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1.
Immunol Cell Biol ; 102(1): 21-33, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37795567

RESUMO

The human pathogen Streptococcus pyogenes, or Group A Streptococcus (GAS), is associated with a variety of diseases ranging from mild skin and soft tissue infections to invasive diseases and immune sequelae such as rheumatic heart disease. We have recently reported that one of the virulence factors of this pathogen, the pilus, has inflammatory properties and strongly stimulates the innate immune system. Here we used a range of nonpathogenic Lactococcus lactis gain-of-function mutants, each expressing one of the major pilus types of GAS, to compare the immune responses generated by various types of fully assembled pili. In vitro assays indicated variability in the inflammatory response induced by different pili, with the fibronectin-binding, collagen-binding, T antigen (FCT)-1-type pilus from GAS serotype M6/T6 inducing significantly stronger cytokine secretion than other pili. Furthermore, we established that the same trend of pili-mediated immune response could be modeled in Galleria mellonella larvae, which possess a similar innate immune system to vertebrates. Counterintuitively, across the panel of pili types examined in this study, we observed a negative correlation between the intensity of the immune response demonstrated in our experiments and the disease severity observed clinically in the GAS strains associated with each pilus type. This observation suggests that pili-mediated inflammation is more likely to promote bacterial clearance instead of causing disruptive damages that intensify pathogenesis. This also indicates that pili may not be the main contributor to the inflammatory symptoms seen in GAS diseases. Rather, the immune-potentiating properties of the pilus components could potentially be exploited as a vaccine adjuvant.


Assuntos
Fímbrias Bacterianas , Streptococcus pyogenes , Animais , Humanos , Virulência , Streptococcus pyogenes/fisiologia , Fímbrias Bacterianas/fisiologia , Pele , Proteínas de Bactérias
2.
Matern Child Nutr ; 19(1): e13426, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069350

RESUMO

We assessed the associations between women's empowerment and anaemia and haemoglobin concentration among children (6-59 months) in 31 sub-Saharan African (SSA) countries. We included 72,032 mother-child pairs from Demographic and Health Surveys conducted between 2006 and 2019. A three-dimensional women's empowerment index (attitude towards violence, decision making and social independence) was constructed using principal components analysis, and associations between the index and any anaemia and Hb concentration were assessed using multilevel regression. The mean (standard deviation) haemoglobin concentration was 102.3 (16.0 g/L) and 65.8% of the children were anaemic. The odds of anaemia reduced with increasing empowerment in the dimensions of attitude towards violence [quintile (Q5) versus Q1, OR 0.77; 95% confidence interval [CI] 0.65-0.89, ptrend = 0.006], decision making (Q5 vs. Q1, OR 0.72; 95% CI 0.61-0.84, ptrend < 0.001) and social independence (Q5 vs. Q1, OR 0.86; 95% CI 0.76-0.97, ptrend = 0.015). The mean Hb concentration increased with increasing women's empowerment in the dimensions of attitude towards violence (Q5 vs. Q1, mean difference [MD] 1.40 g/L; 95% CI 0.63-2.17, ptrend < 0.001) and social independence (Q5 vs. Q1, MD 1.32 g/L; 95% CI 0.36-2.28, ptrend = 0.001). There was no evidence for a linear trend in the association between decision making and haemoglobin concentration (ptrend = 0.051). Women's empowerment was associated with reduced odds of any anaemia and higher haemoglobin concentration in children. The promotion of women's empowerment may play a role in reducing the burden of childhood anaemia in SSA.


Assuntos
Anemia , Empoderamento , Feminino , Humanos , África Subsaariana/epidemiologia , Anemia/epidemiologia , Tomada de Decisões , Hemoglobinas , Análise Multinível
3.
Immunol Cell Biol ; 100(3): 174-185, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35124861

RESUMO

The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS virulence, the pilus has become an attractive target for vaccine development. While current research mainly focuses on pilus function and its potential as a vaccine component, there is a lack of knowledge on how the host immune system recognizes and responds to this abundant surface structure. Here we show that both assembled GAS pili and individual pilus proteins induce a potent release of the proinflammatory cytokines tumor necrosis factor and interleukin-8. We further show that the surface-exposed backbone pilin and ancillary pilin 1 subunits are Toll-like receptor 2 (TLR2) agonists. Using reporter cell lines coexpressing human TLR2 in combination with either TLR1 or TLR6, we determined that activation was mediated by the TLR2/TLR6 heterodimer. Finally, we used solid-phase and flow cytometry binding assays to illustrate a direct interaction between the pilus subunits and TLR2. These results provide further support for the suitability of the pilus as a vaccine component and opens potential avenues for using GAS pili as an adjuvant or immune-modulation agent.


Assuntos
Proteínas de Fímbrias , Streptococcus pyogenes , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Fímbrias/metabolismo , Humanos , Imunidade Inata , Streptococcus pyogenes/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 6 Toll-Like/metabolismo
4.
Clin Exp Nephrol ; 25(11): 1215-1223, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34129133

RESUMO

BACKGROUND: Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. METHODS: Study design: cohort study. SETTING: participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. PREDICTOR: patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. OUTCOMES: all-cause mortality and hospitalization during the mean 2.8-year follow-up. MEASUREMENTS: hazard ratios (HRs) were estimated using Cox's model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. RESULTS: The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. CONCLUSIONS: PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.


Assuntos
Hospitalização/estatística & dados numéricos , Mortalidade , Polimedicação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal
5.
Alcohol Alcohol ; 53(1): 121-128, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087434

RESUMO

AIMS: To assess the effectiveness of community-based alcohol brief interventions (ABI) implemented by community-health workers with and without motivational talks (MT) by former drinkers, in reducing harmful and hazardous alcohol consumption. METHODS: We conducted a three-arm quasi-experimental study (one control and two intervention groups) between May and December 2015 in Kakamega County, Kenya. Participants were hazardous or harmful alcohol drinkers with an Alcohol Use Disorders Identification Test (AUDIT) score of 8-19 at baseline. One intervention group received only ABI while the other received ABI + MT. The interventions' effects on AUDIT scores were analysed using linear mixed models. Logistic regression was used to analyse the interventions' effects on low-risk drinking (AUDIT score <8) after 6 months. RESULTS: The study included 161 participants: 52 in the control group, 52 in the only ABI group and 57 in the ABI + MT group. The mean AUDIT scores were lower in the intervention groups at 1, 3 and 6 months post-intervention; the ABI + MT group showed a greater reduction. The mean AUDIT scores over a 6-month period were lower in both intervention groups compared with the control group. The odds of low-risk drinking were almost two times higher in both intervention groups than in the control group, although the effect of only ABI on low-risk drinking was not significant. CONCLUSIONS: ABI + MT and only ABI were associated with a reduced mean AUDIT score among hazardous and high-risk drinkers in this resource-limited setting. ABI + MT was also associated with low-risk drinking in this population. SHORT SUMMARY: Community-based alcohol brief interventions implemented by community-health workers accompanied by motivational talks by former drinkers were associated with reduced hazardous and harmful alcohol consumption in a rural setting in western Kenya.


Assuntos
Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Serviços de Saúde Comunitária/estatística & dados numéricos , População Rural , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/terapia , Agentes Comunitários de Saúde , Feminino , Humanos , Quênia/epidemiologia , Modelos Logísticos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Entrevista Motivacional , Fatores Socioeconômicos , Resultado do Tratamento , Adulto Jovem
6.
BMC Psychiatry ; 17(1): 175, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28486959

RESUMO

BACKGROUND: Studies on alcohol consumption in rural areas in sub-Saharan Africa are scarce. This study aimed to determine the prevalence and determinants of alcohol consumption in rural western Kenya. The study was conducted as a preliminary stage of a community-based intervention to reduce hazardous alcohol consumption. METHODS: A cross-sectional survey of 478 participants aged 18-65 years residing in Ikolomani Sub-county, Kakamega County was conducted in April 2015. Data were collected using an interviewer-administered questionnaire. We defined current drinkers as participants who consumed any alcoholic product in the preceding one month, and hazardous/high-risk drinkers as participants with an Alcohol Use Disorders Identification Test (AUDIT) score of 8 and above. We summarised data using descriptive statistics and used logistic regression to explore for the correlates of each of current alcohol consumption and hazardous/high-risk alcohol consumption. RESULTS: The sex-standardized prevalence of current alcohol drinkers was 31.7% (95% confidence interval (CI): 26.8%-37.2%). The prevalence was higher in men (54.6%) than in women (8.9%). The mean AUDIT score among current drinkers was 16.9 (SD 8.2) and the sex-standardized prevalence of hazardous/high-risk alcohol drinking was 28.7% (95% CI: 24.1%-34.0%). Traditional brews were the most commonly consumed types of alcohol and most drinkers took alcohol in the homes of alcohol sellers/brewers. In multivariate analyses, the number of drinkers in the family, the number of friends who are drinkers and the attitude towards alcohol intake were positively associated with current alcohol drinking status, and with hazardous/high-risk alcohol consumption. Women were less likely to be current drinkers and hazardous/high-risk drinkers than were men. Other socio-demographic factors were not significantly associated with alcohol consumption. CONCLUSIONS: The prevalence of alcohol consumption in the study area was higher than the national level estimate of 13.3%. The results suggest that the social environment is the main determinant of alcohol consumption in this setting. These findings imply that interventions to mitigate alcohol consumption in this area will have to target the social networks of the alcohol consumers, change the drinkers' attitude towards alcohol, and tackle the issue of availability of unlicensed homemade brews.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , População Rural/estatística & dados numéricos , Adolescente , Adulto , Idoso , Alcoolismo/etiologia , Estudos Transversais , Feminino , Humanos , Quênia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
7.
Reprod Health ; 14(1): 65, 2017 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-28532513

RESUMO

BACKGROUND: Access to adequate antenatal care (ANC) is critical in ensuring a good maternal health and in preventing maternal and neonatal morbidity and mortality. South Sudan has one of the world's poorest health indicators due to a fragile health system and a combination of socio-cultural, economic, and political factors. This study was conducted to identify barriers to utilisation of ANC services in Rumbek North County. METHODS: Using a qualitative design, data were collected through 14 focus group discussions with 169 women and 45 men and 12 key informant interviews with community leaders, staff working in health facilities, and the staff of the County Health Department. Data were analysed using inductive content analysis. RESULTS: The perceived barriers to ANC utilisation were categorised as follows: 1) Issues related to access to health facilities and lack of resources. These included long distance to health facilities, lack of means of transportation to the health facilities, floods and poor roads, and demand for payment for health care at some health facilities; 2) The influence of the socio-cultural context and conflict including heavy burden of domestic chores, the negative influence of husbands who were reluctant to allow their wives to attend ANC, and insecurity; 3) Perceptions about pregnancy including misperceptions about the benefits of ANC and low perceived risk of pregnancy-related complications; and 4) Perceptions about the quality of care and the efficacy of medical treatment. CONCLUSIONS: This study identified a myriad of factors deeply entrenched in the society, which prevent women from utilising ANC services. It also elicits broad aspects of interconnectedness among the barriers. To ensure effectiveness, strategies to improve utilisation of ANC in the study area and in similar contexts need to take into account the barriers identified by this study.


Assuntos
Serviços de Saúde da Criança/estatística & dados numéricos , Serviços de Saúde Materna/estatística & dados numéricos , Cuidado Pré-Natal , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Pesquisa Qualitativa , Sudão do Sul
8.
Sleep Breath ; 19(1): 85-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24622960

RESUMO

PURPOSE: Sleep apnea is sometimes associated with hypothyroidism, but the significance of thyroid function screening in sleep apnea patients has been controversial. In the present study, we investigated the relationship between thyroid function and sleep apnea in subjects who were suspected to have sleep apnea. METHODS: We enrolled 156 consecutive subjects suspected of having sleep apnea. Subjects included 117 men and 39 women aged 21 to 84 years. They underwent nocturnal multichannel polysomnography during a one-night hospitalization. The examined indices of sleep apnea were apnea-hypopnea index (AHI), lowest oxygen saturation, oxygen desaturation index, longest apnea duration, mean apnea duration, and the percent of apnea time to sleep time. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were concomitantly measured by electrochemiluminescence immunoassays. RESULTS: Three subjects (1.9 %) were diagnosed with primary hypothyroidism (high TSH and low FT4), and one subject (0.6 %) with subclinical hypothyroidism (high TSH and normal FT4). No significant difference in the level of TSH, FT3, or FT4 was seen among subjects with different severity of sleep apnea. The mean apnea duration significantly correlated with TSH in both simple and multiple regression analyses. Subjects with lower FT3 (≤3.75 pg/ml) showed longer mean apnea time compared to those with higher FT3 (>3.75 pg/ml) (24.9 ± 0.8 vs. 20.2 ± 1.2 s; P = 0.009). The other indices of sleep apnea did not show significant correlation with thyroid function. CONCLUSIONS: These results suggest that the mean apnea duration and TSH/FT3 may be helpful in understanding reciprocity between the two disease states, and for evaluating the validity of thyroid function tests in patients with sleep apnea.


Assuntos
Hipotireoidismo/epidemiologia , Hipotireoidismo/fisiopatologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/diagnóstico , Japão , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Estatística como Assunto , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
9.
Reprod Health ; 12: 74, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26432298

RESUMO

BACKGROUND: Ethiopia has high maternal mortality ratio and poor access to maternal health services. Attendance of at least four antenatal care (ANC) visits and delivery by a skilled birth attendant (SBA) are important in preventing maternal deaths. Understanding the reasons behind the poor use of these services is important in designing strategies to address the problem. This study aimed to determine the coverage of at least four ANC visits and delivery by a SBA and to identify determinants of utilisation of these services in three districts in South West Shoa Zone, Ethiopia. METHODS: A cross-sectional survey of 500 women aged 15-49 years with a delivery in two years prior to the survey was conducted in Wolisso, Wonchi and Goro districts in February 2013. Data were collected using an interviewer administered questionnaire. Logistic regression models were used to explore determinants of ANC attendance and SBA at delivery. RESULTS: Coverage of at least four ANC visits and SBA at delivery were 45.5 and 28.6 %, respectively. Most institutional deliveries (69 %) occurred at the single hospital that serves the study districts. Attendance of at least four ANC visits was positively associated with wealth status, knowledge of the recommended number of ANC visits, and attitude towards maternal health care, but was negatively associated with woman's age. SBA at delivery was negatively associated with parity and time to the health facility, but was positively associated with urban residence, wealth, knowledge of the recommended number of ANC visits, perceived good quality of maternal health services, experience of a pregnancy/delivery related problem, involvement of the partner/family in decision making on delivery place, and birth preparedness. CONCLUSIONS: Raising awareness about the minimum recommended number of ANC visits, tackling geographical inaccessibility, improving the quality of care, encouraging pregnant women to have a birth and complication readiness plan and community mobilisation targeting women, husbands, and families for their involvement in maternal health care have the potential to increase use of maternal health services in this setting. Furthermore, supporting health centres to increase uptake of institutional delivery services may rapidly increase coverage of delivery by SBA and reduce inequity.


Assuntos
Parto Obstétrico/estatística & dados numéricos , Serviços de Saúde Materna/estatística & dados numéricos , Cuidado Pré-Natal/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Etiópia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Modelos Logísticos , Mortalidade Materna , Pessoa de Meia-Idade , Tocologia , Razão de Chances , Fatores Socioeconômicos
10.
BMC Pregnancy Childbirth ; 14: 259, 2014 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-25091866

RESUMO

BACKGROUND: Skilled attendance at delivery is critical in prevention of maternal deaths. However, many women in low- and middle-income countries still deliver without skilled assistance. This study was carried out to identify perceived barriers to utilisation of institutional delivery in two districts in Karamoja, Uganda. METHODS: Data were collected through participatory rural appraisal (PRA) with 887 participants (459 women and 428 men) in 20 villages in Moroto and Napak districts. Data were analysed using deductive content analysis. Notes taken during PRA session were edited, triangulated and coded according to recurring issues. Additionally, participants used matrix ranking to express their perceived relative significance of the barriers identified. RESULTS: The main barriers to utilisation of maternal health services were perceived to be: insecurity, poverty, socio-cultural factors, long distances to health facilities, lack of food at home and at health facilities, lack of supplies, drugs and basic infrastructure at health facilities, poor quality of care at health facilities, lack of participation in planning for health services and the ready availability of traditional birth attendants (TBAs). Factors related to economic and physical inaccessibility and lack of infrastructure, drugs and supplies at health facilities were highly ranked barriers to utilisation of institutional delivery. CONCLUSION: A comprehensive approach to increasing the utilisation of maternal health care services in Karamoja is needed. This should tackle both demand and supply side barriers using a multi-sectorial approach since the main barriers are outside the scope of the health sector. TBAs are still active in Karamoja and their role and influence on maternal health in this region cannot be ignored. A model for collaboration between skilled health workers and TBAs in order to increase institutional deliveries is needed.


Assuntos
Parto Obstétrico/estatística & dados numéricos , Países em Desenvolvimento , Instalações de Saúde/estatística & dados numéricos , Serviços de Saúde Rural/estatística & dados numéricos , Atitude do Pessoal de Saúde , Cultura , Parto Obstétrico/economia , Feminino , Abastecimento de Alimentos , Instalações de Saúde/economia , Recursos em Saúde/provisão & distribuição , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Participação do Paciente , Pobreza , Pesquisa Qualitativa , Serviços de Saúde Rural/economia , Uganda
11.
Microorganisms ; 12(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543606

RESUMO

The Gram-positive human pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) employs an arsenal of virulence factors that contribute to its pathogenesis. The pilus is an important factor that enables the pathogen to adhere to and colonize host tissues. Emerging research in pilus function shows that pili's involvement in establishing infection extends beyond host adhesion. The diversity of GAS pilus types reflect the varying characteristics identified in different pili. With the development of new experimental systems and animal models, a wider range of biological functions have been explored. This brief review summarizes recent reports of new functions in different GAS pilus types and the methodologies that contributed to the findings. The established importance of the pilus in GAS pathogenesis makes this surface structure a promising vaccine target. This article also reviews recent advancements in pilus-based vaccine strategies and discusses certain aspects that should be considered in vaccine development according to the newly defined properties of pili.

12.
Nihon Jibiinkoka Gakkai Kaiho ; 116(7): 789-92, 2013 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-23980484

RESUMO

Obstructive sleep apnea syndrome (OSAS) is thought to be closely related to nasal airway resistance, which accounts for approximately one half of total upper airway resistance. This retrospective study aimed at elucidating the effect of endoscopic endonasal surgery on OSAS. Nine consecutive patients with OSAS complaining of nasal obstruction who underwent endoscopic endonasal surgery were enrolled. They were 8 men and 1 woman ranging from 34-73 years of age with an average of 53.2 years. All patients had chronic hypertrophic rhinitis and nasal septal deviation, and underwent septoplasty and submucous turbinectomy. The severity of OSAS was assessed by 8 sleep apnea indices of polysomnography before and after surgery. The indices included the apnea-hypopnea index (AHI), maximum apnea time, mean apnea time, minimum blood oxygen saturation, mean blood oxygen saturation, blood oxygen saturation decline index, awakening response index, and ratio of snoring time to sleep time. Significant decrease in the AHI (27.6 +/- 5.3 vs. 20.7 +/- 5.5/hr; p = 0.033), in the awakening response index (30.5 +/- 3.3 vs. 21.2 +/- 5.3/hr; p = 0.028), and increase in the mean blood oxygen saturation (95.1 +/- 0.7 vs. 96.0 +/- 0.7%; p = 0.023) were observed postoperatively. There was no significant change in the other 5 indices. In addition, nasal airflow resistance measured by acoustic rhinometry had significantly reduced during the periods of both inhalation (474.4 +/- 49.0 vs. 842.7 +/- 50.2cm3/s; p = 0.002) and exhalation (467.3 +/- 57.3 vs. 866.0 +/- 80.6 cm3/s; p = 0.004). The pre- and postoperative body mass indices did not differ statistically from each other. These results indicate that endoscopic endonasal surgery alone has a potential effect on sleep-disordered breathing in OSAS patients with nasal obstruction. We should be aware of such a positive impact of endonasal surgery upon the management of OSAS.


Assuntos
Septo Nasal/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Conchas Nasais/cirurgia , Adulto , Idoso , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
14.
Yakugaku Zasshi ; 140(12): 1477-1483, 2020 Dec 01.
Artigo em Japonês | MEDLINE | ID: mdl-32921648

RESUMO

Asthma and chronic obstructive pulmonary disease (COPD) are characterised by chronic inflammation in the lung that is associated with airway obstruction. Inhaled therapy with a combination of corticosteroid and a long-acting ß2-agonist is an effective anti-inflammatory medicine for asthma, but in patients with severe asthma and COPD fails to completely control these symptoms with current therapies. The inflammatory process in these diseases, which involves activation of the coagulation and fibrinolytic system in the lung, offers the opportunity for alternative anti-inflammatory therapies. In this study, we investigated the effects of anti-coagulants on lipopolysaccharide (LPS)-induced airway inflammation in mice. A/J mice were exposed to LPS, a bacterial endotoxin, intranasally and accumulation of inflammatory cells, TNF-α, C-X-C motif chemokine (CXCL) 1, and osteopontin in bronchoalveolar lavage fluid (BALF) was monitored by flow cytometry and an enzyme-linked immunosorbent assay. LPS exposure induced airway neutrophilia and accumulation of TNF-α, CXCL1, and osteopontin in BALF. This LPS-induced airway inflammation was not relieved using a corticosteroid, fluticasone propionate (FP), or a direct inhibitor of Factor Xa, rivaroxaban. In contrast, a direct thrombin inhibitor, dabigatran, inhibited LPS-induced airway neutrophilia and decreased inflammatory cytokine production in a dose dependent manner. Furthermore, combination of dabigatran and FP elicited stronger inhibition of LPS-induced airway inflammation. Therefore, these results suggest that dabigatran could be an effective new therapy for severe respiratory diseases.


Assuntos
Antitrombinas/uso terapêutico , Asma/tratamento farmacológico , Dabigatrana/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Antitrombinas/farmacologia , Asma/induzido quimicamente , Asma/diagnóstico , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Quimiocina CXCL1/análise , Dabigatrana/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Fluticasona/uso terapêutico , Inflamação , Mediadores da Inflamação/análise , Masculino , Camundongos Endogâmicos , Osteopontina/análise , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fator de Necrose Tumoral alfa/análise
15.
Nutrients ; 12(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086501

RESUMO

BACKGROUND: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. METHODS: This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45-59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox's regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. RESULTS: Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox's regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. CONCLUSION: Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.


Assuntos
Composição Corporal , Líquidos Corporais/metabolismo , Avaliação Nutricional , Diálise Renal/efeitos adversos , Zinco/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Zinco/deficiência
16.
Mol Cancer Res ; 18(4): 632-643, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31974290

RESUMO

The signaling lymphocytic activation molecule family 3 (SLAMF3) is a member of the immunoglobulin superfamily expressed on T, B, and natural killer cells and modulates the activation and cytotoxicity of these cells. SLAMF3 is also expressed on plasma cells from patients with multiple myeloma (MM), although its role in MM pathogenesis remains unclear. This study found that SLAMF3 is highly and constitutively expressed on MM cells regardless of disease stage and that SLAMF3 knockdown/knockout suppresses proliferative potential and increases drug-induced apoptosis with decreased levels of phosphorylated ERK protein in MM cells. SLAMF3-overexpressing MM cells promote aggressive myeloma behavior in comparison with cytoplasmic domain-truncated SLAMF3 (ΔSLAMF3) cells. SLAMF3 interacts directly with adaptor proteins SH2 domain-containing phosphatase 2 (SHP2) and growth factor receptor bound 2 (GRB2), which also interact with each other. SLAMF3 knockdown, knockout, ΔSLAMF3, and SHP2 inhibitor-treated MM cells decreased phosphorylated ERK protein levels. Finally, serum soluble SLAMF3 (sSLAMF3) levels were markedly increased in advanced MM. Patients with high levels of sSLAMF3 progressed to the advanced stage significantly more often and had shorter progression-free survival times than those with low levels. This study revealed that SLAMF3 molecules consistently expressed on MM cells transmit MAPK/ERK signals mediated via the complex of SHP2 and GRB2 by self-ligand interaction between MM cells and induce a high malignant potential in MM. Furthermore, high levels of serum sSLAMF3 may reflect MM disease progression and be a useful prognostic factor. IMPLICATIONS: SLAMF3 may be a new therapeutic target for immunotherapy and novel agents such as small-molecule inhibitors.


Assuntos
Sistema de Sinalização das MAP Quinases , Mieloma Múltiplo/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Fenótipo , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Transfecção
17.
PLoS One ; 14(3): e0213763, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893364

RESUMO

INTRODUCTION: Patients with chronic kidney disease (CKD) depend on advice from healthcare professionals to avoid using unsuitable over-the-counter (OTC) drugs. Recently, qualified, registered nonpharmacist salespersons became licensed to sell OTC drugs in Japan. However, registered salespersons' knowledge and awareness of precautions regarding unsuitable OTC drugs for use in patients with CKD are unclear. OBJECTIVES: This study aimed to clarify the awareness, knowledge, and implementation of precautions by registered salespersons regarding OTC drugs used by patients with CKD. Additionally, we evaluated the change of registered salespersons' knowledge and awareness of this topic generated by a pharmacist intervention. METHODS: A questionnaire survey and pharmacist intervention were applied to 175 registered salespersons. The intervention comprised a 50-minute lecture imparted by a pharmacist who was trained in nephrology. The knowledge, awareness, and implementation of precautions by participants with respect to nonsteroidal anti-inflammatory drugs (NSAIDs) and antacids were evaluated before and after the intervention. RESULTS: Approximately half of the registered salespersons reported previous experience with selling OTC drugs that were inappropriate for patients with CKD (NSAIDs, 48.0%; antacids, 39.7%). Few participants recognized the need to check renal function when selling those drugs to such patients (NSAIDs, 25.7%; antacids, 47.5%). The registered salespersons' awareness and knowledge were significantly higher after the intervention than before it. CONCLUSION: The results indicate that before the intervention, the registered salespersons had low levels of awareness and knowledge regarding OTC drug use in patients with CKD despite having prior experience selling unsuitable OTC drugs. However, the pharmacist intervention improved the registered salespersons' awareness and knowledge. The educational program for registered salespersons might be necessary to prevent inappropriate OTC drug use by patients with CKD.


Assuntos
Conscientização , Pessoal de Saúde/psicologia , Conhecimento , Medicamentos sem Prescrição/efeitos adversos , Insuficiência Renal Crônica/etiologia , Adulto , Antiácidos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Inquéritos e Questionários
18.
PLoS One ; 12(11): e0185726, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29095824

RESUMO

Effective from May 2014, community-based traditional birth attendants (TBAs) in Yirol West County, South Sudan, were directed to start referring all women in labour to health facilities for childbirth instead of assisting them in the villages. This study aimed to understand the degree of integration of TBAs in the health system, to reveal the factors influencing the integration, and to explore the perceived solutions to the challenges faced by TBAs. A qualitative study utilising 11 focus group discussions with TBAs, 6 focus group discussions with women, and 18 key informant interviews with members of village health committees, staff of health facilities, and staff of the County Health Department was conducted. Data were analysed using qualitative content analysis. The study found that many TBAs were referring women to health facilities for delivery, but some were still attending to deliveries at home. Facilitators of the adoption of the new role by TBAs were: acceptance of the new TBAs' role by the community, women and TBAs, perceptions about institutional childbirth and risks of home childbirth, personal commitment and motivation by some TBAs, a good working relationship between community-based TBAs and health facility staff, availability of incentives for women at health facilities, and training of TBAs. Challenges of integrating TBAs in the health system included, among others, communication problems between TBAs and health care facilities, delays in seeking care by women, insecurity, lack of materials and supplies for TBAs, health system constraints, insufficient incentives for TBAs, long distances to health facilities and transportation problems. This study has revealed encouraging developments in TBAs' integration in the formal health system in Yirol West. However, there is need to address the challenges faced by TBAs in assuming their new role in order to sustain the integration.


Assuntos
Parto Obstétrico , Parto Domiciliar , Tocologia , Adolescente , Adulto , Feminino , Grupos Focais , Humanos , Gravidez , Sudão , Adulto Jovem
19.
PLoS One ; 11(12): e0168083, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27977745

RESUMO

BACKGROUND: South Sudan has one of the world's poorest health indicators due to a fragile health system and a combination of socio-cultural, economic and political factors. This study was conducted to identify barriers to utilisation of institutional childbirth services in Rumbek North County. METHODS: Data were collected through 14 focus group discussions with 169 women and 45 men, and 18 key informant interviews with community leaders, staff working in health facilities, traditional birth attendants, and the staff of the County Health Department. Data were analysed using inductive content analysis. RESULTS: The barriers to institutional childbirth were categorised under four main themes: 1) Issues related to access and lack of resources: long distance to health facilities, lack of transportation means, referral problems, flooding and poor roads, and payments in health facilities; 2) Issues related to the socio-cultural context and conflict: insecurity, influence of the husband, lack of birth preparedness, domestic chores of women, influence of culture; 3) Perceptions about pregnancy and childbirth: perceived benefit of institutional childbirth, low childbirth risk perception, and medicalisation of childbirth including birth being perceived to be natural, undesirable birth practices, privacy concerns, and fear of caesarean section; and 4) Perceptions about the quality of care: inadequate health facility infrastructure and perceived neglect during admission. CONCLUSIONS: Multiple factors hinder institutional childbirth in Rumbek North. Some of the factors such as insecurity and poor roads are outside the scope of the health sector and will require a multi-sectoral approach if childbirth services are to be made accessible to women. Detailed recommendations to increase utilisation of childbirth services in the county have been suggested.


Assuntos
Parto Obstétrico/estatística & dados numéricos , Instalações de Saúde/estatística & dados numéricos , Adulto , Feminino , Instalações de Saúde/economia , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Gravidez , Fatores Socioeconômicos , Sudão do Sul , Recursos Humanos , Adulto Jovem
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