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1.
An Acad Bras Cienc ; 96(3): e20230224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38896739

RESUMO

Between 2017 and 2021, the Brazilian Unified Health System (BUHS) administered a total of 527,903,302 doses of immunizations. Each immunization results in the presence of a residual volume (RV) due to syringe dead space (DS). The International Organization for Standardization 7886-1 allows a DS of up to 0.07mL in sterile single-use hypodermic syringes with volumes less than 5mL. This study aims to quantify the DS of immunization devices used in Brazil, study the best combinations of needles and syringes to minimize RV, estimate the number of wasted doses from 2017 to 2021, and evaluate the impact on the BUHS. Pneumococcal 10 vaccine with a 25x6mm needle and a regular 1mL syringe exhibited a significantly higher average RV (0.0826mL) and waste rate (14.42%). It was observed that for some intramuscular vaccines, there is less waste when using a 20x5.5mm needle compared to a 25x6mm needle. The use of syringes with plunger stoppers that penetrate the syringe barrel, denoted as low dead space syringes, results in less RV and an estimated difference in the waste rate of approximately 10% compared to the regular syringe. The estimated number of wasted doses from 2017 to 2021 by BUHS is approximately 32 million doses.


Assuntos
Vacinas , Brasil , Humanos , Seringas , Agulhas , Programas Nacionais de Saúde
2.
Int J Mol Sci ; 25(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38542221

RESUMO

HIV-associated neurocognitive disorders (HAND) affect 15-55% of HIV-positive patients and effective therapies are unavailable. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated an increased expression of cathepsin B (CATB), a lysosomal protease, in monocytes and post-mortem brain tissues of women with HAND. Increased CATB release from HIV-infected MDM leads to neurotoxicity, and their secretion is associated with NF-κB activation, oxidative stress, and lysosomal exocytosis. Cannabinoid receptor 2 (CB2R) agonist, JWH-133, decreases HIV-1 replication, CATB secretion, and neurotoxicity from HIV-infected MDM, but the mechanisms are not entirely understood. We hypothesized that HIV-1 infection upregulates the expression of proteins associated with oxidative stress and that a CB2R agonist could reverse these effects. MDM were isolated from healthy women donors (n = 3), infected with HIV-1ADA, and treated with JWH-133. After 13 days post-infection, cell lysates were labeled by Tandem Mass Tag (TMT) and analyzed by LC/MS/MS quantitative proteomics bioinformatics. While HIV-1 infection upregulated CATB, NF-κB signaling, Nrf2-mediated oxidative stress response, and lysosomal exocytosis, JWH-133 treatment downregulated the expression of the proteins involved in these pathways. Our results suggest that JWH-133 is a potential alternative therapy against HIV-induced neurotoxicity and warrant in vivo studies to test its potential against HAND.


Assuntos
Canabinoides , Infecções por HIV , HIV-1 , Humanos , Feminino , NF-kappa B/metabolismo , Proteômica , Espectrometria de Massas em Tandem , Macrófagos/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Estresse Oxidativo , Exocitose , Lisossomos/metabolismo
3.
Int J Mol Sci ; 25(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38791465

RESUMO

Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico. Following IRB approval, a total of 95 unvaccinated men and women aged 21-71 years old were recruited in Puerto Rico from 2020-2021. Plasma samples were collected from COVID-19-positive subjects (n = 39) and COVID-19-negative individuals (n = 56) during acute disease. COVID-19-positive individuals were stratified based on symptomatology as follows: mild (n = 18), moderate (n = 13), and severe (n = 8). Quantitative proteomics was performed in plasma samples using tandem mass tag (TMT) labeling. Labeled peptides were subjected to LC/MS/MS and analyzed by Proteome Discoverer (version 2.5), Limma software (version 3.41.15), and Ingenuity Pathways Analysis (IPA, version 22.0.2). Cytokines were quantified using a human cytokine array. Proteomics analyses of severely affected COVID-19-positive individuals revealed 58 differentially expressed proteins. Cadherin-13, which participates in synaptogenesis, was downregulated in severe patients and validated by ELISA. Cytokine immunoassay showed that TNF-α levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Ricans.


Assuntos
COVID-19 , Proteômica , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/virologia , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Feminino , Masculino , Adulto , Idoso , Proteômica/métodos , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Adulto Jovem , Citocinas/sangue , Citocinas/metabolismo , Espectrometria de Massas em Tandem
4.
Int J Mol Sci ; 24(10)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37240166

RESUMO

Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM] + cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.


Assuntos
Líquidos Iônicos , Tiroxina , Tiroxina/síntese química , Tiroxina/farmacocinética , Tiroxina/toxicidade , Disponibilidade Biológica , Solubilidade , Líquidos Iônicos/síntese química , Líquidos Iônicos/farmacocinética , Líquidos Iônicos/toxicidade , Células L , Animais , Camundongos , Permeabilidade
5.
Molecules ; 28(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37049922

RESUMO

Resveratrol (RSV), a naturally occurring metabolite, is widely used in skincare products, but its hydrophobicity impairs its own incorporation into cosmetic formulations. RSV-GS is a synthetic hydrophilic sulfated glycosylated derivative inspired by marine natural products that present a lower cytotoxicity than RSV while exhibiting similar levels of bioactivity. Herein, we predict the skin sensitization potential of this new compound using an in vitro approach based on the OECD 442E guideline. Furthermore, the anti-allergic potential of RSV-GS was also disclosed. The monocyte THP-1 cell line was stimulated with RSV and RSV-GS in the presence or absence of the extreme skin allergen 1-fluoro-2,4-dinitrobenzene (DNFB). The results demonstrated that RSV-GS alone (500 µM) evoked a relative fluorescence index (RFI) lower than the thresholds established by the OECD guideline for CD54 (200%) and CD86 (150%), indicating the absence of a skin sensitization potential. Interestingly, in the presence of the skin allergen DNFB, RSV-GS exhibited the ability to rescue the DNFB-induced maturation of THP-1 cells, with RFI values lower than those for RSV, suggesting the potential of RSV-GS to mitigate skin sensitization evoked by allergens and, consequently, allergic contact dermatitis. These results open new avenues for the use of RSV-GS as a safe and anti-allergic active cosmetic ingredient.


Assuntos
Antialérgicos , Resveratrol/farmacologia , Sulfatos , Dinitrofluorbenzeno , Alérgenos
6.
Indian J Microbiol ; 63(4): 588-595, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38031606

RESUMO

Human papillomavirus (HPV) is a virus with a DNA structure that specifically targets squamous epithelial cells. In individuals with a healthy immune system, HPV infection is typically resolved naturally, leading to spontaneous regression. However, when the viral genetic material integrates into the host DNA, it can disrupt the immune response and eventually give rise to neoplastic manifestations. Remarkably, HPV infection appears to activate a protein called Stimulator of Interferon genes (STING), which contributes to the infiltration of Treg Foxp3 + cells. This cellular response acts as a predisposing factor in patients with HPV, potentially exacerbating the progression of the infection. The STING is versatile in different circumstances and can play a role in the immune response as an anti-tumour therapeutic target in HPV-related carcinogenesis. The function of Th17 cells is ambiguous, depending on the microenvironment in the tumour. In this study, 46 biopsies of the uterine cervix of human immunodeficiency virus (HIV) positive patients were divided into three groups: I-cervicitis (10); II-low-grade intraepithelial neoplasia (26); III-moderate or severe intraepithelial neoplasia (10) and it was performed an immunohistochemical technique with the specific antibodies to HPV, CD123, STING and IL17. Immunostained cells were quantified and statistically analysed. Antigens of HPV were detected in the cervical intraepithelial neoplasia (CIN) groups and were absent in cervicitis group. The expression of CD123 was positive in 10.87% of the casuistic, with no statistical difference among groups. STING was present in the three groups. Group 1 presented an area fraction that varied from 3 to 20%, group 2 presented a variation of 3-23% and group 3 presented an area fraction between 4 and 12%. Cells expressing IL17 were present in three groups, more frequent in cervicitis. Considering that the casuistic is composed of women carrying HIV, this infectious agent could influence the numerical similarities of the cells studied among three groups, even in the absence of HPV.


Stimulator of Interferon genes protein (STING) is versatile in different mechanisms in the immune response and may be a target in HPV-related carcinogenesis. Through immunohistochemistry it was detected IL17 in cervicitis and lesions with HPV. Also, CD123 + plasmacytoid cells seems to play a role both in cervicitis and lesions mediated by HPV.

7.
Microbiology (Reading) ; 168(10)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36201337

RESUMO

Staphylococcus aureus is responsible for severe skin and respiratory infections and food poisoning, resulting in hospitalizations and high morbidity worldwide. Staphylococci have extensive virulence mechanisms and antimicrobial resistance that pose a global challenge to contain the spread of infectious outbreaks. Antimicrobials are used as growth promoters, and for prevention and treatment of infections in animals that provide us with food. The improvement of animal health is undeniable, but the selection of multidrug-resistant strains that can spread resistance genes among microorganisms is undesirable. The administration of sublethal doses of antimicrobials in farm animals causes stress to Staphylococci inducing the formation of a complex extracellular polymeric structure called biofilm. Such a structure may favor the persistence of infection by disseminating antimicrobial-resistant strains that can be consumed in contaminated food of animal origin. In ruminant mastitis and hospitals, the potential of the biofilm structure in the persistence of infections, especially those caused by S. aureus, has already been demonstrated, as well as its role as a source of resistant genes. In the meat production chain, the potential for persistent contamination by biofilm structure is evidently a worrying health risk . This review brings together studies demonstrating that biofilm production facilitates the exchange of mobile genetic elements and random mutations in S. aureus strains within the structure. This contributes to the emergence of more resistant clonal complexes and, with biofilm support, persists in the meat production chain.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Farmacorresistência Bacteriana/genética , Feminino , Carne , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/epidemiologia , Staphylococcus , Staphylococcus aureus/genética
8.
Mar Drugs ; 20(5)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35621966

RESUMO

The growing number of infectious diseases around the world threatens the effective response of antibiotics, contributing to the increase in antibiotic resistance seen as a global health problem. Currently, one of the main challenges in antimicrobial drug discovery is the search for new compounds that not only exhibit antimicrobial activity, but can also potentiate the antimicrobial activity and revert antibiotics' resistance, through the interference with several mechanisms, including the inhibition of efflux pumps (EPs) and biofilm formation. Inspired by macroalgae brominated bromophenol BDDE with antimicrobial activity, a series of 18 chalcone derivatives, including seven chalcones (9-15), six dihydrochalcones (16-18, and 22-24) and five diarylpropanes (19-21, and 25 and 26), was prepared and evaluated for its antimicrobial activity and potential to fight antibiotic resistance. Among them, chalcones 13 and 14 showed promising antifungal activity against the dermatophyte clinical strain of Trichophyton rubrum, and all compounds reversed the resistance to vancomycin in Enterococcus faecalis B3/101, with 9, 14, and 24 able to cause a four-fold decrease in the MIC of vancomycin against this strain. Compounds 17-24 displayed inhibition of EPs and the formation of biofilm by S. aureus 272123, suggesting that these compounds are inhibiting the EPs responsible for the extrusion of molecules involved in biofilm-related mechanisms. Interestingly, compounds 17-24 did not show cytotoxicity in mouse embryonic fibroblast cell lines (NIH/3T3). Overall, the results obtained suggest the potential of dihydrochalcones 16-18 and 22-24, and diarylpropanes 19-21, 25 and 26, as hits for bacterial EPs inhibition, as they are effective in the inhibition of EPs, but present other features that are important in this matter, such as the lack of antibacterial activity and cytotoxicity.


Assuntos
Anti-Infecciosos , Chalcona , Chalconas , Micoses , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Chalcona/farmacologia , Chalconas/farmacologia , Fibroblastos , Camundongos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Relação Estrutura-Atividade , Vancomicina/farmacologia
9.
Cryobiology ; 101: 95-104, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33974836

RESUMO

This work aimed at evaluating the potential of using natural deep eutectic systems (NADES) as cryoprotectant agents (CPAs). Several combinations between natural primary metabolites that have been identified in animals that live in extreme cold climates were prepared. All systems showed very little cytoxicity towards L929 cells at concentrations high as 1-2 M. Moreover, this cell line was highly tolerant to 10% (w/v) of NADES when compared to Me2SO. To test NADES as CPAs, two cell lines were used, L929 and HacaT cells. After freeze/thawing cycle, it was possible to observe that for L929 cells, NADES presented similar behaviour to Me2SO. For Hacat cell line a significant improvement on post-thawing recovery was observed. Moreover, the results presented herein showed that NADES do not need to be removed from the freezing media after thawing the cells, which is a great advantage of these materials. Additionally, we have shown that NADES can act as CPA when cells are frozen at -20 °C. In overall, the results demonstrate the high potential of NADES to be used in cryobiology as alternative CPAs.


Assuntos
Criopreservação , Crioprotetores , Animais , Linhagem Celular , Criopreservação/métodos , Crioprotetores/farmacologia , Congelamento , Solventes
10.
Lasers Med Sci ; 36(4): 903-912, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33113075

RESUMO

To assess the effectiveness of photobiomodulation therapy (PBMT) in the oral health-related quality of life (OHRQoL) of patients with head and neck cancer undergoing radiotherapy (RT), using the Oral Health Impact Profile-14 (OHIP-14) and the Patient-Reported Oral Mucositis (OM) Symptoms Scale (PROMS), and to correlate OM degree with the PROMS and OHIP-14 scores. Forty-eight patients undergoing RT for head and neck cancer were randomly assigned into two groups: PBMT group (n = 25)-daily PBMT associated with a preventive oral care program (POCP); and control group (n = 23)-receiving POCP exclusively. OHRQoL was assessed using the PROMS and OHIP-14 questionnaires. OM degrees were classified according to the World Health Organization and the National Cancer Institute scales. Assessments were performed at the 1st, 7th, 14th, 21st, and 30th RT sessions. PBMT was effective in preventing and treating severe OM. Both groups showed increased OHRQoL impacts throughout the RT sessions; however, higher impacts were observed in the control group, mainly at the final stage of treatment (21st and 30th RT sessions). Significant correlations were found between the severity of OM and PROMS scores in the total sample and the control group at all RT periods. PROMS and OM scores were positive correlated at 14th, 21st, and 30th RT sessions in the control group, suggesting that this instrument is useful in classifying OM. PBMT was effective in treating and preventing severe OM and OM-related symptoms, and with consequent positive impacts in OHRQoL in head and neck patients undergoing RT. The PROMS scale was helpful instrument for assessment of the severity of OM. Brazilian Clinical Trials database (ReBEC - RBR-5h4y4n), registered in Aug, 24th 2017.


Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Luz de Baixa Intensidade , Estomatite/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estomatite/etiologia , Estomatite/radioterapia , Inquéritos e Questionários
11.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443357

RESUMO

In this work, we propose the utilization of scCO2 to impregnate ibuprofen into the mcl-PHA matrix produced by Pseudomonas chlororaphis subs. aurantiaca (DSM 19603). The biopolymer has adhesive properties, is biocompatible and has a melting temperature of 45 °C. Several conditions, namely, pressure (15 and 20 MPa) and impregnation time (30 min, 1 h and 3 h) were tested. The highest ibuprofen content (90.8 ± 6.5 mg of ibuprofen/gPHA) was obtained at 20 MPa and 40 °C, for 1 h, with an impregnation rate of 89 mg/(g·h). The processed mcl-PHA samples suffered a plasticization, as shown by the decrease of 6.5 °C in the Tg, at 20 MPa. The polymer's crystallinity was also affected concomitantly with the matrices' ibuprofen content. For all the impregnation conditions tested the release of ibuprofen from the biopolymer followed a type II release profile. This study has demonstrated that the mcl-PHA produced by P. chlororaphis has a great potential for the development of novel topical drug delivery systems.


Assuntos
Dióxido de Carbono/química , Portadores de Fármacos/química , Ibuprofeno/química , Poli-Hidroxialcanoatos/química , Adesividade , Liberação Controlada de Fármacos , Temperatura
12.
Support Care Cancer ; 28(9): 4263-4273, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31900618

RESUMO

OBJECTIVE: To evaluate the occurrence and severity of oral complications, number of radiotherapy (RT) interruptions and quality of life (QoL) in a population of head and neck cancer patients receiving a preventive oral care program (POCP) and photobiomodulation therapy (PBMT). METHODS: Prospective cohort of 61 head and neck cancer patients undergoing radiochemotherapy were monitored and submitted to a POCP that included oral hygiene and plaque control, removal of infection foci, dental restorations, periodontal therapy, fluorotherapy, oral hydration, and denture removal at night, combined with daily PBMT. Outcomes included occurrence of adverse effects such as severity of oral mucositis (OM) and oral symptoms (pain, solid and fluid dysphagia, odynophagia, dysgeusia), quality of life impacts, and interruptions of radiotherapy (RT) due to symptoms. Disease-free and overall survival rates were evaluated. RESULTS: There was a significant improvement in oral health conditions between initial assessment and the two longitudinal assessments (p < 0.05), which indicates that the POCP was effective for plaque control and reduction of gingival inflammation. All participants were free of OM at the beginning of the RT regimen and only 45.9% after the 7th session, and few patients ranked the highest score of OM. For all symptoms related to OM, there was a progressive increase of severity until the 14th RT session, which remained stable until the completion of the RT regimen. The same effect was observed for the quality of life measures. Discontinued RT due to OM occurred in only three patients (5%), and the maximum duration was 10 days. The overall survival rate was 77% and disease-free survival was 73.8%. Lower survival time was observed for patients with no response to RT (p < 0.01). CONCLUSIONS: The findings of this study suggest a positive effect of an oral preventive care program for head and neck cancer patients submitted to RT. The PBMT associated with a rigorous POCP resulted in satisfactory control of oral adverse effects, reduction of quality of life impacts, and interruption of RT regimen due to severe OM.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Doenças da Boca/etiologia , Doenças da Boca/prevenção & controle , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças da Boca/induzido quimicamente , Saúde Bucal , Higiene Bucal/métodos , Estudos Prospectivos , Qualidade de Vida , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle
13.
Mar Drugs ; 17(2)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30678253

RESUMO

Macroalgae have been reported as an important source of halogenated aromatic secondary metabolites, being the majority of these derivatives isolated from red algae. Halophenols and haloindoles are the most common haloaryl secondary metabolites isolated from these marine organisms. Nevertheless, some halogenated aromatic sesquiterpenes and naphthalene derivatives have also been isolated. Most of these secondary metabolites showed interesting biological activities, such as antitumor, antimicrobial, antidiabetic, and antioxidant. This review describes in a systematic way the distribution and natural occurrence of halogenated aromatic secondary metabolites from extracts of red, brown, and green algae, as well as biological activities reported for these compounds.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/farmacologia , Alga Marinha/química , Alga Marinha/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Clorófitas/química , Clorófitas/metabolismo , Estrutura Molecular , Phaeophyceae/química , Phaeophyceae/metabolismo , Rodófitas/química , Rodófitas/metabolismo
14.
J Assist Reprod Genet ; 36(7): 1471-1479, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104291

RESUMO

PURPOSE: Infertility is estimated to affect 15% of couples, having chromosome abnormalities an important role in its etiology. The main objective of this work was to access the reproductive success of ART in infertile couples with chromosomal abnormalities comparing to a control group with normal karyotype. METHODS: A 7-year retrospective karyotype analysis of infertile couples was done. Data regarding type of infertility, couples' ages, ART performed, and their reproductive success were obtained. Adjusted odds ratio (OR) were used to estimate magnitude of association between the reproductive success and the different groups. RESULTS: We found a prevalence of 7.83% of chromosome abnormalities in our population (233 couples out of 2989). Chromosomal anomalies were found in 82 men (34.75%) and 154 women (65.25%), with low-grade mosaicism being the most prevalent (50.85%), followed by autosomal translocations (17.37%) and sex chromosomes abnormalities (13.56%). Only 2359 couples were treated with ART. There was a non-significant lower reproductive success rate in the cases (OR = 0.899, p = 0.530) with IVF providing the higher success rate. In general, female carriers of chromosome anomalies had a higher success rate, although not significant. CONCLUSION: Although the differences regarding success rate between groups were not found statistically significant, we still advocate that cytogenetic analysis should be performed routinely in all infertile couples namely before ART. This might help deciding the best treatment options including Preimplantation Genetic Testing for aneuploidies or structural rearrangements and minimize the risk of transmission of anomalies to the offspring.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/epidemiologia , Infertilidade Masculina/genética , Técnicas de Reprodução Assistida , Adulto , Aneuploidia , Aberrações Cromossômicas/classificação , Transtornos Cromossômicos/patologia , Transtornos Cromossômicos/reabilitação , Feminino , Fertilização in vitro , Testes Genéticos , Humanos , Infertilidade Masculina/epidemiologia , Infertilidade Masculina/patologia , Cariotipagem , Masculino , Gravidez , Resultado da Gravidez , Injeções de Esperma Intracitoplásmicas
15.
Methods ; 98: 143-149, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26855377

RESUMO

The vast majority of human protein-coding genes contain up to 90% of non-coding sequence in the form of introns that must be removed from the primary transcripts or pre-mRNAs. Diverse forms of mRNAs encoded from a single gene are created by the differential use of splice sites and alternative splicing is rapidly evolving. Although the kinetic properties of splicing are thought to be critical for proofreading and regulatory mechanisms, tools for making direct experimental measurements of splicing rates are still limited. We recently developed a strategy that permits real-time imaging of fluorescent-labelled introns in single pre-mRNA molecules. Here we describe the software tool that we created for automatic tracking and quantification of intronic fluorescence at the site of transcription in live human cells.


Assuntos
Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Precursores de RNA/genética , Splicing de RNA , RNA Mensageiro/genética , Imagem Individual de Molécula/estatística & dados numéricos , Software , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Éxons , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Íntrons , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia de Fluorescência , Fases de Leitura Aberta , Precursores de RNA/metabolismo , Sítios de Splice de RNA , RNA Mensageiro/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Imagem Individual de Molécula/métodos , Proteína Vermelha Fluorescente
16.
Cureus ; 16(7): e64412, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39130966

RESUMO

We report a case of a 16-year-old male with tricuspid valve infective endocarditis caused by Aggregatibacter aphrophilus and complicated by pulmonary septic embolisms. Multiple antimicrobial therapy was unsuccessful and surgical management was required. In this report, the authors highlight the importance of a high index of suspicion regarding the diagnosis of endocarditis and its possible complications.

17.
Eur J Pharm Biopharm ; 198: 114276, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582179

RESUMO

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.


Assuntos
Oftalmopatias , Degeneração Macular , Humanos , Olho/metabolismo , Oftalmopatias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Degeneração Macular/tratamento farmacológico
18.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38399436

RESUMO

Chemists in the medicinal chemistry field are constantly searching for alternatives towards more sustainable and eco-friendly processes for the design and synthesis of drug candidates. The pharmaceutical industry is one of the most polluting industries, having a high E-factor, which is driving the adoption of more sustainable processes not only for new drug candidates, but also in the production of well-established active pharmaceutical ingredients. Deep eutectic systems (DESs) have emerged as a greener alternative to ionic liquids, and their potential to substitute traditional organic solvents in drug discovery has raised interest among scientists. With the use of DESs as alternative solvents, the processes become more attractive in terms of eco-friendliness and recyclability. Furthermore, they might be more effective through making the process simpler, faster, and with maximum efficiency. This review will be focused on the role and application of deep eutectic systems in drug discovery, using biocatalytic processes and traditional organic chemical reactions, as new environmentally benign alternative solvents. Furthermore, herein we also show that DESs, if used in the pharmaceutical industry, may have a significant effect on lowering production costs and decreasing the impact of this industry on the quality of the environment.

19.
J Child Orthop ; 18(4): 386-392, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39100978

RESUMO

Purpose: Our purpose was to analyze the impact of Pavlik Harness treatment on children motor skills development, comparing to a control group. Methods: A total of 121 children were included: 55 cases (children with Developmental Dysplasia of the Hip) and 66 healthy controls. Cases were recruited from 2017 to 2021 and followed up to 2022. Controls (healthy children without orthopedic pathology) were recruited from 2020 to 2022. The primary endpoint was the time of achievement of three gross motor milestones (sitting without support, hands-and-knees crawling, and walking independently). Results: The groups had no differences regarding sex distribution, gestational age, birth weight, and rate of twin pregnancy. The prevalence of positive family history of Development Dysplasia of the Hip (20.0% vs 3.0%, p < 0.003), breech presentation (38.2% vs 1.5%, p < 0.001), and C-section delivery (60.0% vs 19.7%, p < 0.001) was significantly higher in Development Dysplasia of the Hip group. Children with Development Dysplasia of the Hip achieved the three gross milestones evaluated 1 month later than healthy controls, although this was not statistically significant (p = 0.133 for sitting, p = 0.670 for crawling, and p = 0.499 for walking). Conclusion: Children with Development Dysplasia of the Hip, treated by Pavlik harness, do not have significant delays in motor skills acquisition.

20.
Pediatr Infect Dis J ; 43(3): e106-e108, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241651

RESUMO

An increase in invasive group A Streptococcus infections was reported in 2022, associated with intense respiratory virus circulation. We describe a marked increase of noninvasive group A Streptococcus infections. Although the rise coincided with epidemics of respiratory syncytial virus and influenza, it continued after detection of these viruses fell to low levels, suggesting that other factors have contributed to this epidemiologic change.


Assuntos
Epidemias , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Estreptocócicas , Humanos , Influenza Humana/complicações , Streptococcus pyogenes , Estações do Ano , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/complicações
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