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1.
J Adv Nurs ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38779925

RESUMO

AIM: To identify key factors that influence personal care workers' (PCW) intention to stay in residential aged care (RAC). BACKGROUND: PCWs are the 'backbone' of providing direct care in RAC settings. The well-being of older people hinges upon their dedication and commitment; thus, enhancing their intention to stay is a priority to reduce turnover and ensure continuity of care. METHODS: Six databases were searched for articles focusing on factors influencing PCWs' intention to stay in RAC. Studies were independently assessed for quality using the Joanna Briggs Institute Methodology for systematic review tools. Reporting of the results followed the PRISMA guidelines. FINDINGS: Eight articles published between 2010 and 2022 were included. The key issues were categorized as: (a) sociodemographic characteristics; (b) psychological factors; (c) workplace factors and (d) job satisfaction. Older age, being married and immigration status were positively associated with intention to stay. Work stress and burnout contributed towards demotivation, while a supportive and engaging organizational culture that recognized workers' contributions and provided appropriate remuneration and benefits, enhanced job satisfaction and retention. CONCLUSION: This review affirms the complexity of the decision-making process influencing workers' intention to stay. A comprehensive understanding of the interplay of these factors and the personal and sociocultural challenges faced by PCWs is essential to design strategies to provide support and enhance job satisfaction and retention. IMPLICATIONS FOR AGED CARE: This review showed that support from the organization is critical in improving PCWs' intention to stay in aged care. Given the interconnectedness of a range of key factors, decision-makers need to address modifiable factors holistically. Including PCWs in planning retention strategies could be the missing link in tailoring interventions towards workforce retention. IMPACT: Personal, psychological and workplace factors alone and in combination influence personal care workers' intention to stay in residential aged care (RAC). The interrelationships among the factors impacting PCWs' intention to stay are complex, wherein a change in one often influences other factors. Addressing the causes of psychological stress, improving workplace culture and understanding their interrelationships provide a foundation for co-designing strategies to promote intention to stay among PCWs in RAC. REPORTING METHOD: The authors have adhered to relevant EQUATOR guidelines PRISMA. NO PATIENT OR PUBLIC CONTRIBUTION: This integrative review is conducted with no involvement or contribution from patients or the public.

2.
Anal Chem ; 95(46): 17082-17088, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37937965

RESUMO

Biothreat detection has continued to gain attention. Samples suspected to fall into any of the CDC's biothreat categories require identification by processes that require specialized expertise and facilities. Recent developments in analytical instrumentation and machine learning algorithms offer rapid and accurate classification of Gram-positive and Gram-negative bacterial species. This is achieved by analyzing the negative ions generated from bacterial cell extracts with a modified linear quadrupole ion-trap mass spectrometer fitted with two-dimensional tandem mass spectrometry capabilities (2D MS/MS). The 2D MS/MS data domain of a bacterial cell extract is recorded within five s using a five-scan average after sample preparation by a simple extraction. Bacteria were classified at the species level by their lipid profiles using the random forest, k-nearest neighbor, and multilayer perceptron machine learning models. 2D MS/MS data can also be treated as image data for use with image recognition algorithms such as convolutional neural networks. The classification accuracy of all models tested was greater than 99%. Adding to previously published work on the 2D MS/MS analysis of bacterial growth and the profiling of sporulating bacteria, this study demonstrates the utility and information-rich nature of 2D MS/MS in the identification of bacterial pathogens at the species level when coupled with machine learning.


Assuntos
Bactérias , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Algoritmos , Redes Neurais de Computação , Aprendizado de Máquina
3.
Int J Nurs Stud ; 146: 104568, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37597458

RESUMO

BACKGROUND: Depression in older people living in residential aged care is a serious and highly prevalent health issue, with loneliness and social isolation being major contributors. The COVID-19 pandemic underscored the harm visiting restrictions have on the mental wellbeing of older people in residential aged care. However, there is a need to systematically review the relationship between family visits and depression in this population. OBJECTIVE: This literature review seeks to explore the association between family visits and depression among those living in residential aged care. METHODS: An integrative review was conducted in March 2022, based on a search of seven databases from inception to 2022. Papers were included if the studies were situated in a residential aged care facility and explored the impact of in-person family visits on depression of residents. Those that examined impact of family visits on community-dwelling older people and papers examining virtual family visits were excluded. The quality of the included papers was assessed using appropriate critical appraisal tools. Guided by the aim of this study, the included papers were narratively synthesised and presented thematically (PROSPERO ID CRD42022325895). RESULTS: Ten papers, published between 1991 and 2022, were included in the final synthesis. Multiple categorisations of frequency of visits and different scales were used to assess depression. Depression among residents in aged care facilities varied from 20 % to 58.7 % with 40 % of studies showing a positive association between the frequency of family visits and lower rate of depression. Three themes influencing the association between family visits and depression in residential aged care were identified. These were: (i) intersection of culture, filial values, and depression; (ii) resident-related factors including whether admission was voluntary and presence of functional impairment; and (iii) non-resident-related factors such as social activities for residents and staff involvement. CONCLUSION: Family visits ameliorated loneliness and depression among residents in aged care however, other factors such as culture, comorbidities and functional impairment, opportunities for socialisation and the social involvement of facility staff also influenced depression. Whilst the low number of studies reviewed limited comparison and generalisation of results, the review highlighted the broader and crucial role of healthcare staff in facilitating socialisation and promoting mental wellbeing of residents especially those who are not visited by families. TWEETABLE ABSTRACT: Family visits ameliorate depression in institutionalised older people but may not be the "silver bullet" as depression is multifactorial.


Assuntos
COVID-19 , Pandemias , Idoso , Humanos , Instituição de Longa Permanência para Idosos , Atenção à Saúde , Vida Independente
4.
J Invest Dermatol ; 143(11): 2243-2254.e10, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37211203

RESUMO

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFß/NF-κB, SMAD7 blunted IL-22/signal transducer and activator of transcription 3 activation and associated pathogenesis, which is due to SMAD7 transcriptionally upregulating IL-22 antagonist IL-22RA2. Mechanistically, SMAD7 facilitated nuclear translocation and DNA binding of C/EBPß to IL22RA2 promoter for IL22RA2 transactivation. Consistent with the observations in mice mentioned earlier, transcript levels of IL22RA2 were increased in human atopic dermatitis and psoriasis lesions with clinical remission. Our study identified the anti-inflammation functional domain of SMAD7 and suggests the mechanism and feasibility for developing SMAD7-based biologics as a topical therapy for skin inflammatory disorders.


Assuntos
Dermatite , Psoríase , Receptores de Interleucina , Camundongos , Humanos , Animais , Imiquimode/farmacologia , Proteína Smad7/genética , Pele/patologia , Psoríase/tratamento farmacológico , Psoríase/genética , Psoríase/induzido quimicamente , Dermatite/patologia , Queratinócitos/metabolismo , Inflamação/patologia , Fenótipo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
5.
Int J Mol Sci ; 24(7)2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37047183

RESUMO

Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor potential vanilloid 1 (TRPV1) channel in afferent renal nerves suppresses RSNA and prevents renal dysfunction and hypertension in obese rats. N-oleoyldopamine (OLDA, 1 ng/kg, daily) was administrated intrathecally (T8-L3) via an indwelled catheter to chronically activate, TRPV1-positive afferent renal nerves in rats fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD intake significantly increased the body weight, impaired glucose and insulin tolerance, decreased creatinine clearance, and elevated systolic blood pressure in rats compared with the levels of the chow-fed rats (all p < 0.05). An intrathecal OLDA treatment for 8 weeks did not affect the fasting glucose level, glucose tolerance, and insulin tolerance in rats fed either chow or HFD. As expected, the chronic OLDA treatment significantly increased the levels of plasma calcitonin gene-related peptide and substance P and ARNA in the HFD-fed rats (all p < 0.05). Interestingly, the OLDA treatment decreased the urinary norepinephrine level and RSNA in rats fed HFD (both p < 0.05). Importantly, the OLDA treatment attenuated HFD-induced decreases in creatinine clearance and urinary Na+ excretion and increases in the plasma urea level, urinary albumin level, and systolic blood pressure at the end of an 8-week treatment (all p < 0.05). Taken together, the intrathecal administration of OLDA ameliorates the enhancement of RSNA, renal dysfunction, and hypertension in obese rats. These findings shed light on the roles of TRPV1-positive renal afferent nerves in obesity-related renal dysfunction and hypertension.


Assuntos
Hipertensão , Insulinas , Nefropatias , Animais , Ratos , Creatinina , Dieta Hiperlipídica , Glucose , Hipertensão/prevenção & controle , Rim/fisiologia , Rim/inervação , Obesidade/tratamento farmacológico , Obesidade/etiologia , Canais de Cátion TRPV/genética
6.
PLoS One ; 17(9): e0274618, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36103570

RESUMO

Age-related cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction which lacks ideal treatment. Transient receptor potential ankyrin 1 (TRPA1) is an oxidative stress sensor and could attenuate age-related pathologies in invertebrates. The present study aimed to test whether TRPA1 plays a role in age-related cardiac remodeling and dysfunction. The cardiac function and pathology of 12-week-old (young) and 52-week-old (older) Trpa1-/- mice and wild-type (WT) littermates were evaluated by echocardiography and histologic analyses. The expression levels of 84 fibrosis-related genes in the heart were measured by quantitative polymerase chain reaction array. Young Trpa1-/- and WT mice had similar left ventricular wall thickness, volume, and systolic and diastolic function. Older Trpa1-/- mice had significantly increased left ventricular internal diameter and volume and impaired systolic (lower left ventricular ejection fraction) and diastolic (higher E/A ratio and isovolumetric relaxation time) functions compared with older WT mice (P<0.05 or P<0.01). Importantly, older Trpa1-/- mice had enhanced cardiac fibrosis than older WT mice (P<0.05) while the two strains had similar degree of cardiac hypertrophy. Among the 84 fibrosis-related genes, Acta2, Inhbe, Ifng, and Ccl11 were significantly upregulated, while Timp3, Stat6, and Ilk were significantly downregulated in the heart of older Trpa1-/- mice compared with older WT mice. Taken together, we found that knocking out Trpa1 accelerated age-related myocardial fibrosis, ventricular dilation, and cardiac dysfunction. These findings suggest that TRPA1 may become a therapeutic target for preventing and/or treating cardiac fibrosis and heart failure with preserved ejection fraction in the elderly.


Assuntos
Insuficiência Cardíaca , Função Ventricular Esquerda , Animais , Cardiomegalia , Fibrose , Camundongos , Camundongos Knockout , Volume Sistólico/genética , Canal de Cátion TRPA1/genética , Função Ventricular Esquerda/fisiologia
7.
Biochem Pharmacol ; 203: 115190, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35905972

RESUMO

Western diet (WD) intake increases morbidity of obesity and salt-sensitive hypertension albeit mechanisms are largely unknown. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) in WD intake-induced hypertension. TRPV1-/- and wild-type (WT) mice were fed a normal (CON) or Western diet (WD) for 16-18 weeks. Mean arterial pressure (MAP) after normal sodium glucose (NSG) loading with or without L-NAME (a NO synthase inhibitor) or N-oleoyldopamine (OLDA, a TRPV1agonist) was not different between the two strains on CON.WT or TRPV1-/- mice fed WD had increased MAP after NSG, with a greater magnitude in TRPV1-/- mice. OLDA decreased while L-NAME increased MAP in WT-WD but not in TRPV1-/--WD mice. The urinary nitrates plus nitrites excretion (UNOx), an indicator of renal NO production, was increased in both strains on CON after NSG. TRPV1 ablation with WD intake abolished NSG-induced increment in UNOx. OLDA further increased while L-NAME prevented NSG-induced increment in UNOx in WT-WD mice. Urinary sodium excretion was increased in both strains on CON and in WT-WD mice but not in TRPV1-/--WD mice after NSG. OLDA further increased while L-NAME prevented NSG-induced increases in sodium excretion in WT-WD but not in TRPV1-/--WD mice. Thus, TRPV1 ablation increases salt sensitivity during WD intake possibly via impaired renal NO production and sodium excretion. Activation of TRPV1 enhances renal NO production and sodium excretion, resulting in prevention of increased salt sensitivity during WD intake.


Assuntos
Hipertensão , Natriurese , Animais , Dieta Hiperlipídica , Camundongos , Camundongos Knockout , NG-Nitroarginina Metil Éster/farmacologia , Sódio , Cloreto de Sódio , Canais de Cátion TRPV/genética
8.
Int J Ment Health Addict ; 20(3): 1814-1823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33519318

RESUMO

This study explored the relationship between alcohol and substance use in the general population during the early stages of COVID-19 as related to individual, family, and community stressors. A convenience sample of adults who resided in the USA and Canada was utilized. An online survey was conducted. Over one-third of the sample reported utilizing alcohol and substances as a means to cope during the pandemic. A linear regression revealed that use of social media as a source of information, being personally affected by COVID-19, experiencing child care challenges, and not being associated with a religious community were related to increased likeliness for alcohol and/or substance use. Future research should explore these concepts further within the general population.

9.
Int J Radiat Oncol Biol Phys ; 112(3): 759-770, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610386

RESUMO

PURPOSE: Recent studies reported therapeutic effects of Smad7 on oral mucositis in mice without compromising radiation therapy-induced cancer cell killing in neighboring oral cancer. This study aims to assess whether a Smad7-based biologic can treat oral mucositis in a clinically relevant setting by establishing an oral mucositis model in dogs and analyzing molecular targets. METHODS AND MATERIALS: We created a truncated human Smad7 protein fused with the cell-penetrating Tat tag (Tat-PYC-Smad7). We used intensity modulated radiation therapy to induce oral mucositis in dogs and applied Tat-PYC-Smad7 to the oral mucosa in dose-finding studies after intensity modulated radiation therapy. Clinical outcomes were evaluated. Molecular targets were analyzed in biopsies and serum samples. RESULTS: Tat-PYC-Smad7 treatment significantly shortened the duration of grade 3 oral mucositis based on double-blinded Veterinary Radiation Therapy Oncology Group scores and histopathology evaluations. Topically applied Tat-PYC-Smad7 primarily penetrated epithelial cells and was undetectable in serum. NanoString nCounter Canine IO Panel identified that, compared to the vehicle samples, top molecular changes in Tat-PYC-Smad7 treated samples include reductions in inflammation and cell death and increases in cell growth and DNA repair. Consistently, immunostaining shows that Tat-PYC-Smad7 reduced DNA damage and neutrophil infiltration with attenuated TGF-ß and NFκB signaling. Furthermore, IL-1ß and TNF-α were lower in Tat-PYC-Smad7 treated mucosa and serum samples compared to those in vehicle controls. CONCLUSIONS: Topical Tat-PYC-Smad7 application demonstrated therapeutic effects on oral mucositis induced by intensity modulated radiation therapy in dogs. The local effects of Tat-PYC-Smad7 targeted molecules involved in oral mucositis pathogenesis as well as reduced systemic inflammatory cytokines.


Assuntos
Mucosite , Lesões por Radiação , Estomatite , Animais , Cães , Produtos do Gene tat/metabolismo , Camundongos , Lesões por Radiação/complicações , Proteína Smad7/genética , Proteína Smad7/metabolismo , Estomatite/metabolismo , Fator de Crescimento Transformador beta/metabolismo
10.
Cells ; 10(5)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069822

RESUMO

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1-/- mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1-/- mice (p < 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1-/- mice (p < 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1-/- mice on WD (all p < 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1-/- mice (all p < 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p < 0.05) but not in TRPV1-/- mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p < 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1-/- mice (all p < 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1-/- mice (p < 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.


Assuntos
Inibidores de Ciclo-Oxigenase/toxicidade , Dieta Hiperlipídica , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Obesidade/tratamento farmacológico , Salicilato de Sódio/toxicidade , Sistema Nervoso Simpático/efeitos dos fármacos , Canais de Cátion TRPV/deficiência , Animais , Barorreflexo/efeitos dos fármacos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Deleção de Genes , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Rim/inervação , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Canais de Cátion TRPV/genética
11.
J Hum Rights Soc Work ; 6(3): 246-254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095456

RESUMO

It is a responsibility of national leadership to provide guidance and provisions to their citizens during a pandemic. National responses to the COVID-19 pandemic have greatly varied internationally. The purpose of this study was to compare how people in Canada and the USA coped to the COVID-19 pandemic, with an eye towards discerning if any differences relate to macro systems differences between the neighboring countries. Data were analyzed from an online, cross-sectional survey administered to people (N = 1405) living in Canada and the USA in June 2020. Significant results show that respondents from Canada were felt more prepared, adapted/coped better to the pandemic, had less life disruption, fewer challenges with healthcare and financially, and were personally less affected by the pandemic than respondents from the USA. Those from Canada also showed significant higher levels of support for both their national and provincial/state leadership and belief in the necessity of preventative measures than those in the USA. Respondents from the USA were more likely to use family and friends as a source of information and as a basis for their personal preventative practices, whereas those in Canada were more likely to follow the official government recommendations. There were no significant differences in methods of coping. These results support the need for a clear role of government and for government to respond to individuals in a way that promotes equity and social justice, and thus, ensuring human rights.

12.
Soc Work Health Care ; 60(3): 240-255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33407057

RESUMO

This study explored people's compliance with recommended preventative measures during early stages of the COVID-19 pandemic. An online survey was administered in June 2020 in the USA and Canada (N = 1,405). Regression analysis found that when controlling for other factors, age and political ideology were significant predictors of compliance with preventative measures. A content analysis of narrative answers of compliance/noncompliance found that the majority of individuals intended to comply with preventative measures, with primary reasons as social responsibility, self-protection, and protection of family members. Reasons identified for not complying were viewing preventative practices as unnecessary, getting mixed messages from various sources about effectiveness, distrust in government and inability to comply. This study informs social workers on intervention strategies on micro, mezzo and macro levels of practice.


Assuntos
COVID-19 , Fidelidade a Diretrizes , Pandemias/prevenção & controle , Adolescente , Adulto , Canadá , Controle de Doenças Transmissíveis/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Análise de Regressão , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
13.
Clin Exp Hypertens ; 43(3): 254-262, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33327798

RESUMO

Background: High-salt intake after renal ischemia/reperfusion (I/R) injury leads to hypertension and further renal injury, but the mechanisms are largely unknown. This study tested the hypothesis that degeneration of transient receptor potential vanilloid 1 (TRPV1)-positive nerves exacerbates salt-induced hypertension and renal injury after I/R via enhancing renal macrophage infiltration.Methods: Large dose of capsaicin (CAP, 100 mg/kg, subcutaneously) was used to degenerate rat TRPV1-positive nerves. Then, rats were subjected to renal I/R injury and fed with a low-salt (0.4% NaCl) diet for 5 weeks after I/R, followed by a high-salt (4% NaCl) diet for 4 weeks during which macrophages were depleted using liposome-encapsulated clodronate (LC, 1.3 ml/kg/week, intravenously).Results: The protein level of TRPV1 in the kidney was downregulated by renal I/R injury and was further decreased by CAP treatment. LC treatment did not affect the protein levels of renal TRPV1. After renal I/R injury, high-salt diet significantly increased renal macrophage infiltration, inflammatory cytokines (tumor necrosis factor-alpha and interleukin 1 beta), systolic blood pressure, the urine/water intake ratio, plasma creatine and urea levels, urinary 8-isoprostane, and renal collagen deposition. Interestingly, CAP treatment further increased these parameters. These increases were abolished by depleting macrophages with LC treatment.Conclusions: These data suggest that degenerating TRPV1-positive nerves exacerbates salt-induced hypertension and tissue injury in rats after renal I/R injury via macrophages-mediated renal inflammation.


Assuntos
Hipertensão/patologia , Macrófagos/patologia , Tecido Nervoso/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Cloreto de Sódio na Dieta/efeitos adversos , Canais de Cátion TRPV/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Capsaicina , Ácido Clodrônico/farmacologia , Fibrose , Hipertensão/fisiopatologia , Inflamação/patologia , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Macrófagos/metabolismo , Masculino , Tecido Nervoso/efeitos dos fármacos , Tecido Nervoso/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
14.
Am J Hypertens ; 34(1): 110-116, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33005917

RESUMO

BACKGROUND: Classically activated macrophages contribute to the development of renal ischemia-reperfusion injury (IRI). This study aimed to investigate the role of transient receptor potential ankyrin 1 (Trpa1), a regulator of macrophage activation, in IRI-induced acute kidney injury (AKI) by using the Trpa1 gene knockout (Trpa1-/-) mouse model. METHODS: Male 8-week-old Trpa1-/- mice and wild-type (WT) littermates were subjected to renal ischemia for 35 minutes by clamping bilateral renal pedicles under isoflurane anesthesia, and blood and tissue samples were collected 24 hours after reperfusion and analyzed with histological and molecular measurements. RESULTS: Following IRI, Trpa1-/- mice developed more deteriorated biochemical and morphological signs of AKI when comparing with WT mice. More classically activated M1 macrophages were found in the kidneys of Trpa1-/- mice comparing with WT mice after IRI, while the counts of alternatively activated M2 macrophages in the kidney were similar between the 2 strains after IRI. Furthermore, significantly higher expression levels of proinflammatory markers including interleukin-1 beta and tumor necrosis factor alpha were detected in the kidney of Trpa1-/- mice compared with WT mice after IRI. The levels of TRPA1 protein in the kidney of WT mice were also decreased after IRI. CONCLUSIONS: Our results show that ablation of Trpa1 exacerbates infiltration of classically activated macrophages, renal inflammation, and renal injury in mice after IRI. These findings suggest that activation of TRPA1 may protect against IRI-induced AKI via regulation of macrophage-mediated inflammatory pathway.


Assuntos
Hipertensão , Inflamação/metabolismo , Rim , Ativação de Macrófagos/imunologia , Traumatismo por Reperfusão , Canal de Cátion TRPA1/metabolismo , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Animais , Hipertensão/imunologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Fatores Imunológicos/análise , Interleucina-1beta/metabolismo , Rim/metabolismo , Rim/fisiopatologia , Camundongos , Camundongos Knockout , Fatores de Proteção , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo
15.
J Hum Hypertens ; 35(10): 859-869, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33093616

RESUMO

Hypertension is a risk factor for acute kidney injury. In this study, we aimed to identify the optimal blood pressure (BP) targets for CKD and non-CKD patients. We analyzed the data of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) to determine the nonlinear relationship between BP and renal disease development using the Generalized Additive Model (GAM). Optimal systolic BP/diastolic BP (SBP/DBP) with lowest renal risk were estimated using GAM. Logistic regression was employed to find odds ratios (ORs) of adverse renal outcomes by three BP groups (high/medium/low). Both study trials have demonstrated a "U"-shaped relationship between BP and renal outcomes. For non-CKD patients in SPRINT trial, risk of 30% reduction in eGFR among intensive group patients with DBP ≤ 70 mmHg was significantly higher than the group with DBP between 71 and 85 mmHg (OR = 2.31, 95% CI = 1.51-3.53). For non-CKD patients in ACCORD trial, risk of doubling of serum creatinine (SCr) or >20 mL/min decrease in eGFR among intensive group patients with DBP ≤ 70 mmHg was significantly higher than the group with DBP between 71 and 85 mmHg (OR = 1.49, 95% CI = 1.12-1.99). For CKD patients in SPRINT trial, there are no significant differences in renal outcomes by different SBP/DBP levels. Our analysis of both SPRINT and ACCORD datasets demonstrated that lower-than-optimal DBP may lead to poor renal outcomes in non-CKD patients. Healthcare providers should be cautious of too low DBP level in intensive BP management due to poor renal outcomes for non-CKD patients.


Assuntos
Hipertensão , Nefropatias , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Taxa de Filtração Glomerular , Humanos , Hipertensão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
In Vivo ; 34(5): 2259-2268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871748

RESUMO

BACKGROUND/AIM: Transient receptor potential vanilloid type 1 (TRPV1) has anti-inflammatory properties. The present study aimed to investigate the role of TRPV1 in renal inflammatory responses and tissue injury following renal ischemia-reperfusion (I/R) in diet-induced obese mice. MATERIALS AND METHODS: TRPV1 knockout and wild type mice were fed a normal or western diet (WD) for 23 weeks and were then subjected to renal I/R injury. RESULTS: TRPV1 knockout mice showed enhanced WD-induced renal macrophage infiltration and collagen deposition. Knocking out TRPV1 exacerbated renal I/R-induced increase of malondialdehyde, interleukin-6, monocyte chemoattractant protein-1, and NF-ĸB in obese mice. Similar results were observed in the expression of phosphorylated Smad1 and Smad2/3. Blockade of calcitonin gene-related peptide (CGRP) receptors with CGRP8-37 worsened the I/R-induced renal inflammation and injury. CONCLUSION: Our data indicate that preserving TRPV1 expression and function may prevent renal I/R injury in obesity likely through alleviating inflammatory responses.


Assuntos
Traumatismo por Reperfusão , Canais de Cátion TRPV , Animais , Inflamação/genética , Isquemia , Camundongos , Camundongos Knockout , Camundongos Obesos , Reperfusão , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/genética , Canais de Cátion TRPV/genética
17.
Curr Hypertens Rev ; 16(2): 148-155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31721716

RESUMO

BACKGROUND: Salt sensitivity is increased following renal Ischemia-Reperfusion (I/R) injury. We tested the hypothesis that high salt intake induced increase in Renal Sympathetic Nerve Activity (RSNA) after renal I/R can be prevented by activation of Transient Receptor Potential Vanilloid 1 (TRPV1). METHODS: Rats were fed a 0.4% NaCl diet for 5 weeks after renal I/R, followed by a 4% NaCl diet for 4 more weeks in four groups: sham, I/R, I/R +High Dose Capsaicin (HDC), and I/R+Low Dose Capsaicin (LDC). The low (1mg/kg) or high (100mg/kg) dose of capsaicin was injected subcutaneously before I/R to activate or desensitize TRPV1, respectively. RESULTS: Systolic blood pressure was gradually elevated after fed on a high-salt diet in the I/R and I/R+HDC groups but not in the I/R+LDC group, with a greater increase in the I/R+HDC group. Renal function was impaired in the I/R group and was further deteriorated in the I/R+HDC group but was unchanged in the I/R+LDC group. At the end of high salt treatment, afferent renal nerve activity in response to unilateral intra-pelvic administration of capsaicin was decreased in the I/R group and was further suppressed in the I/R+HDC group but was unchanged in the I/R+LDC group. RSNA in response to intrathecal administration of muscimol, a selective agonist of GABA-A receptors, was augmented in the I/R group and further intensified in the I/R+HDC group but was unchanged in the I/R+LDC group. Similarly, urinary norepinephrine levels were increased in the I/R group and were further elevated in the I/R+HDC group but unchanged in the I/R+LDC group. CONCLUSION: These data suggest that TRPV1 activation prevents renal I/R injury-induced increase in salt sensitivity by suppressing RSNA.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Capsaicina/farmacologia , Hipertensão/prevenção & controle , Rim/inervação , Traumatismo por Reperfusão/prevenção & controle , Fármacos do Sistema Sensorial/farmacologia , Cloreto de Sódio na Dieta , Sistema Nervoso Simpático/efeitos dos fármacos , Canais de Cátion TRPV/agonistas , Animais , Modelos Animais de Doenças , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Canais de Cátion TRPV/metabolismo
18.
J Clin Nurs ; 29(3-4): 626-637, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31769898

RESUMO

AIMS AND OBJECTIVES: To explore the experiences of food choice and meal service in residential aged care facilities and its impact on autonomy, self-determination and quality of life from the perspectives of both residents and staff. BACKGROUND: Globally, residential aged care is a principal provider of care for older people who can no longer live independently at home. Within this setting, lack of food choice has been identified as a significant factor impacting on residents' self-determination, sense of autonomy and quality of life. DESIGN: This study used an exploratory descriptive qualitative approach guided by self-determination theory. METHOD: A total of 14 participants (seven residents and seven staff members) from two Australian residential aged care facilities were recruited through purposive and snowball sampling with assistance from one independent contact nurse at each facility. In-depth, semi-structured interviews were conducted, digitally recorded and transcribed. The COREQ checklist was used in this qualitative study. RESULTS: Three main themes were identified from the interview data provided by residents and staff, which were as follows: (a) catering for the masses; (b) organisational barriers to providing choice; and (c) food impacts well-being. CONCLUSIONS: This study explored the experiences of food choice and service in residential aged care facilities, from the perspectives of both residents and staff. Results of interviews highlighted the importance of providing adequate food choice which has become an enduring issue that requires more attention and commitment to make a positive change for residents living in residential aged care facilities. RELEVANCE TO CLINICAL PRACTICE: Nurses and other staff working in residential aged care facilities need to be aware of the importance of providing adequate food choice, including for residents who require modified diets. As advocates for residents, nursing staff must address the persistent lack of food choice. However, this will require a radical change in organisational culture and strong leadership.


Assuntos
Preferências Alimentares , Instituição de Longa Permanência para Idosos/organização & administração , Casas de Saúde/organização & administração , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Humanos , Cultura Organizacional , Pesquisa Qualitativa , Qualidade de Vida
19.
Artigo em Inglês | MEDLINE | ID: mdl-31513001

RESUMO

BACKGROUND: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity. METHODS: TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 µmol/L) and SP (0.1 µmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left Ventricular Developed Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured. RESULTS: HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP. CONCLUSION: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.


Assuntos
Traumatismo por Reperfusão Miocárdica/metabolismo , Obesidade/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Glicemia/metabolismo , Capsaicina/farmacologia , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/genética , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/genética
20.
Exp Ther Med ; 18(5): 3636-3642, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602241

RESUMO

This study tests the hypothesis that the lipoxygenase (LOX) pathway mediates protease-activated receptor (PAR) 2-induced activation of the transient receptor potential vanilloid receptor 1 (TRPV1) to protect the heart from ischemia/reperfusion (I/R) injury. SLIGRL, a PAR2 activating peptide, was administered prior to reperfusion following left anterior descending coronary artery ligation in wild type (WT) and TRPV1 knockout (TRPV1-/-) mice. In a Langendorffly perfused heart I/R model, hemodynamic parameters, including left ventricular end-diastolic pressure, left ventricular developed pressure, coronary blood flow and left ventricular peak +dP/dt were evaluated after I/R. SLIGRL reduced the cardiac infarct size in WT and TRPV1-/- mice with a greater effect in the former strain (P<0.05). SLIGRL increased plasma levels of calcitonin gene-related peptide (CGRP) and substance P in WT (both P<0.05) but not in TRPV1-/- mice. Pretreatment with CGRP8-37 (a CGRP receptor antagonist) or RP67580 (a neurokinin-1 receptor antagonist) alone had no effect on SLIGRL-induced cardiac protection in either strain. However, combined administration of CGRP8-37 and RP67580 abolished SLIGRL-induced cardiac protection in WT but not in TRPV1-/- mice. Nordihydroguaiaretic acid (a general LOX inhibitor) and baicalein (a 12-LOX inhibitor), but not indomethacin (a cyclooxygenase inhibitor) and hexanamide (a selective cytochrome P450 epoxygenase inhibitor), abolished the protective effects of SLIGRL in WT (all P<0.05) but not in TRPV1-/- hearts. These data suggested that PAR2, possibly via 12-LOX, activates TRPV1 and leads to CGRP and substance P release to prevent I/R injury in the heart, indicating that the 12-LOX-TRPV1 pathway conveys cardiac protection to alleviate myocardial infarction.

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