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INTRODUCTION: The World Health Organisation has implemented multiple HIV prevention policies and strived to achieve the 90-90-90 goal by 2020, achieving the 95-95-95 goal by 2030, which refers to 95% of patients living with HIV knowing their HIV status, 95% of patients living with HIV receiving continual care and medication, and 95% of patients living with HIV exhibiting viral suppression. However, how to measure the status of viral suppression varies, and it is hard to indicate the quality of HIV care. The study aimed to examine the long-term viral load suppression in these cases and explore potential factors affecting the control of long-term viral load. METHODS: This study analyzed viral load testing data from HIV patients who are still alive during the period from notification up to 2019-2020. Three indicators were calculated, including durable viral suppression, Viremia copy-years, and Viral load > 1,500 copies/ml, to assess the differences between them. RESULTS: Among the 27,706 cases included in the study, the proportion of persistent viral load suppression was 87%, with 4% having viral loads exceeding 1,500 copies/ml. The average duration from notification to viral load suppression was 154 days, and the geometric mean of annual viral replication was 90 copies*years/ml. Regarding the last available viral load measurement, 96% of cases had an undetectable viral load. However, we observed that 9.3% of cases, while having an undetectable viral load for their last measurement, did not show consistent long-term viral load suppression. An analysis of factors associated with non-persistent viral load suppression revealed higher risk in younger age groups, individuals with an educational level of high school or below, injection drug users, cases from the eastern region, those seeking care at regional hospitals, cases with drug resistance data, individuals with lower healthcare continuity, and those with an initial CD4 count below 350 during the study period. CONCLUSIONS: The recommendation is to combine it with the indicator of sustained viral load suppression for a more accurate assessment of the risk of HIV transmission within the infected community.
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Infecções por HIV , Carga Viral , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Masculino , Feminino , Adulto , Taiwan/epidemiologia , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Adulto Jovem , Idoso , Adolescente , HIV-1/efeitos dos fármacos , Resposta Viral SustentadaRESUMO
INTRODUCTION: The government-funded pre-exposure prophylaxis (PrEP) programme was targeted to those aged under 30 years or serodiscordant couples and implemented in September 2018-October 2020 in Taiwan. The study aimed to examine the effectiveness of the programme and the relationship between sexually transmitted disease (STD) and HIV seroconversion. METHODS: This study was a retrospective cohort analysis with questionnaires designed for participants who joined the aforementioned programme in the PrEP-designated hospitals. The questionnaires included sociodemographic factors, sexual risk behaviours, number and types of sexual partners, and usage of narcotics filled in at the beginning of the programme and every 3 months. The McNemar test was used for the paired questionnaire analysis. The HIV seroconversion status among STD-notified patients nationwide was confirmed by using the data linkage method, followed up until October 2021 with stratification of PrEP programme participation or not. RESULTS: The programme recruited 2155 people. 11 participants (0.5%) had seroconversion within the programme, while 26 (1.2%) had seroconversion after withdrawing from the programme. Overall, 1892 subjects with repeated questionnaires were included in the analysis for behaviour changes with median follow-up of 289 days. After joining the programme, 94.7% of them claimed that they had sexual behaviours: the rate of those who had condomless sex rose to 5.5% (p<0.001) and the rate of those who used narcotics decreased to 2% (p<0.001), compared with their response in the pre-questionnaire. Notably, the frequency of non-use of narcotics in recent 3 months increased from 16.9% to 38.4% in the pre-questionnaire and post-questionnaire responses, among the 177 who had claimed narcotics usage in recent 12 months (p=0.003). More HIV seroconversion was found among patients with STD who did not join the programme than those who joined the programme (8.7% vs 4.9%, p=0.031). CONCLUSIONS: The government-funded programme showed HIV case reduction and positive changes in health behaviours except for condomless sex which had increased prevalence. The reduction of HIV cases was also observed among people with STD. More resources should be allocated to the PrEP programme.
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Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Masculino , Taiwan/epidemiologia , Profilaxia Pré-Exposição/métodos , Adulto , Estudos Retrospectivos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Comportamento Sexual , Inquéritos e Questionários , Parceiros Sexuais , Adulto Jovem , Financiamento Governamental , Assunção de Riscos , Soroconversão , Pessoa de Meia-Idade , Programas GovernamentaisRESUMO
Previous studies indicate that estrogen positively regulates lung cancer progression. Understanding the reasons will be beneficial for treating women with lung cancer in the future. In this study, we found that tumor formation was more significant in female EGFRL858R mice than in male mice. P53 expression levels were downregulated in the estradiol (E2)-treated lung cancer cells, female mice with EGFRL858R-induced lung cancer mice, and premenopausal women with lung cancer. E2 increased DNA methyltransferase 1 (DNMT1) expression to enhance methylation in the TP53 promoter, which led to the downregulation of p53. Overexpression of GFP-p53 decreased DNMT1 expression in lung cancer cells. TP53 knockout in mice with EGFRL858R-induced lung cancer not only changed gene expression in cancer cells but also increased the polarization of M2 macrophages by increasing C-C motif chemokine ligand 5 (CCL5) expression and decreasing growth differentiation factor 15 (GDF15) expression. The TP53 mutation rate was increased in females with late-stage but not early-stage lung cancer compared to males with lung cancer. In conclusion, E2-induced DNMT1 and p53 expression were negatively regulated each other in females with lung cancer, which not only affected cancer cells but also modulated the tumor-associated microenvironment, ultimately leading to a poor prognosis.
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In Taiwan, 14,308 locally acquired COVID-19 cases among customers and employees in Sexy Tea shops were the first cases from May 9-August 28, 2021 (weeks 19-34). Nine weeks after the community spread of COVID-19 began, the proportion of people living with HIV (PLHIV) among the COVID-19 patients peaked at 35.7%, affecting 192 HIV patients, while the prevalence of HIV infection was 0.15%. In addition to a nationwide Level 3 epidemic alert, the Taiwan Centers for Disease Control (Taiwan CDC) launched four strategies to contain this outbreak among PLHIV in this prevaccine era, including improving the quality of contact tracing, delivering health information via peer navigators, expanding SARS-CoV-2 screening and encouraging vaccination, and addressing hesitancy. The outbreak of COVID-19 related to Alpha strain among PLHIV in 2021 ceased four weeks after peaking and lasted eight weeks.
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COVID-19 , Infecções por HIV , COVID-19/epidemiologia , Surtos de Doenças/prevenção & controle , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , SARS-CoV-2 , Taiwan/epidemiologia , CháRESUMO
INTRODUCTION: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure (IOP) are likely to play a role in the pathogenesis of optic neuropathy. The potential similarities between Alzheimer's disease (AD) and NTG in cellular apoptosis leading to neurodegeneration have been shown in recent studies. Heat Shock Protein family A member 5 (HSPA5) promoter polymorphisms have been reported to be associated with a risk of AD. The purpose of our study was to investigate the role of HSPA5 promoter polymorphisms in NTG patients. METHODS: A total of 222 patients with NTG, along with 236 normal controls were enrolled in this study. Genomic DNA was amplified through a polymerase chain reaction (PCR) and identified for the polymorphic HSPA5 (-415 and -370) by Xmn1 and BstY1 restriction digestion, respectively. PCR fragments with potential polymorphic HSPA5 (-180) were subjected to sequence-analyses by a Hex-labeled primer. Genotypes for both NTG patients and control groups were compared for statistically significant differences. RESULTS: Polymorphisms (-415) G/A and (-180) del/G were completely linked in our population. The genotype and allele frequency distribution at the -415 G/A and -180 del/G sites showed a significant difference between the NTG cases and controls. The genotype frequency of HSPA5 (-415) AA/(-180) GG and the allele frequency of HSPA5 (-415) A/(-180) G were significantly lower (p = 0.04 and p = 0.01, respectively) in the NTG patients when compared with those in the control group. There was no significant difference in genotype or allele frequency distribution of the HSPA5 (-370) C/T between the NTG and control groups. There was a reduced risk of NTG associated with the carriers for the HSPA5 (-415) A/(-180) G allele compared with that in the control population (p = 0.01). CONCLUSION: HSPA5 (-415) A and (-180) G allele polymorphisms may be protective factors in the development of NTG.
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Chaperona BiP do Retículo Endoplasmático , Glaucoma , Glaucoma de Baixa Tensão , Chaperona BiP do Retículo Endoplasmático/genética , Frequência do Gene , Genótipo , Glaucoma/genética , Humanos , Pressão Intraocular , Glaucoma de Baixa Tensão/genética , Polimorfismo Genético , Regiões Promotoras GenéticasRESUMO
INTRODUCTION: Being aware of one's HIV-positive status can help reduce unprotected sex and promote early treatment seeking. Therefore, HIV self-test (HIVST) programs may help control the HIV epidemic by case finding. The aims of this study were to determine the effect of HIVST programs on HIV case finding, time to confirmatory diagnosis and factors associated with linkage to confirmatory diagnosis in Taiwan. METHODS: The Centers for Disease Control in Taiwan initiated HIVST programs and imported 78,000 self-test kits in 2017 and 2019. Clients paid 7 US dollars for a self-test kit at facilities, vending machines or online. The programs set up an HIVST logistics management system; each kit had a unique barcode for monitoring the programs because purchases were anonymous. When clients provided their test results with photo barcodes online or at HIV/AIDS-designated hospitals, they received full monetary reimbursement. We conducted a quasi-experimental interrupted time-series (ITS) analysis that covered a period of 60 months from 2015 to 2019. We enrolled a retrospective cohort of reported HIV cases with initial positive results from HIVST programs between March 2017 and July 2020. RESULTS: The ITS analysis included data from 10,976 reported HIV cases from 2015 to 2019. The HIVST-positive cohort included 386 reported HIV cases, of whom 99.7% were males and 97% were men who have sex with men (MSM); the median age was 28 years. The ITS analysis showed a positive slope change in the number of reported HIV cases immediately in the beginning implementation month (coefficient: 51.09 in 2017 and 3.62 in 2019), but there was a significant decrease over time. It was a negative slope change by 9.52 cases per month in 2017 and 5.56 cases per month in 2019. In the HIVST-positive cohort, three of five individuals linked to HIV confirmatory diagnosis within 1 month after a positive self-test result, and an early linkage to confirmatory diagnosis was associated with HIVST disclosure (adjusted OR = 6.5; 95% CI: 3.9-10.6). CONCLUSIONS: HIVST programs were associated with an increase in HIV case finding. Our findings suggest that countries with a high incidence of HIV among MSM populations should offer multichannel HIVST services.
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Infecções por HIV , Minorias Sexuais e de Gênero , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Estudos Retrospectivos , Autoteste , Taiwan/epidemiologiaRESUMO
BACKGROUND: Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progression. According to previous studies, Sp1 can interact with the estrogen receptor (ER) to coregulate gene expression. The role of interaction between Sp1 and ER in lung cancer progression is still unknown and will be clarified in this study. METHODS: The clinical relevance between Sp1 levels and survival rates in young women with lung cancer was studied by immunohistochemistry. We validated the sex dependence of lung cancer progression in EGFRL858R-induced lung cancer mice. Wound healing assays, chamber assays and sphere formation assays in A549 cells, Taxol-induced drug-resistant A549 (A549-T24) and estradiol (E2)-treated A549 (E2-A549) cells were performed to investigate the roles of Taxol and E2 in lung cancer progression. Luciferase reporter assays, immunoblot and q-PCR were performed to evaluate the interaction between Sp1, microRNAs and CD44. Tail vein-injected xenograft experiments were performed to study lung metastasis. Samples obtained from lung cancer patients were used to study the mRNA level of CD44 by q-PCR and the protein levels of Sp1 and CD44 by immunoblot and immunohistochemistry. RESULTS: In this study, we found that Sp1 expression was decreased in premenopausal women with late-stage lung cancer, resulting in a poor prognosis. Tumor formation was more substantial in female EGFRL858R mice than in male mice and ovariectomized female mice, indicating that E2 might be involved in the poor prognosis of lung cancer. We herein report that Sp1 negatively regulates metastasis and cancer stemness in E2-A549 and A549-T24 cells. Furthermore, E2 increases the mRNA and protein levels of RING finger protein 4 (RNF4), which is the E3-ligase of Sp1, and thereby decreases Sp1 levels by promoting Sp1 degradation. Sp1 can be recruited to the promoter of miR-3194-5p, and positively regulate its expression. Furthermore, there was a strong inverse correlation between Sp1 and CD44 levels in clinical lung cancer specimens. Sp1 inhibited CD44 expression by increasing the expression of miR-3194-5p, miR-218-5p, miR-193-5p, miR-182-5p and miR-135-5p, ultimately resulting in lung cancer malignancy. CONCLUSION: Premenopausal women with lung cancer and decreased Sp1 levels have a poor prognosis. E2 increases RNF4 expression to repress Sp1 levels in premenopausal women with lung cancer, thus decreasing the expression of several miRNAs that can target CD44 and ultimately leading to cancer malignancy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Estradiol/farmacologia , Feminino , Humanos , Receptores de Hialuronatos/genética , Neoplasias Pulmonares/genética , Masculino , Camundongos , MicroRNAs/genética , Proteínas Nucleares , Fator de Transcrição Sp1/genética , Fatores de TranscriçãoRESUMO
We report a case of a heart transplant recipient who presented with a rapidly growing Epstein-Barr virus (EBV)-positive, diffuse large B-cell lymphoma 7 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Because of the atypical radiologic presentation, the initial tentative diagnosis was a mediastinal abscess. This observation indicates a potential risk of EBV reactivation after coronavirus disease 2019 (COVID-19) vaccination, which might lead to or aggravate the presentation of posttransplant lymphoproliferative disorder in transplantation patients. Transplant surgeons should be aware of the potential immunomodulatory effects of the COVID-19 vaccination.
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COVID-19 , ChAdOx1 nCoV-19 , Infecções por Vírus Epstein-Barr , Transplante de Coração , Transtornos Linfoproliferativos , Humanos , ChAdOx1 nCoV-19/efeitos adversos , COVID-19/prevenção & controle , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnósticoRESUMO
In long-term care facilities (LTCFs), nurses are key healthcare providers for older residents who have depressive symptoms or depression; therefore, they need accurate knowledge of late-life depression, positive attitudes towards depression, and confidence in providing depression care. This cluster-randomized trial was designed to examine the effectiveness of multiple, face-to-face, brief training sessions in improving nurses' knowledge, attitudes, and confidence in providing late-life depression care in LTCFs. Nine LTCFs were included in the study. In total, 30 nurses from the four LTCFs assigned to the intervention group received three 30-min training sessions and 36 nurses in the five comparison group LTCFs did not. A self-report questionnaire was administered before and after the intervention. There were significant differences between groups concerning improvement in nurses' knowledge of late-life depression, attitudes towards depression, and confidence in providing depression care. The effect size (Cohen's d) was 1.55 for knowledge, 1.38 for attitudes, and 0.89 for confidence. This training program was effective in improving LTCF nurses' knowledge, attitudes, and confidence in providing depression care. On the basis of these findings, we recommend that nurse managers and directors implement similar training programs for nurses in LTCFs to enhance the care quality for older residents.
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Atitude do Pessoal de Saúde , Transtorno Depressivo/enfermagem , Enfermagem Geriátrica/educação , Conhecimentos, Atitudes e Prática em Saúde , Assistência de Longa Duração/psicologia , Recursos Humanos de Enfermagem/educação , Recursos Humanos de Enfermagem/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Inquéritos e QuestionáriosAssuntos
Isoniazida , Tuberculose Latente , Idoso , Antituberculosos , Humanos , Rifampina/análogos & derivadosRESUMO
BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.
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Inibidores da Angiogênese/efeitos adversos , Neovascularização de Coroide/tratamento farmacológico , Neuropatia Óptica Isquêmica/induzido quimicamente , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/diagnóstico , Bases de Dados Factuais , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Neuropatia Óptica Isquêmica/diagnóstico , Retratamento , Estudos Retrospectivos , Fatores de Risco , Taiwan , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnósticoRESUMO
Hot-water immersion (HWI) is a type of thermal therapy for treating various diseases. In our study, the physiological responses to occasional and regular HWI have been explored. The rats were divided into a control group, occasional group (1D), and regular group (7D). The 1D and 7D groups received 42°C during 15mins HWI for 1 and 7 days, respectively. The blood samples were collected for proinflammatory cytokines examinations, the heart, liver and kidney were excised for subsequent IHC analysis to measure the level of heat shock protein 70 (HSP70). The results revealed that the body temperature increased significantly during HWI on Day 3 and significantly declined on Days 6 and 7. For the 7D group, body weight, heart rate, hematocrit, platelet, osmolarity, and lactate level were lower than those in the 1D group. Furthermore, the levels of granulocyte counts, tumor necrosis factor-α, and interleukin-6 were lower in the 7D group than in the 1D group. The induction of HSP70 in the 1D group was higher than in the other groups. Physiological responses to occasional HWI are disadvantageous because of heat stress. However, adaptation to heat from regular HWI resulted in decreased proinflammatory responses and physical heat stress.
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Proteínas de Choque Térmico HSP70/análise , Resposta ao Choque Térmico , Hipertermia Induzida , Termotolerância , Animais , Banhos/métodos , Pressão Sanguínea , Temperatura Corporal , Citocinas/sangue , Frequência Cardíaca , Hematócrito , Hipertermia Induzida/métodos , Inflamação/sangue , Ácido Láctico/sangue , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Ratos , Ratos Endogâmicos WKYRESUMO
BACKGROUND: Saffold cardiovirus (SAFV) belongs to the Cardiovirus genus of Picornaviridae family, and may be a relevant new human pathogen; Thus far, eleven genotypes have been identified. The SAFV type 3 (SAFV-3) is thought to be the major genotype and is detected relatively frequently in children with acute gastroenteritis and respiratory illness. The epidemiology and pathogenicity of SAFV-3 remain unclear. OBJECTIVES: To investigate the genomic and epidemiologic profiles of SAFV-3 infection in Taiwan. STUDY DESIGN: Virus was detected in respiratory samples from children suffering for URI. SAFV-3 isolates were detected by isolation on cell culture and IF assay. The molecular typing was performed by RT-PCR and was sequenced to compare with reference strains available in the NCBI GeneBank. Serum samples were collected from 2005 to 2013 in Taiwan for seroprevalence investigation. RESULTS: A total of 226 specimens collected from children with URIs, 22 (9.73%) were positive for SAFV-3. The majority of SAFV-3 infections were found in children less than 6 years of age (14 of 22, 63.6%). Genetic analysis of VP1 coding region of Taiwanese isolates shown an 83.2-97.7% difference from other available SAFV-3 sequences in NCBI GenBank. Phylogenetic analysis revealed there is three genetic groups of SAFV-3 co-circulated in Taiwan during the study period. In addition, seroprevalence investigation results indicated that SAFV-3 infection occurs early in life and 43.7-77.8% of children aged between 6 months to 9 years old, had neutralizing antibodies against SAFV-3. CONCLUSION: SAFV-3 may have circulated in Taiwan for some time and it appears to be one of the etiological agents responsible for URIs in children.
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Infecções por Cardiovirus/epidemiologia , Infecções por Cardiovirus/virologia , Cardiovirus/genética , Genótipo , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Adolescente , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Cardiovirus/classificação , Cardiovirus/imunologia , Cardiovirus/isolamento & purificação , Infecções por Cardiovirus/diagnóstico , Linhagem Celular , Criança , Pré-Escolar , Feminino , Variação Genética , Genoma Viral , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Prevalência , Infecções Respiratórias/diagnóstico , Estudos Soroepidemiológicos , Taiwan/epidemiologiaRESUMO
Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances in both humans and animals. Blockade of N-methyl-d-aspartate (NMDA) receptors has been suggested to play a critical role in acute toluene-induced behavioral manifestations. Activation of type 5 metabotropic glutamate receptors (mGluR5) attenuates behavioral responses induced by NMDA receptor blockade. The present study elucidated the role of mGluR5 on toluene-induced behavioral and hypothermic responses. Male Sprague-Dawley rats received the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) or antagonist 6-methyl-2-[phenylethynyl]-pyridine (MPEP) prior to toluene administration. Rotarod test, step-down inhibitory avoidance learning task, and rectal temperature were monitored. Pretreatment of CHPG and MPEP attenuated and potentiated these toluene-induced responses, respectively. In addition, the inhibitory effects of CHPG on toluene-induced motor incoordination, learning impairment, and hypothermia were reversed by the protein kinase C (PKC) inhibitor chelerythrine chloride. These findings suggest that mGluR5 may modulate the neural circuits responsible for motor incoordination, learning impairment, and hypothermic action of toluene through a PKC-dependent signal transduction pathway.
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Comportamento Animal , Hipotermia/induzido quimicamente , Receptores de Glutamato Metabotrópico/fisiologia , Tolueno/toxicidade , Animais , Hipotermia/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptor de Glutamato Metabotrópico 5 , Teste de Desempenho do Rota-RodRESUMO
Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist. By inhibiting nuclear factor κB (NF-κB), it decreases tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) and has an anti-inflammatory effect. Endotoxin shock can induce the production of several inflammatory mediators such as TNF-α and IL-6, leading to multiple organ dysfunction and death. We investigated the effects of rosiglitazone (.3 mg/kg, intravenous administration) on the physiologic attributes and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae lipopolysaccharides (LPSs; 10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 24 hr after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), glucose, TNF-α, and IL-6 were measured at 0, 1, 3, 6, 12, and 24 hr after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, glucose, TNF-α, and IL-6 levels and HR, while also decreasing MAP. Rosiglitazone diminished the increase in HR, decreased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, CPK, glucose) and inflammatory biomarkers (TNF-α, IL-6), and did not affect MAP after LPS. In conclusion, rosiglitazone ameliorated endotoxin shock-induced markers of organ injury and suppressed the release of TNF-α and IL-6 in conscious rats.
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Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/toxicidade , Choque Séptico/tratamento farmacológico , Tiazolidinedionas/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Pressão Sanguínea/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Estado de Consciência , Creatina Quinase/sangue , Frequência Cardíaca/efeitos dos fármacos , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Masculino , Ratos , Ratos Endogâmicos WKY , Rosiglitazona , Choque Séptico/imunologia , Choque Séptico/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Ankle-brachial index (ABI) is an important indicator of peripheral arterial disease (PAD) and PAD has a negative impact on quality of life (QOL). However, the correlation between ABI and QOL is unknown among chronic hemodialysis patients. Ankle-brachial index was measured, and WHOQOL-BRIEF (TW) questionnaire was completed. The association between ABI and QOL was analyzed using linear regression. A total of 54 chronic hemodialysis patients (mean age of 56.2 +/- 14.6 years) were included. Ankle-brachial index was positively associated with QOL (r = .448, P = .001). The QOL scores were 3.1 +/- 2.9 and 2.6 +/- 0.4 for 37 patients with an ABI more than 0.9 and 17 patients with an ABI less than 0.9 or more than 1.3 (p < .001). In linear regression, only ABI was significantly associated with QOL scores with a beta of .448 (95% CI: 0.443 to 1.55, P = .001). Ankle-brachial index is positively correlated to QOL among chronic hemodialysis patients.
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Índice Tornozelo-Braço , Doenças Vasculares Periféricas/fisiopatologia , Qualidade de Vida , Diálise Renal , Análise Química do Sangue , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estatísticas não ParamétricasRESUMO
BACKGROUND: Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate-induced PF in rats. MATERIALS AND METHODS: The PF was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low-dose aliskiren (1 mg kg(-1)) or high-dose aliskiren (10 mg kg(-1)) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. RESULTS: There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D(4)/P(4) urea level was reduced, the D(4)/D(0) glucose level, serum and dialysate transforming growth factor-beta1 (TGF-beta1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF-beta1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta1, alpha-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. Moreover, high-dose aliskiren had better protective effects against PF than low dose in rats. CONCLUSIONS: Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta1 production.
Assuntos
Amidas/administração & dosagem , Clorexidina/análogos & derivados , Fumaratos/administração & dosagem , Fibrose Peritoneal/induzido quimicamente , Renina/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo , Animais , Anti-Infecciosos/efeitos adversos , Clorexidina/administração & dosagem , Clorexidina/efeitos adversos , Diálise Peritoneal/efeitos adversos , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
OBJECTIVE: Hypoadiponectemia was observed to correlate with the prevalence or extent of coronary artery disease (CAD), the relationship between metabolic syndrome and fasting serum adiponectin concentration in CAD patients are not well elucidated. PATIENTS AND METHODS: Fasting blood samples were obtained from 98 CAD patients. Metabolic syndrome and its components were defined using the diagnostic criteria of the International Diabetes Federation. Adiponectin concentrations were measured using a commercial enzyme immunoassay kit. RESULTS: Fifty patients with CAD (51.0%) had metabolic syndrome. For this group of patients, fasting adiponectin concentrations were found to correlate inversely with metabolic syndrome (p=0.009). Fasting adiponectin values for these subjects also tended to decrease as the number of diagnostic criteria for metabolic syndrome increased (p=0.024). CAD patients with hyperlipidemia (p=0.002), obesity (p=0.030) or receiving statin therapy (p=0.005) had lower serum adiponectin values. By univariate linear regression analysis, fasting serum adiponectin values were positively correlated with age (r=0.242; p=0.017) and high density lipoprotein-cholesterol concentration (HDL-cholesterol; r=0.267; p=0.008) but were negatively correlated with triglyceride concentration (TG; r=-0.251; p=0.013). Multivariate forward stepwise linear regression analysis of the significant variables revealed that HDL-cholesterol concentration (R square=0.071, p=0.008) and age (R square=0.039, p=0.044) are the independent predictors of fasting serum adiponectin concentration for patients with CAD. CONCLUSION: Serum adiponectin concentration is inversely correlated with metabolic syndrome and the number of metabolic syndrome criteria in patients with CAD. For these patients HDL-cholesterol concentration and age are independent predictors of the serum adiponectin value.
Assuntos
Adiponectina/sangue , Doença da Artéria Coronariana/sangue , Jejum/sangue , Síndrome Metabólica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , HDL-Colesterol/sangue , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Our aim was to evaluate the relationship between metabolic syndrome and fasting serum leptin concentration in renal transplant recipients. PATIENTS AND METHODS: Fasting blood samples were obtained from 55 renal transplant recipients. Metabolic syndrome and its components were defined using the diagnostic criteria of the International Diabetes Federation. RESULTS: Thirteen patients (23.6%) had metabolic syndrome. Fasting leptin concentrations were positively correlated with metabolic syndrome (p=0.003). Univariate linear regression analysis indicated fasting serum leptin values were positively correlated with waist circumference (r=0.284; p=0.036), body mass index (r=0.358; p=0.007), body fat mass (r=0.610; p<0.001), triglycerides (r=0.268; p=0.048), high-sensitivity C-reactive protein (hs-CRP) (r=0.377; p=0.005), triceps skinfold (r=0.335; p=0.012), and mid-arm fat area (r=0.351; p=0.009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that body fat mass (R2 change=0.373; p<0.001) and hs-CRP (R2 change=0.045; p=0.049) were the independent predictors of fasting serum leptin concentration. CONCLUSION: Serum leptin concentration correlates positively with metabolic syndrome in renal transplant recipients.