

RESUMO

PURPOSE: Every year, more than half a million women are diagnosed with cervical cancer (CC). Individual factors may contribute to the cervical cancer development, such as immunogenetic variation. CXCL12/CXCR4 axis is involved in tumor progression and aggressiveness. In the present study, we aimed to investigate a possible association between two single-nucleotide variants (CXCL12 rs1801157 and CXCR4 rs2228014) with HPV infection and cervical cancer development. METHODS: PCR technique was used to test HPV positivity in 424 women, in which the allelic frequency of CXCL12 rs1801157 and CXCR4 rs2228014 was also assessed by PCR-restriction fragment length polymorphism. RESULTS: CXCL12 rs1801157 was associated with HPV infection in the allelic distribution as well in the codominant, dominant and recessive genetic models; as well with squamous intraepithelial lesions (SIL) and CC in the codominant and dominant models. CXCR4 rs2228014 was associated to HPV infection in the codominant model and allelic distribution; as well with SIL/CC in the codominant, dominant and allelic models. Independent associations were found for CXCL12 AA genotype and HPV infection, SIL and CC development, as well as, CXCR4 allele T and HPV infection and CC. The variants interaction analysis demonstrated that the presence of both polymorphisms increases the susceptibility of HPV infection in 10.1 times, SIL (2 times) and CC development in 4.2 times. CONCLUSIONS: This is the first study demonstrating that the interaction of CXCL12 and CXCR4 variants contributes to the increased susceptibility of HPV infection, squamous intraepithelial lesions and cervical cancer development.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Alelos , Carcinogênese/genética , Quimiocina CXCL12/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Receptores CXCR4/genética , Neoplasias do Colo do Útero/genética
17.
Cells ; 12(1)2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36611878

RESUMO

This study aimed to verify the role of TGFB1 variants (c.-1638G>A, c.-1347C>T, c.29C>T, and c.74G>C) in HPV infection susceptibility and cervical lesions development, and their impact on TGFB1 cervical and plasma levels. TGFB1 genotypes were assessed with PCR-RFLP and haplotypes were inferred for 190 HPV-uninfected and 161 HPV-infected women. TGFB1 levels were determined with immunofluorimetric assay. Case-control analyses were performed with logistic regression adjusted for possible confounders. Women carrying -1347TT or -1347CT+TT as well as those with 29CT, 29CC, or 29CT+CC were more likely to have HPV than -1347CC and 29TT carriers, respectively. Regarding haplotypes, the most frequent were *4 (GCTG) and *3 (GTCG). Women *4/*4 were less likely to have HPV than those with no *4 copy. Comparing the inheritance of *3 and *4, carriers of *3/*4 or *3/*3 were more susceptible to HPV than *4/*4. The TGFB1 plasma and cervical levels were higher in the infected patients. Plasma levels were also higher in infected women with low-grade lesions. HPV-infected patients carrying *3/Other and *3/Other+*3/*3 presented lower TGFB1 plasma levels than those with no copy of *3. TGFB1 variants could contribute to the comprehension of the TGFB1 role in HPV-caused cervical disease.


Assuntos
Infecções por Papillomavirus , Humanos , Feminino , Haplótipos/genética , Infecções por Papillomavirus/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta1/genética
18.
Exp Mol Pathol ; 124: 104716, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34767808

RESUMO

Human Papillomavirus (HPV) is the most frequent etiological agent sexually transmitted. In the context of the immune response, NF-kB pathway plays an important role controlling the expression of several genes essential to cellular activity and structural and/or functional changes in components of this pathway can promote the development of several tumors. Thus, the study purpose was to evaluate the influence of NFKB1 rs28362491 and NFKBIA rs696 genetic variants on HPV infection and cervical lesions development. In this study 334 patients were recruited, of whom 48.8% (n = 163) were HPV infected, and considered our case group. HPV-DNA was detected by polymerase chain reaction (PCR) and the genetic variants were assessed in blood cells and tumor tissues paraffin embedded samples through restriction fragment length polymorphism analysis. Among women who were recruited for this study who were infected, 37.4% presented precursor lesions and 16.8% were diagnosed with cervical cancer (CC). The present study did not observe significant effects of the interaction between such genetic variants on HPV infection, nor on the development of lesions and progression to CC. Further studies will be important to investigate if under some circumstance the NFKB1 rs28362491 and NFKBIA rs696 genetic variants influence the progression of HPV-associated lesions.


Assuntos
Inibidor de NF-kappaB alfa/genética , Infecções por Papillomavirus/patologia , Adulto , Estudos de Coortes , Estudos Transversais , DNA Viral/análise , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/patologia
19.
Artigo em Português | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-1421109

RESUMO

Objetivo: Analisar a associação entre variáveis relacionadas à gestão de serviços da Atenção Primária à Saúde e características profissionais no início da pandemia da COVID-19. Material e Método: Estudo transversal, tipo survey, realizado por meio de amostragem por conveniência, a partir do método bola de neve, que contemplou 259 profissionais de saúde da APS do Mato Grosso do Sul e São Paulo, atuantes na gestão e na assistência direta, no período inicial da pandemia. Foi aplicado um questionário semiestruturado virtual. As variáveis "estado", "categoria profissional" e "função exercida" foram consideradas variáveis independentes; as variáveis "oferta de recursos humanos e de materiais" e "apoio da gestão", variáveis dependentes. A associação entre variáveis foi avaliada por meio do teste exato de Fisher. O nível de significância adotado foi 0,05. O projeto foi aprovado pelo comitê de ética através do CAAE n.° 31493920.8.0000.0021. Resultados: Os profissionais percebem fragilidades na oferta de recursos materiais e humanos e insatisfação quanto à logística no que se refere à gestão municipal (40%). A percepção quanto a logística de fluxos e transporte foi diferente entre profissionais que atuam na assistência e na gestão (p ≤ 0,05). Conclusão: Os profissionais percebem a gestão municipal da pandemia, em diferentes aspectos, como inadequada. Faz-se necessária a implementação de políticas públicas e de gestão que valorizem os serviços de APS e seus profissionais, garantindo condições adequadas de trabalho, o que refletirá em um melhor atendimento e satisfação para os usuários do Sistema Único de Saúde.


Objective: To analyze the association between variables related to the management of Primary Health Care (PHC) services and professional characteristics at the beginning of the COVID-19 pandemic. Materials and Methods: Cross-sectional, survey-type study, carried out through convenience sampling, using the snowball method, which included 259 PHC professionals in the states of Mato Grosso do Sul and São Paulo, working in management and direct care in the initial period of the pandemic. A virtual semi-structured questionnaire was applied. The variables "state", "professional category" and "function" were considered independent variables and "supply of human and material resources", as well as "management support" were considered dependent variables. The association between variables was assessed using Fisher's exact test. The significance level adopted was 0.05. The project was approved by the ethics committee with the code number 31493920.8.0000.0021. Results: Health professionals perceive weaknesses in the supply of material and human resources, as well as dissatisfaction with logistics regarding municipal management (40%). The perception of flow and transport logistics also varied among professionals working in care and management (p≤0.05). Conclusion: Professionals perceive municipal management of the pandemic, in different aspects, as inadequate. Therefore, it is necessary to implement public and management policies that value PHC services and their professionals, ensuring adequate working conditions, which can reflect in better care and satisfaction for users of the Brazilian Unified Health System.


Objetivo: Analizar la asociación entre variables relacionadas con la gestión de los servicios de Atención Primaria de Salud (APS) y las características profesionales al inicio de la pandemia de COVID-19. Material y Método: Estudio transversal, de tipo survey, realizado por muestreo de conveniencia, utilizando el método de bola de nieve, que incluyó a 259 profesionales de salud de la APS en los estados de Mato Grosso do Sul y São Paulo, quienes se desempeñaban en gestión y atención directa durante el período inicial de la pandemia. Se aplicó un cuestionario virtual semiestructurado. Las variables "estado", "categoría profesional" y "función desempeñada" fueron consideradas variables independientes y la "oferta de recursos humanos y materiales", además del "apoyo a la gestión" se consideraron variables dependientes. La asociación entre variables se evaluó mediante la prueba exacta de Fisher. El nivel de significación adoptado fue de 0,05. El proyecto fue aprobado por el comité de ética a través del código CAAE n.° 31493920.8.0000.0021. Resultados: Los profesionales perciben debilidades en la oferta de recursos materiales y humanos e insatisfacción con la logística relativa a la gestión municipal (40%). La percepción del flujo y la logística del transporte fue diferente entre los profesionales que se desempeñan en el cuidado y la gestión (p≤0,05). Conclusión: Los profesionales perciben la gestión municipal de la pandemia, en diferentes aspectos, como inadecuada. Es necesario implementar políticas públicas y de gestión que valoricen los servicios de APS y a sus profesionales, asegurando condiciones de trabajo adecuadas que se reflejen en una mejor atención y satisfacción de los usuarios del Sistema Único de Salud de Brasil.

20.
Invest. educ. enferm ; 39(3): 77-90, 15 octubre del 2021. Tab
Artigo em Inglês | LILACS, BDENF - Enfermagem, COLNAL | ID: biblio-1348098

RESUMO

Objective: To determine the main changes that took place in the daily lives of students in the health area during the beginning of the Covid-19 pandemic in Brazil. Method: This is a cross-sectional study, carried out from May to June 2020, with 1786 students over 18 years old, regularly enrolled in health courses at higher education institutions in five regions of Brazil. Sampling was by convenience, typified as snowball. In order to collect data, an instrument to describe the sociodemographic profile and the daily lives of students during the pandemic period was used, which was applied via a digital platform on the web. Results: The main changes that took place in the daily lives of academic students in the health area in the face of the Covid-19 pandemic in Brazil are related to lower productivity; difficulty concentrating; increased hours of sleep, use of electro-electronic equipment and weight; poorer quality of food; higher consumption of food, legal and illegal substances and medications (mainly analgesics, anxiolytics and antidepressants); less interest in personal appearance; and greater contact with relatives. Regarding emotional changes, it should be underlined the complaints of anxiety, stress, anguish, confusion, helplessness and depression. Conclusion: During the beginning of the Covid-19 pandemic in Brazil, the students in the health area experienced several changes in their daily lives, which deserve special attention from higher education institutions and health systems, envisioning interventions to minimize health risks to this population.


Objetivo. Determinar los principales cambios ocurridos en la vida cotidiana de los estudiantes del área de la salud durante el inicio de la pandemia de COVID-19 en Brasil. Métodos. Estudio transversal realizado a 1786 estudiantes mayores de 18 años, regularmente matriculados en cursos del área de la salud en instituciones de enseñanza superior en cinco regiones de Brasil. El muestreo fue por conveniencia del tipo bola de nieve. Para la recolección de datos se utilizó un instrumento para describir el perfil sociodemográfico y la rutina de los estudiantes al inicio del periodo de la pandemia, el cual se aplicó a partir de una plataforma digital en la web. Resultados. Los principales cambios ocurridos diariamente están relacionados con la menor productividad; la dificultad de concentración, el aumento en las horas de sueño, del peso y el uso de dispositivos electrónicos, la inadecuada alimentación, el mayor consumo de alimentos, el uso sustancias lícitas e ilícitas y medicamentos (principalmente analgésicos, ansiolíticos y antidepresivos), el menor interés por la apariencia personal y el menor contacto con los familiares. En cuanto a los cambios emocionales, se presentó en mayor medida ansiedad, estrés, angustia, confusión, impotencia y depresión. Conclusión. Los estudiantes de salud durante el inicio de la pandemia de COVID-19 en Brasil experimentaron varios cambios en su vida cotidiana, que merecen una atención especial por parte de las instituciones de educación superior y los sistemas de salud, con el objetivo de realizar intervenciones para minimizar los riesgos para la salud de esta población.


Objetivo. Determinar as principais mudanças ocorridas no quotidiano de estudantes da área de saúde durante o início da pandemia da Covid-19 no Brasil. Métodos. Estudo transversal, realizado no período de maio a junho de 2020 com 1786 estudantes com mais de 18 anos, regularmente matriculados em cursos da área da saúde em instituições de nível superior de cinco regiões do Brasil. A amostragem foi por conveniência, do tipo bola de neve. Para coleta de dados, utilizou-se um instrumento para descrever o perfil sociodemográfico e a rotina dos estudantes durante o período de pandemia, que foi aplicado via plataforma digital na web. Resultados. As principais mudanças ocorridas no quotidiano dos acadêmicos da área da saúde frente à pandemia da Covid-19 no Brasil estão relacionadas à menor produtividade; dificuldade de concentração; aumento de horas de sono, do peso, de uso de equipamentos eletroeletrônicos; pior qualidade da alimentação; maior consumo de alimentos, substâncias lícitas e ilícitas e medicamentos (principalmente analgésicos, ansiolíticos e antidepressivos); menor interesse pela aparência pessoal; e maior contato com familiares. Em relação às alterações emocionais, destacam-se maiores queixas de ansiedade, estresse, angústia, confusão, impotência e depressão. Conclusão. Os estudantes da área de saúde durante o início da pandemia da Covid-19 no Brasil vivenciaram diversas mudanças no quotidiano, as quais merecem atenção especial por parte das instituições de ensino superior e dos sistemas de saúde, vislumbrando-se intervenções para minimizar os riscos à saúde desta população


Assuntos
Humanos , Estudantes de Ciências da Saúde , COVID-19 , Pandemias
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