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1.
Immunity ; 50(1): 166-180.e7, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30650375

RESUMO

Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.


Assuntos
Neoplasias Colorretais/imunologia , Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucina-1/metabolismo , Neutrófilos/imunologia , Salmonelose Animal/imunologia , Salmonella/imunologia , Animais , Carcinogênese , Células Cultivadas , Humanos , Interleucina-1/genética , Interleucina-1/imunologia , Interleucinas/metabolismo , Camundongos , Camundongos Knockout , Neutrófilos/ultraestrutura , Especificidade de Órgãos , Receptores de Interleucina-1/genética , Transdução de Sinais , Microambiente Tumoral , Interleucina 22
2.
Biochemistry (Mosc) ; 89(1): 173-183, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38467553

RESUMO

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.


Assuntos
Antioxidantes , Polifenóis , Antioxidantes/farmacologia , Antioxidantes/química , Polifenóis/farmacologia , Polifenóis/química , Peptídeos/farmacologia , Peptídeos/química , Ácido Gálico/farmacologia , Ácido Gálico/química , Antibacterianos/química
3.
Biochemistry (Mosc) ; 88(11): 1800-1817, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38105200

RESUMO

Currently, nucleic acid therapeutics are actively developed for the treatment and prophylactic of metabolic disorders and oncological, inflammatory, and infectious diseases. A growing number of approved nucleic acid-based drugs evidences a high potential of gene therapy in medicine. Therapeutic nucleic acids act in the cytoplasm, which makes the plasma membrane the main barrier for the penetration of nucleic acid-based drugs into the cell and requires development of special vehicles for their intracellular delivery. The optimal carrier should not only facilitate internalization of nucleic acids, but also exhibit no toxic effects, ensure stabilization of the cargo molecules, and be suitable for a large-scale and low-cost production. Cell-penetrating peptides (CPPs), which match all these requirements, were found to be efficient and low-toxic carriers of nucleic acids. CPPs are typically basic peptides with a positive charge at physiological pH that can form nanostructures with negatively charged nucleic acids. The prospects of CPPs as vehicles for the delivery of therapeutic nucleic acids have been demonstrated in numerous preclinical studies. Some CPP-based drugs had successfully passed clinical trials and were implemented into medical practice. In this review, we described different types of therapeutic nucleic acids and summarized the data on the use of CPPs for their intracellular delivery, as well as discussed, the mechanisms of CPP uptake by the cells, as understanding of these mechanisms can significantly accelerate the development of new gene therapy approaches.


Assuntos
Peptídeos Penetradores de Células , Ácidos Nucleicos , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/metabolismo , Ácidos Nucleicos/metabolismo , Transporte Biológico , Terapia Genética
4.
Biochemistry (Mosc) ; 88(10): 1608-1621, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38105028

RESUMO

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the respiratory tract. Allergic (atopic) asthma is the most common (up to 80% of cases) phenotype developing through the Th2-dependent mechanisms involving cytokines: IL-4, IL-5, IL-9, and IL-13. The genes encoding Th2-cytokines have a mosaic structure (encode exons and introns). Therefore, several mature mRNA transcripts and protein isoforms can be derived from a single mRNA precursor through alternative splicing, and they may contribute to BA pathogenesis. Analysis of the published studies and databases revealed existence of the alternative mRNA transcripts for IL-4, IL-5, and IL-13. The alternative transcripts of IL-4 and IL-5 carry open reading frames and therefore can encode functional proteins. It was shown that not only alternative mRNA transcripts exist for IL-4, but alternative protein isoforms, as well. Natural protein isoform (IL-4δ2) lacking the part encoded by exon-2 was identified. Similarly, alternative mRNA transcript with deleted exon-2 (IL-5δ2) was also identified for IL-5. In this review, we summarize current knowledge about the identified alternative mRNA transcripts and protein isoforms of Th2-cytokinins, first of all IL-4 and IL-5. We have analyzed biological properties of the alternative variants of these cytokines, their possible role in the allergic asthma pathogenesis, and considered their diagnostic and therapeutic potential.


Assuntos
Asma , Citocinas , Humanos , Citocinas/genética , Citocinas/metabolismo , Processamento Alternativo , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Asma/genética , Asma/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Th2/metabolismo , Células Th2/patologia
5.
Med J Malaysia ; 78(6): 830-844, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38031228

RESUMO

INTRODUCTION: Mounting evidence has shown the significant correlation between periodontitis and the development of other comorbidities, such as cardiovascular disease due to periodontopathogenic bacterial migration and colonisation. As the main etiologic agent of periodontitis, the role of Porphyromonas gingivalis (P. gingivalis) has been widely explored as the main culprit and its early detection is crucial to control the exacerbation of diseases. This review aims to identify and summarise all clinical diseases that potentially developed due to the presence of P. gingivalis and discover all its detection methods that have been developed. MATERIALS AND METHODS: Full-text articles of case report, case control, cohort and cross-sectional studies that were published from 1st January 2012 until 30th June 2022, were searched using PubMed, CINAHL and Scopus. Periodontal related diseases were excluded in this review due to its wellknown associated disease with P. gingivalis. A comparison studies of detection methods were also excluded in this review. RESULTS: Out of 612 articles that were screened, only 106 met the eligibility criteria to be selected for further review. Risk of bias was performed using FEAT principles and reviewers' discussion. A total of 21 final articles that were reviewed showed significant correlation with P. gingivalis and were classified into several clinical domains. Twelve out of 13 detection methods showed high sensitivity and specificity with short duration analysis. CONCLUSION: Due to asymptomatic periodontal disease and the high prevalence of P. gingivalis-associated clinical diseases, this review suggests the need for oral public health awareness and early screening for the bacterium detection especially among elderly groups to maintain their quality of life.


Assuntos
Periodontite , Porphyromonas gingivalis , Idoso , Humanos , Estudos Transversais , Periodontite/microbiologia , Qualidade de Vida
6.
Ann Ig ; 34(2): 109-121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35088820

RESUMO

Background: COVID-19 pandemic, with its dramatic impact on society, poses a challenge to Health Pro-motion and to its principles of empowerment, social cohesion and citizens' democratic participation in health policies. In this pressing emergency, public health strategies aimed at preventing the spread of the pandemic have been primarily oriented towards restrictive measures (travel restrictions, use of PPE) in absence of an adequate educational communication, aimed at increasing citizens' knowledge and skills in regard to the emergency context. Aim: To offer a perspective on the Italian situation, in terms of health literacy and life skills in the context of COVID-19 pandemic, aimed not only at identifying deficits, but particularly at determining opportuni-ties and resources (assets) - offered by the peculiar context of crisis - useful to provide citizens with the necessary tools to comprehend the criticalities linked with the emergency and to shape their behaviour to new requirements, in absence of external obligations, as well as to promote future participation of the population - both effective and informed - in a social and political context. Methods: A non-systematic review of literature on the subject of health literacy and social cohesion in emergency contexts has been supported by a qualitative assessment, based on the model of assets and on the Italian condition in the last trimester of 2020. Results: The scarce ability of the population to independently adequate habits and behaviour to new criti-calities required by the risk of infection - as well as the necessity to suspend their empowerment and capa-bility from government authorities to protect public health - has been firstly traced back to a widespread lack of literacy and life skills at a general population level. The current situation of crisis offers a peculiar opportunity of tools, circumstances and receptiveness to highlight such deficits, as well as an intervention on multiple fronts, in order to increase literacy and capability, both on an individual and on a community level, through inclusive and sustainable initiatives. Conclusion: A prevention strategy based on the critical understanding of risk and risk-related criticalities is the only one which can aspire to last over time, while offering an effective tool for the safeguarding of public health, along with an opportunity of being prepared to contrast future emergencies more effectively. The development of such strategies represents one of the most significant contributions Health Promotion can offer in the time of Coronavirus.


Assuntos
COVID-19 , Letramento em Saúde , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Coesão Social
7.
Biochemistry (Mosc) ; 86(3): 290-306, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33838630

RESUMO

Respiratory syncytial virus (RSV) causes severe pathology of the lower respiratory tract in infants, immunocompromised people, and elderly. Despite decades of research, there is no licensed vaccine against RSV, and many therapeutic drugs are still under development. Detailed understanding of molecular and cellular mechanisms of the RSV infection pathology can accelerate the development of efficacious treatment. Current studies on the RSV pathogenesis are based on the analysis of biopsies from the infected patients; however deeper understanding of molecular and cellular mechanisms of the RSV pathology could be achieved using animal models. Mice are the most often used model for RSV infection because they exhibit manifestations similar to those observed in humans (bronchial obstruction, mucous hypersecretion, and pulmonary inflammation mediated by lymphocytes, macrophages, and neutrophils). Additionally, the use of mice is economically feasible, and many molecular tools are available for studying RSV infection pathogenesis at the molecular and cellular levels. This review summarizes new data on the pathogenesis of RSV infection obtained in mouse models, which demonstrated the role of T cells in both the antiviral defense and the development of lung immunopathology. T cells not only eliminate the infected cells, but also produce significant amounts of the proinflammatory cytokines TNFα and IFNγ. Recently, a new subset of tissue-resident memory T cells (TRM) was identified that provide a strong antiviral defense without induction of lung immunopathology. These cells accumulate in the lungs after local rather than systemic administration of RSV antigens, which suggests new approaches to vaccination. The studies in mouse models have revealed a minor role of interferons in the anti-RSV protection, as RSV possesses mechanisms to escape the antiviral action of type I and III interferons, which may explain the low efficacy of interferon-containing drugs. Using knockout mice, a significant breakthrough has been achieved in understanding the role of many pro-inflammatory cytokines in lung immunopathology. It was found that in addition to TNFα and IFNγ, the cytokines IL-4, IL-5, IL-13, IL-17A, IL-33, and TSLP mediate the major manifestations of the RSV pathogenesis, such as bronchial obstruction, mucus hyperproduction, and lung infiltration by pro-inflammatory cells, while IL-6, IL-10, and IL-27 exhibit the anti-inflammatory effect. Despite significant differences between the mouse and human immune systems, mouse models have made a significant contribution to the understanding of molecular and cellular mechanisms of the pathology of human RSV infection.


Assuntos
Modelos Animais de Doenças , Pulmão/patologia , Infecções por Vírus Respiratório Sincicial/etiologia , Animais , Citocinas/imunologia , Humanos , Inflamação , Pulmão/imunologia , Camundongos , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/metabolismo , Linfócitos T/imunologia
8.
Biochemistry (Mosc) ; 86(11): 1489-1501, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34906042

RESUMO

Bronchial asthma is a heterogeneous chronic inflammatory disease of airways. The studies of molecular and cellular mechanisms of bronchial asthma have established that a wide range of immune (T and B cells, eosinophils, neutrophils, macrophages, etc.) and structural (epithelial and endothelial) cells are involved in its pathogenesis. These cells are activated in response to external stimuli (bacteria, viruses, allergens, and other pollutants) and produce pro-inflammatory factors (cytokines, chemokines, metalloproteinases, etc.), which ultimately leads to the initiation of pathological processes in the lungs. Genes encoding transcription factors of the STAT family (signal transducer and activator of transcription), that includes seven representatives, are involved in the cell activation. Recent studies have shown that the transcription factor STAT3 plays an important role in the activation of the abovementioned cells, thus contributing to the development of asthma. In animal studies, selective inhibition of STAT3 significantly reduces the severity of lung inflammation, which indicates its potential as a therapeutic target. In this review, we describe the mechanisms of STAT3 activation and its role in polarization of Th2/Th17 cells and M2 macrophages, as well as in the dysfunction of endothelial cells, which ultimately leads to development of bronchial asthma symptoms, such as infiltration of neutrophils and eosinophils into the lungs, bronchial hyperreactivity, and the respiratory tract remodeling.


Assuntos
Asma/imunologia , Leucócitos/imunologia , Pulmão/imunologia , Fator de Transcrição STAT3/imunologia , Animais , Asma/patologia , Humanos , Leucócitos/patologia , Pulmão/patologia
9.
Med J Malaysia ; 76(5): 672-679, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34508373

RESUMO

OBJECTIVE: The aims of this study are to measure the psychometric properties of the newly developed preliminary version of hearing impairment inventory for religious duties for Muslim adults, i.e., the Inventori Persepsi Bagi Muslim Yang Memiliki Masalah Pendengaran (IPM3P), and to produce a final version of IPM3P. METHODS: The preliminary version of IPM3P that is used to investigate the perception of Muslim adults with hearing impairment towards Islamic understanding and practice has been tested in this study. The preliminary version of IPM3P consists of three domains (obligation, practice, and difficulty) with 59 items in total. Four phases of validity and reliability testing involved were: i) Content validation, ii) Pretesting, face validity and proofreading, iii) Pilot study, and iv) Psychometric evaluation. RESULTS: The final version of IPM3P consists of 36 items. The findings from the present study suggest that the final version of IPM3P has excellent psychometric properties manifested by: i) good content validity, ii) excellently pretested, iii) good face validity, iv) good construct validity shown by principal component analysis and convergent validity, and v) good discriminant validity showed by divergent validity. CONCLUSION: IPM3P shows good potential to be used as a tool in investigating perception of Muslim adults towards Islamic understanding and practice.


Assuntos
Perda Auditiva , Islamismo , Adulto , Humanos , Malásia , Percepção , Projetos Piloto , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
Med J Malaysia ; 76(5): 680-684, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34508374

RESUMO

INTRODUCTION: Emotion Regulation Checklist (ERC) has been used globally and translated to several languages, including Brazilian Portuguese, Italian and Persian. The aim of this study is to translate and validate ERC to the Malay language and to measure the reliability and validity of the translated version of this scale among Malaysian parents. METHODS: This study involved forward and back translation method. The translated questionnaire was then pretested and piloted among 10 parents and 50 participants, respectively. The procedure was repeated using the same questionnaire to evaluate the test-retest reliability. RESULTS: The ERC-Malay (ERC-M) has excellent qualitative and quantitative measurements in both item-level content validation index (I-CVI) and scale-level content validation index (S-CVI). In addition, the ERC-M demonstrated good internal consistency from Cronbach's alpha and test-retest reliability based on the Intraclass Correlation Coefficient (ICC) in all domains. CONCLUSION: ERC-M can potentially be used as a tool to evaluate emotion for the population with emotional dysregulation issue, such as autism spectrum disorder.


Assuntos
Transtorno do Espectro Autista , Regulação Emocional , Lista de Checagem , Comparação Transcultural , Humanos , Idioma , Malásia , Reprodutibilidade dos Testes , Inquéritos e Questionários
11.
Med J Malaysia ; 76(2): 205-211, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33742629

RESUMO

OBJECTIVE: This study is a preliminary work to develop a Malay version questionnaire named 'Inventori Persepsi bagi Muslim yang Memiliki Masalah Pendengaran (IPM3P)' to assess the perception on Islamic understanding and practice among Muslim adults with hearing impairment. METHODS: The scale development involved three phases: i) generation of domains based on the literature, ii) generation of sub-domains based on literature review and Islamic panel survey, and iii) generation of items. RESULTS: Preliminary version of IPM3P consists of 59 items was produced, representing three domains: Obligation (18 items), Practice (21 items), and Difficulty (20 items), and seven sub-domains ('Ibadah', 'Aqidah', 'Muamalat', 'Tasawwuf', 'Akhlak','Da'wah', and 'Sirah'). CONCLUSION: The preliminary version of IPM3P needs to be psychometrically tested. This pioneering study may become an impetus towards more research pertaining to understanding the effect of hearing loss towards religious life in the future in Malaysia.


Assuntos
Perda Auditiva , Islamismo , Adulto , Humanos , Malásia , Inquéritos e Questionários
12.
Med J Malaysia ; 74(2): 168-173, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31079129

RESUMO

INTRODUCTION: This paper describes the development and the evaluation of a new Two-dimensional (2D) computer-based (CB) Simulated Learning Environment (SLE) software for routine audiology tests that comes with learning assistance for audiology students. The aim of the study was to serve as preliminary evaluation on the effectiveness of the new 2D CB SLE audiology software among audiology students. MATERIALS AND METHODS: The development process of the new 2D CB SLE includes, (i) the identification of common errors made by students in the audiology clinic, (ii) the development of five case simulations that include four routine audiology tests incorporating learning assistance derived from the errors commonly made by audiology students and, (iii) the development of 2D CB SLE from a technical perspective. A preliminary evaluation of the use of the 2D CB SLE software was conducted among twenty-six second-year undergraduate audiology students. RESULTS: The pre-analysis evaluation of the new 2D CB SLE showed that the majority of the students perceived the new 2D CB SLE software as realistic and helpful for them in achieving the course learning outcomes and in improving their clinical skills. The mean overall scores among the twenty-six students using the self-reported questionnaire were significantly higher when using the 2D CB SLE software than with the existing software typically used in their SLE training. CONCLUSIONS: This new 2D CB SLE software has the potential for use by audiology students for enhancing their learning.


Assuntos
Audiologia/educação , Simulação por Computador , Instrução por Computador , Instrução por Computador/métodos , Avaliação Educacional , Humanos , Software
13.
Org Biomol Chem ; 16(43): 8181-8190, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30357248

RESUMO

One of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field. Cationic peptide dendrimers (PDs), as a relatively new direction, have significant advantages as gene delivery vehicles by virtue of non-natural ε-amide bonds that significantly increase their resistance to proteolysis. Moreover they also possess much lower cytotoxicity than linear peptides, which is crucial for the potential clinical application of CPs. In a further development of oligonucleotide delivery systems, we have synthesized a collection of 14 CPs, including linear peptides, lipopeptides and PDs. Their activity was evaluated by transfection of 293T cells with plasmids containing reporter genes encoding luciferase or a green fluorescent protein. The obtained results demonstrated that the greatest activity was exhibited by PDs, particularly LTP, an arginine-rich peptide dendrimer, which possesses low cytotoxic and hemolytic activity. The peptide exhibited high cell-penetrating activity, confirmed by fast dissipation of the membrane potential of cells probed by dis-C3-(5). The quantitative analysis of labelled LTP in tissue samples of mice revealed that the Cy5-LTP/siRNA complexes have a reasonable tropism to lung tissues.


Assuntos
DNA/química , DNA/genética , Dendrímeros/química , Portadores de Fármacos/química , Peptídeos/química , Transfecção , Sequência de Aminoácidos , Animais , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/farmacocinética , Peptídeos/farmacologia , Plasmídeos/genética , Distribuição Tecidual
14.
Allergy Asthma Proc ; 39(6): 430-436, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326990

RESUMO

Background: Asthma is a chronic and complex lung disease that is not completely understood. It involves airway inflammation, reversible airflow obstruction, and bronchial hyperresponsiveness. The most common symptoms are recurrent wheezing, chest tightness, shortness of breath, and coughing. Objective: The Asthma Insights and Management study gathered information on the burden of asthma in the Gulf region (United Arab Emirates, Kuwait, Saudi Arabia) and Russia. Methods: This was a cross-sectional, multinational, noninterventional, two-phase study that collected data from patients ages ≥ 12 years, through interviews and a survey questionnaire. Phase 1 consisted of survey questions focused on estimating the asthma prevalence in the community. Phase 2 was designed to assess the level of asthma control, asthma-related perceptions and behaviors, and presentation patterns. Data were summarized by using descriptive analyses. Results: Analysis of data of 711 patients revealed that the prevalence of asthma among patients who lived in the community was 7.9% and that 66% subjectively perceived their asthma as being controlled. However, 97% of the patients' asthma were partially controlled or uncontrolled based on the Global initiative for Asthma control classification. Troubling symptoms were daytime coughing (33.3%) and shortness of breath (20.3%). With respect to medications for asthma, 76.2% of the patients reported the use of quick relief medication and 80.8% of maintenance medication during the past 4 weeks. Asthma exacerbation in the past year was reported by 40% of adults and adolescents in the study. Conclusion: The results showed that a significant proportion of the patients experienced bothersome symptoms and that many had a lack of knowledge about asthma control and treatment recommendations, which indicated that there is a need for improvements in patient education and asthma care in the Gulf and Russia regions.


Assuntos
Asma/epidemiologia , Asma/diagnóstico , Asma/etiologia , Asma/terapia , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Masculino , Oriente Médio/epidemiologia , Fenótipo , Vigilância da População , Prevalência , Federação Russa/epidemiologia , Autorrelato , Fatores Socioeconômicos
15.
Bull Environ Contam Toxicol ; 98(6): 817-823, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28484803

RESUMO

Increased toxicity due to high metal concentrations may hinder the ecological integrity of aquatic ecosystems in sustaining life. The non-biodegradable nature of metals may result in bioaccumulation in aquatic organisms. Due to ecological and social aspects it is imperative for monitoring schemes to identify possible impacts to the systems integrity. This paper discusses accumulation patterns of seven metals (Al, Cr, Cu, Fe, Mn, Sr and Zn) in tissues of two fish species, namely Clarias gariepinus and Oreochromis mossambicus at two selected sites, the first located upstream of Modimolle (NRS1), and the second located downstream of the town (NRS2). Gills, liver, muscle and skin tissues were analysed for metal concentrations using standard microwave digestion and inductively coupled plasma mass spectrometry techniques. Statistical results indicated higher concentrations of metals at NRS2 in comparison to NRS1, indicating that Modimolle plays a potential role in introducing metals into the aquatic system.


Assuntos
Monitoramento Ambiental/métodos , Peixes/metabolismo , Metais/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Peixes-Gato , Ecologia , Ecossistema , Brânquias/química , Metais/análise , Análise Multivariada , Rios/química , África do Sul , Tilápia , Poluentes Químicos da Água/análise
17.
Anaesthesia ; 70(5): 549-54, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25557303

RESUMO

We investigated whether the contamination of samples with glucose subsequently tested for haemostasis affected the results, including prothrombin time, activated partial thromboplastin time and fibrinogen concentration. Venous blood was collected from 12 healthy subjects and divided into four aliquots, which were subjected to different degrees of contamination with standard glucose solution (0%, 5%, 10%, 20%). With increasing glucose contamination, prothrombin time increased from mean (SD) 11.0 (0.7) s to 11.2 (0.7) s, 11.5 (0.7) s and 12.2 (0.8) s, all p < 0.001. Activated partial thromboplastin time decreased from 32.3 (0.9) s to 30.9 (0.8) s, 30.8 (0.8) s, and 29.7 (0.7) s, all p < 0.001. Fibrinogen concentration decreased from 3.8 (0.7) g.l(-1) to 3.7 (0.6) g.l(-1), 3.6 (0.6) g.l(-1), and 3.4 (0.6) g.l(-1), all p < 0.001. Bias was clinically meaningful from 5% contamination for activated partial thromboplastin time, 10% contamination for prothrombin time and 20% contamination for fibrinogen concentration. We conclude that if glucose contamination of haemostasis samples is suspected or has occurred, the specimens should not be analysed.


Assuntos
Glicemia/análise , Testes Hematológicos , Hemostasia , Hiperglicemia/sangue , Fibrinogênio/análise , Voluntários Saudáveis , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Valores de Referência , Reprodutibilidade dos Testes
18.
ScientificWorldJournal ; 2014: 301891, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25431783

RESUMO

BACKGROUND: The best surgical technique for large liver hydatid cysts (LHCs) has not yet been agreed on. Objectives. The objective of this study was to examine the role of perioperative endoscopic retrograde cholangiopancreatography (ERCP) and biliary drainage in patients with large LHCs. MetHODS: A 20-year retrospective study of patients with LHCs treated surgically at the University Clinical Center of Kosovo (UCCK). We divided patients into 2 groups based on treatment period: 1981-1990 (Group I) and 2001-2010 (Group II). Demographic characteristics (sex, age), the surgical procedure performed, complications rate, and outcomes were compared. RESULTS: Of the 340 patients in our study, 218 (64.1%) were female with median age of 37 years (range, 17 to 81 years). 71% of patients underwent endocystectomy with partial pericystectomy and omentoplication, 8% total pericystectomy, 18% endocystectomy with capitonnage, and 3% external drainage. In Group I, 10 patients underwent bile duct exploration and T-tube placement; in Group II, 39 patients underwent bile duct exploration and T-tube placement. In addition, 9 patients in Group II underwent perioperative ERCP with papillotomy. The complication rate was 14.32% versus 6.37%, respectively (P = 0.001). CONCLUSION: Perioperative ERCP and biliary drainage significantly decreased the complication rate and improved outcomes in patients with large LHCs.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Drenagem/métodos , Equinococose Hepática/cirurgia , Assistência Perioperatória/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Equinococose Hepática/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
19.
Vaccines (Basel) ; 11(4)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37112786

RESUMO

The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4+/CD8+ T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell® thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19.

20.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 2): o266, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22346910

RESUMO

The complete molecule of the title compound, C(28)H(38)O(2), is generated by a crystallographic centre of symmetry. The molecular conformation displays an intra-molecular C-H⋯π inter-action.

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