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2.
Cureus ; 15(6): e40298, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37448382

RESUMO

Background Obesity and illicit drugs are independent risk factors for developing heart failure (HF). However, recent studies have suggested that patients who already have HF and are obese have better clinical outcomes. We aim to study the effect of cocaine use on this obesity paradox phenomenon as it pertains to HF readmissions. Methodology In a retrospective chart analysis, we reviewed patients with a diagnosis of HF with reduced ejection fraction (HFrEF) admitted to Metropolitan Hospital in New York. We studied the association between body mass index (BMI) categories, namely, non-obese (<30 kg/m2) and obese (≥30 kg/m2), cocaine use, and the primary outcome (time to readmission for HF within 30 days after discharge). The interaction between cocaine and obesity status and its association with the primary outcome was also assessed. Results A total of 261 patients were identified. Non-obese status and cocaine use were associated with an increased hazard of readmission in 30 days (hazard ratio (HR) = 2.28, p = 0.049 and HR = 3.12, p = 0.004, respectively). Furthermore, cocaine users who were non-obese were over six times more likely to be re-admitted in 30 days compared to non-cocaine users who were obese (HR = 6.45, p = 0.0002). Conclusions Non-obese status and continued use of cocaine have a negative additive effect in impacting HF readmissions.

3.
West Afr J Med ; 39(9): 922-927, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36126320

RESUMO

BACKGROUND: The impact of lifestyle choices on health has received more attention in recent years due to several scientific studies that have found positive results between diseases and quality of life. This study determined factors influencing Health Promoting Lifestyles among Obafemi Awolowo University undergraduates. METHODS: This study employed a descriptive cross-sectional design. A multistage sampling technique was used in this study. Data were collected from 401 undergraduates using the Health Promoting Lifestyle Profile II (HPLP II) questionnaire which was adapted from previous studies. Multiple regression analysis was used to analyze the effects of various demographics on the overall HPLP-II score. The association was determined using a 95% confidence interval and a p-value less than 5% was taken as statistically significant. RESULTS: The average total HPLP II score among respondents was 131.2 ±18.4. The other dimensions of health promoting life style are health responsibility, physical activity, nutrition, stress management, self-actualization, and interpersonal relationships. Students had the highest mean scores in self-actualization among males (27.8±5.4) and females (27.7±5.2). Physical activity had the lowest mean score in both males (17.3±4.9) and females (15.9±4.7). There was a statistically significant difference in mean score of physical activity for male and female (t=2.805, p =0.005). The predictors of dimensions of health promoting life style were age (p=0.042), faculty (p=0.026), level of study (0.004) and religion (0.013). CONCLUSION: The study concluded that there is a statistically significant relationship between health promoting lifestyle and age, religion and respondents study level.


CONTEXTE: L'impact des choix de mode de vie sur la santé a fait l'objet d'une attention accrue ces dernières années en raison de plusieurs études scientifiques qui ont révélé des résultats positifs entre les maladies et la qualité de vie. Cette étude a déterminé les facteurs influençant les modes de vie favorables à la santé chez les étudiants de premier cycle de l'Université Obafemi Awolowo. MÉTHODES: Cette étude a utilisé un plan descriptif transversal. Une technique d'échantillonnage à plusieurs degrés a été utilisée dans cette étude. Les données ont été recueillies auprès de 401 étudiants de premier cycle à l'aide du questionnaire Health Promoting Lifestyle Profile II (HPLP II), adapté d'études antérieures. Une analyse de régression multiple a été utilisée pour analyser les effets de diverses données démographiques sur le score global du HPLP-II. L'association a été déterminée en utilisant un intervalle de confiance de 95 % et une valeur p inférieure à 5 % a été considérée comme statistiquement significative. RÉSULTATS: Le score total moyen de HPLP II parmi les répondants était de 131,2 ±18,4. Les autres dimensions du style de vie favorisant la santé sont la responsabilité en matière de santé, l'activité physique, la nutrition, la gestion du stress, l'accomplissement de soi et les relations interpersonnelles. Les étudiants ont obtenu les scores moyens les plus élevés en matière de réalisation de soi chez les hommes (27,8±5,4) et les femmes (27,7±5,2). L'activité physique a obtenu le score moyen le plus faible chez les hommes (17,3±4,9) et les femmes (15,9±4,7). Il y avait une différence statistiquement significative dans le score moyen de l'activité physique pour les hommes et les femmes (t=2,805, p =0,005). Les prédicteurs des dimensions du style de vie favorisant la santé étaient l'âge (p=0,042), la faculté (p=0,026), le niveau d'étude (0,004) et la religion (0,013). CONCLUSION: L'étude a conclu qu'il existe une relation statistiquement significative entre le style de vie favorisant la santé et l'âge, la religion et le niveau d'étude des répondants. Mots clés: Modes de vie favorables à la santé, maladies non transmissibles, étudiants de premier cycle, variables prédictives.


Assuntos
Comportamentos Relacionados com a Saúde , Qualidade de Vida , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Nigéria/epidemiologia , Estudantes , Universidades
4.
Babcock Univ. Med. J ; 4(1): 8-13, 2021.
Artigo em Inglês | AIM (África) | ID: biblio-1291975

RESUMO

Objectives: Human Immunodeficiency Virus (HIV) remains a public health issue with more than 25 million deaths since 1990. As of 2019, Nigeria has a national prevalence of 1.4% among 15-49 years and about 1.9 million people living with HIV, according to the Joint United Nations Programme on HIV/AIDS. This study assessed the factors responsible for unsuppressed viral load among patients accessing care at Federal Medical Centre HIV Clinic in Abeokuta, southwest Nigeria.Methods: The study design was descriptive cross-sectional. Data was collected using the qualitative method; an In-depth interview was conducted among 20 virally unsuppressed HIV patients currently on Antiretroviral Therapy (ART) at Federal Medical Centre Abeokuta. The participants were purposively selected. The data were analyzed using thematic analysis.Results: Although almost all the participants were aware of HIV, their knowledge of HIV was inadequate. Non-adherence to drugs, side effects of medications, the psychological effects of the disease, forgetfulness, and combination of anti-retroviral drugs with local herbs and alcohol were the associated factors of viral non-suppression among the patients.Conclusion: Scaling up psychological care services using Short Message Services (SMS) to improve viral suppression is, therefore, strongly recommended.


Assuntos
Humanos , Masculino , Feminino , Infecções por HIV , Carga Viral , Terapia Antirretroviral de Alta Atividade , Cooperação do Paciente
5.
Appl Ergon ; 89: 103219, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32854826

RESUMO

While there is wide evidence that the occupational use of hand tools increases the risk of musculoskeletal disorder, evidence is limited regarding manual scissors, commonly used by custom tailors for bespoke garment production. We assessed whether scissor design impacts physical demands (muscle activity, perceived discomfort, and wrist posture) and task performance (quality and perceived efficiency). Twenty-four novice volunteers each completed simulated cutting tasks in 24 conditions involving the factorial combinations of four scissor designs (SD), three workstation heights, and two fabric types. SD significantly affected all outcome measures, and differences between SDs were consistent across workstation heights and fabric types. Two wide-handles scissors appeared superior overall, which may be related to the distinct grip type employed with this type of design. These results suggest that careful scissor selection has the potential to both reduce injury risk and enhance performance during fabric cutting tasks, though future testing is needed under more realistic conditions.


Assuntos
Desenho de Equipamento , Esforço Físico/fisiologia , Indústria Têxtil/instrumentação , Trabalho/fisiologia , Trabalho/psicologia , Adulto , Simulação por Computador , Ergonomia , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Contração Muscular , Doenças Musculoesqueléticas/prevenção & controle , Doenças Profissionais/prevenção & controle , Postura/fisiologia , Análise e Desempenho de Tarefas , Punho/fisiologia
6.
Cureus ; 12(7): e9392, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32850258

RESUMO

Transthyretin cardiac amyloidosis results from the deposition of transthyretin amyloid fibrils in the myocardium. This happens because of the misfolding of genetically normal (wild type - ATTR) or mutant (hereditary ATTR) transthyretin. The clinical presentation of hereditary ATTR cardiac amyloidosis is dependent on the exact site of the amino acid substitution. The V122I gene mutation is most common among people of African descent and usually manifests with cardiomyopathy. The mutations are transmitted in an autosomal dominant manner with variable penetrance and associated with clinical features occurring most commonly after the age of 40. The symptoms of heart failure (HF) may be preceded by several years of vague neurological symptoms which is more concerning if there is no clear explanation. A high index of suspicion is therefore crucial in ensuring prompt diagnosis and therapy, as this may favorably alter the gloomy prognosis associated with cardiac amyloidosis.

7.
Soc Work Public Health ; 35(5): 261-270, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32660362

RESUMO

Pica is simply defined as the consumption of none food products such as laundry starch, clay dirt, ice, soap, and chalk. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classifies Pica as the habitual consumption of nonfood and non-nutritive substances for at least one year. Pica disorder is usually unnoticed, under-reported, causes serious harm to clients especially African American women, and seldom discussed in social work scholarship. It is, therefore, important to begin to sensitize social workers to the harmful effects of Pica, especially because it is often unrecognized and misdiagnoses can cause harm. This article provides a panoramic overview of Pica, the signs and symptoms of the disorder specifically among African American women and also address some of the adverse effects, and highlights some of the evidence-based effective treatment strategies. Finally, an urgent clarion call to social workers to conduct more research on Pica disorders among African American women is articulated.


Assuntos
Negro ou Afro-Americano , Pica , Negro ou Afro-Americano/estatística & dados numéricos , Feminino , Humanos , Pica/etnologia
8.
Soc Work Public Health ; 35(1-2): 47-67, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32156202

RESUMO

Genocide is a dehumanizing crime that threatens the welfare of any civilized society. Yet, before the annihilation of any targeted human group, the collective outcomes of the genocidal process (e.g., systemic desecrations) and genocidal death effect (e.g., years of mass deaths and death disparities) have often gone undetected, underestimated, or ignored by public health and human rights advocates. From1950-2010, the mass homicide-suicide killings engendering the premature deaths of Black males, ages15-24 years, corroborate that aspects of the genocidal process and genocidal death effect are happening in America. The mass killings of young Black males from these preventable homicide and suicide deaths are ethically alarming, and the determinants of death impacting their premature deaths command immediate primordial prevention and reinforced prevention efforts. An epidemiological genocide prevention matrix is explored as an innovative approach to address, prevent, and research premature deaths resulting from homicide and suicide, and genocidal death effect of young Black males. Undergirded by the Theory of Epidemiologic Transition, this article also examines the mass killings of young Black males through the genocidal and pragmatic lens. Death disparities, determinants of death, and genocidal death effect definitions are operationalized, and the Genocidal Death Effect Conceptual Framework is debuted in this article.


Assuntos
Negro ou Afro-Americano , Genocídio , Homicídio , Suicídio , Violência , Adolescente , Adulto , Humanos , Masculino , Vigilância da População , Saúde Pública , Estados Unidos
9.
Cureus ; 12(12): e12295, 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33520499

RESUMO

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which results in coronavirus disease 2019 (COVID-19) has had a devastating impact globally. Not much is fully understood about this disease. Acute respiratory distress syndrome (ARDS) appears to be the commonest complication among patients with COVID-19. However, venous thromboembolism (VTE) appears to be a common complication among patients with COVID-19 even with adequate anticoagulation during hospitalization. VTE may confer a poor outcome on its own or may exacerbate other common complications such as ARDS or cardiac injury. There are several diagnostic dilemmas with regards confirming VTE among patients with COVID-19 as there is a move to reduce the transfer of patients for angiographic studies or even venous Doppler ultrasonography because of the high transmissibility SARS-CoV-2. There is also the risk of worsening ARDS following fluid administration to prevent contrast nephropathy after angiographic studies.  It is, therefore, crucial to understand the timing of VTE occurrence in the setting of COVID-19, identify strategies for early diagnosis of VTE, therapeutic options as well as prognostic implications of VTE in the setting of COVID-19.

10.
Niger Postgrad Med J ; 26(3): 169-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31441455

RESUMO

BACKGROUND: Intussusception in adults is considered rare in surgical practice. It is the causative lesion in a small proportion of cases of intestinal obstruction and lower gastrointestinal bleeding. In the last decade, the incidence of adult intussusception appears to be increasing at our centre. AIMS: This study aims to document the pattern of presentation and management outcome of adult intussusception at our institution during the last decade. We also observed the occurring trends of this lesion. PATIENTS AND METHODS: This was a 10-year retrospective study of consecutive adult patients with intussusception seen at our institution from July 2008 to June 2018. Information on biodata, clinicopathological features and management outcome retrieved from case notes and pathology records were analysed on a personal computer using SPSS version 23. RESULTS: Twenty adult patients who had intussusception were seen during this period. There were 9 (45%) males and 11 (55%) females giving a male-to-female ratio of 1:1.2. The mean age of presentation was 45 (range 18-66) years. Clinical features were abdominal pain (85%), abdominal distension (80%), vomiting (70%), rectal bleeding (70%) and palpable abdominal mass (35%). Majority of patients (70%) presented with features of intestinal obstruction. Idiopathic intussusception (55%) accounted for more than half of the cases with the jejunoileal variety (30%) as the most common pathological type. One patient who had intussusception in the postoperative period was treated with manual reduction at laparotomy. Bowel resections were performed in the remaining 19 (95%) patients. CONCLUSION: Adult intussusception is still uncommon in our general surgical practice. Bowel resection is the mainstay of treatment.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Obstrução Intestinal/etiologia , Intussuscepção/diagnóstico , Intussuscepção/cirurgia , Dor Abdominal/etiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Intussuscepção/patologia , Masculino , Pessoa de Meia-Idade , Nigéria , Estudos Retrospectivos , Centros de Atenção Terciária , Vômito/etiologia , Adulto Jovem
11.
J Relig Health ; 57(3): 1095-1107, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29417396

RESUMO

This article explores the role the Black Church could play in facilitating spiritually sensitive, culturally relevant and gender-specific services to address the mental health and well-being of Black males. The help-seeking behaviors of Black men are examined as the authors offer two theories: the body, mind, spirit, environment, social, transcendent, and health, illness, men, and masculinities that may assist the Black Church in functioning as an effective support networks for healthy Black male mental health. Next, the authors discuss implications for practice, research, and education, and lastly, eight recommendations for Black Church leadership, social workers, and mental health professionals are also discussed.


Assuntos
Negro ou Afro-Americano/psicologia , Cristianismo , Comportamento de Busca de Ajuda , Masculinidade , Saúde Mental/etnologia , Religião e Psicologia , Clero , Humanos , Masculino , Estados Unidos
12.
Proc Natl Acad Sci U S A ; 114(43): E9163-E9171, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-29073113

RESUMO

The mostly widely used bronchodilators in asthma therapy are ß2-adrenoreceptor (ß2AR) agonists, but their chronic use causes paradoxical adverse effects. We have previously determined that ß2AR activation is required for expression of the asthma phenotype in mice, but the cell types involved are unknown. We now demonstrate that ß2AR signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. Our data show that inhibition of ß2AR signaling with an aerosolized antagonist attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsens these phenotypes, suggesting that ß2AR signaling on resident lung cells modulates the asthma phenotype. Labeling with a fluorescent ß2AR ligand shows the receptors are highly expressed in airway epithelium. In ß2AR-/- mice, transgenic expression of ß2ARs only in airway epithelium is sufficient to rescue IL-13-induced AHR, inflammation, and mucus production, and transgenic overexpression in WT mice exacerbates these phenotypes. Knockout of ß-arrestin-2 (ßarr-2-/-) attenuates the asthma phenotype as in ß2AR-/- mice. In contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted by ß2AR signaling. Together, these results suggest ß2ARs on airway epithelial cells promote the asthma phenotype and that the proinflammatory pathway downstream of the ß2AR involves ßarr-2. These results identify ß2AR signaling in the airway epithelium as capable of controlling integrated responses to IL-13 and affecting the function of other cell types such as airway smooth muscle cells.


Assuntos
Asma/etiologia , Eosinófilos/patologia , Células Epiteliais/metabolismo , Pulmão/patologia , Receptores Adrenérgicos beta 2/metabolismo , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Asma/patologia , Brônquios/citologia , Modelos Animais de Doenças , Epinefrina/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Interleucina-13/toxicidade , Pulmão/citologia , Metaplasia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais
13.
J Antimicrob Chemother ; 72(12): 3462-3470, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961905

RESUMO

BACKGROUND: The available treatment options for Clostridium difficile infection (CDI) are limited by high recurrence rates. Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial. OBJECTIVES: To assess surotomycin safety and clinical response (non-inferiority versus vancomycin) at the end of treatment (EOT) of CDI. Additionally, to assess surotomycin response over time and sustained response at 30-40 days post-EOT (superiority versus vancomycin). PATIENTS AND METHODS: Patients with CDI were randomized (1:1) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3, double-blind, multicentre, international trial. Clinical response over time and sustained clinical response were monitored until the end of the trial, through a follow-up period of 30-40 days. Clinical Trial Registration: NCT01598311. RESULTS: A total of 285 and 292 patients with confirmed CDI were randomized to receive surotomycin and vancomycin, respectively. Surotomycin-associated clinical response at EOT was non-inferior to vancomycin (surotomycin/vancomycin: 83.4%/82.1%; difference 1.4%, 95% CI - 4.9, 7.6). Following treatment with surotomycin, both clinical response over time (stratified log-rank test, P = 0.277) and sustained clinical response (63.3%/59.0%; difference 4.3%, 95% CI - 3.6, 12.2) did not demonstrate superiority versus vancomycin at end of trial. Both treatments were generally well tolerated. CONCLUSIONS: Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT. Surotomycin did not demonstrate superiority to vancomycin for clinical response over time or sustained clinical response rate.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Clostridium/tratamento farmacológico , Lipopeptídeos/administração & dosagem , Peptídeos Cíclicos/administração & dosagem , Vancomicina/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Método Duplo-Cego , Humanos , Lipopeptídeos/efeitos adversos , Pessoa de Meia-Idade , Peptídeos Cíclicos/efeitos adversos , Placebos/administração & dosagem , Resultado do Tratamento , Vancomicina/efeitos adversos , Adulto Jovem
14.
J Evid Inf Soc Work ; 13(4): 331-44, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26673281

RESUMO

Cancer incidence and mortality is a significant area of health disparity between African Americans and Caucasians. In the current article the authors used a systematic review design to examine the characteristics of different cancer media education intervention (CMEI) to increase access to cancer screenings for African Americans within a 30 year period (1980-2010). Ten computerized databases were searched using inclusion-exclusion criteria. Consequently, 179 potential studies were identified, and later reduced to 41 eligible studies through the inclusion-exclusion criteria. The eligible studies had a combined sample size of N = 12,764 respondents. The findings revealed that multi-media intervention strategies were the most common media intervention that led to increased cancer screenings among African Americans. The authors conclude with a call for social workers to be more involved in developing and following up with culturally appropriate media strategies that can increase the likelihood of early detection and successful treatment, thus reducing this important area of health disparity.


Assuntos
Negro ou Afro-Americano , Educação em Saúde/métodos , Meios de Comunicação de Massa/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/prevenção & controle , Detecção Precoce de Câncer/métodos , Conhecimentos, Atitudes e Prática em Saúde , Disparidades nos Níveis de Saúde , Humanos
15.
J Evid Inf Soc Work ; 13(1): 87-98, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25923773

RESUMO

Social work programs are experiencing unprecedented organizational changes due to budget cuts, dwindling resources, global, and technological challenges. However, there is limited information in the literature about the merger experiences of faculty in social work programs. On one hand undergoing merger and reorganization provides the opportunity to reorganize, reprioritize, re-assess, develop strategies, and explore previously untapped opportunities for social work programs. Conversely, merger experiences have caused frustration, intention to quit, confusion, and loss of professional identity for social work faculty. In this article the authors utilize a journaling method and sense-making approach of the merger experiences of some of the faculty members of a social work program in the United States. The authors suggest a framework to understand how the faculty confronted the challenges, overcame the pitfalls, and maximized the opportunities offered during the merger and organizational change process.


Assuntos
Docentes/organização & administração , Inovação Organizacional , Serviço Social/educação , Universidades/organização & administração , Comunicação , Comportamento Cooperativo , Meio Ambiente , Humanos , Relações Interpessoais , Cultura Organizacional , Meio Social , Integração de Sistemas , Incerteza , Estados Unidos
16.
Emerg Infect Dis ; 20(7): 1097-104, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24960614

RESUMO

In England and Wales, the emergence of Salmonella enterica serovar Enteritidis resulted in the largest and most persistent epidemic of foodborne infection attributable to a single subtype of any pathogen since systematic national microbiological surveillance was established. We reviewed 67 years of surveillance data to examine the features, underlying causes, and overall effects of S. enterica ser. Enteritidis. The epidemic was associated with the consumption of contaminated chicken meat and eggs, and a decline in the number of infections began after the adoption of vaccination and other measures in production and distribution of chicken meat and eggs. We estimate that >525,000 persons became ill during the course of the epidemic, which caused a total of 6,750,000 days of illness, 27,000 hospitalizations, and 2,000 deaths. Measures undertaken to control the epidemic have resulted in a major reduction in foodborne disease in England and Wales.


Assuntos
Infecções por Salmonella/epidemiologia , Salmonella enteritidis/isolamento & purificação , Animais , Galinhas/microbiologia , Surtos de Doenças , Ovos/microbiologia , Inglaterra/epidemiologia , Microbiologia de Alimentos/métodos , Humanos , Carne/microbiologia , País de Gales/epidemiologia
17.
Nat Prod Commun ; 7(12): 1673-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23413580

RESUMO

Essential oils obtained by hydrodistillation of leaves of two Nigerian species were analyzed for their constituents by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The leaf oil of Ficus benjamina L. (Moraceae), collected during the day, contained high contents of alpha-pinene (13.9%), abietadiene (9.7%), cis-alpha-bisabolene (8.2%) and germacrene-D-4-ol (8.4%), while the night sample was dominated by germacrene-D-4-ol (31.5%), 1,10-di-epi-cubenol (8.8%) and hexahydrofarnesylacetone (8.3%). This could be a possible indication of differences in emissions of volatiles by F. benjamina during the day and night. The main compounds of Irvingia barteri Hook. f. (Irvingiaceae) were beta-caryophyllene (17.0%), (E)-a-ionone (10.0%), geranial (7.6%), (E)-beta-ionone (6.6%) and beta-gurjunene (5.1%).


Assuntos
Ficus/química , Magnoliopsida/química , Óleos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas , Nigéria , Folhas de Planta/química , Espectrometria de Massas por Ionização por Electrospray
18.
Naunyn Schmiedebergs Arch Pharmacol ; 385(2): 203-10, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21964666

RESUMO

Glucocorticosteroids are the mainstay treatment for chronic asthma; however, adverse effects can limit their usefulness. We previously determined in experimental asthma that chronic administration of ß2-adrenoceptor inverse agonists reduced airway hyperresponsiveness and indexes of inflammation. However, the effect of co-administration of glucocorticosteroids with ß2-adrenoceptor inverse agonists is unknown. Therefore, we evaluated the anti-inflammatory effect of co-administration of dexamethasone, a glucocorticosteroid, and nadolol, a ß2-inverse agonist, in a murine asthma model. We measured eosinophils and cytokines in bronchoalveolar lavage fluid and mucin content in epithelial cells after exposure to different concentrations of dexamethasone and nadolol. Dexamethasone was administered for 3 days and nadolol for 24 days prior to ovalbumin challenge. Both drugs were continued during five daily intranasal challenges with ovalbumin. Independent administration of dexamethasone (0.4 mg/kg/day) or nadolol (25 ppm) reduced bronchoalveolar lavage eosinophils by 58% and 36%, respectively (P < 0.05). Co-administration of both drugs yielded an additive reduction in eosinophils (81%, P < 0.05). Co-administration of both drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) also yielded a greater reduction in mucin volume density (83%) than either drug alone (18% for dexamethasone and 62% for nadolol) and greater than high-dose dexamethasone (71%) alone (P < 0.05). Similarly, co-administration of both drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) yielded an additive effect on the reduction of type 2 cytokines in bronchoalveolar lavage fluid equivalent to the administration of a 10-fold higher dose of dexamethasone. In Summary, the simultaneous administration of a glucocorticosteroid and a ß2-adrenoceptor inverse agonist was more effective at reducing indexes of airway inflammation than either drug given alone; suggesting nadolol may possess "glucocorticoid-sparing" properties.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Nadolol/uso terapêutico , Animais , Asma/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos BALB C , Mucinas/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia
19.
Br J Pharmacol ; 160(5): 1105-18, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20590604

RESUMO

BACKGROUND AND PURPOSE: Antidepressants, which raise the CNS concentrations of 5-HT and noradrenaline, are frequently used in the treatment of chronic pain; however, it is not known if increasing CNS noradrenaline levels alone is sufficient for efficacy, in part resulting from a lack of small molecules with sufficient selectivity. EXPERIMENTAL APPROACH: In this report, we present the in vitro pharmacological and in vivo pharmacokinetic and pharmacological properties of the novel, orally available and CNS penetrant inhibitor of the noradrenaline transporter (NET), WAY-318068 (1-[(1S,2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one). KEY RESULTS: WAY-318068 is a potent and effective inhibitor of the NET with a K(i) of 8.7 nM in a binding assay, and an IC(50) of 6.8 nM in an assay of transporter function, without significant binding to the dopamine transporter. Furthermore, the compound has only weak activity at the 5-HT transporter, leading to a functional selectivity of greater than 2500-fold. It is orally bioavailable with substantial quantities of the compound found in the CNS after oral dosing. As measured by microdialysis in rats, the compound causes a robust and significant increase in cortical noradrenaline levels without affecting 5-HT. WAY-318068 was effective in models of acute, visceral, inflammatory, osteoarthritic, neuropathic, diabetic and bone cancer pain, as well as in traditional models of depression at doses that do not cause motor deficits. CONCLUSIONS AND IMPLICATIONS: Collectively, the present results support the conclusion that selectively increasing CNS levels of noradrenaline is sufficient for efficacy in models of depression and pain.


Assuntos
Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/farmacologia , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Indóis/administração & dosagem , Indóis/farmacologia , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Medição da Dor/métodos , Administração Oral , Inibidores da Captação Adrenérgica/farmacocinética , Animais , Linhagem Celular Transformada , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Indóis/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos , Norepinefrina/metabolismo , Dor , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
20.
Xenobiotica ; 38(5): 540-58, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18421626

RESUMO

1. Prazosin, 2-[4-(2-furanoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline, is an antihypertensive agent that has been used safely since 1976 and is currently being investigated for the treatment of post-traumatic stress disorder. The in vivo metabolism of prazosin in rat was first reported in 1977, although at the time analytical techniques were not as sophisticated, nor were the mass spectrometers as sensitive, as today. Recently, the in vitro metabolism of prazosin in rat liver microsomes and cryopreserved hepatocytes was investigated using liquid chromatography/mass spectrometry (LC/MS), which revealed new metabolic pathways. 2. In the present work, rat in vivo metabolism was reinvestigated using a quadrupole time-of-flight mass spectrometer coupled with ultra-performance liquid chromatography, or chip-based nanoflow electrospray ionization, with the aim of identifying metabolites revealed by the in vitro studies and any new metabolites. 3. It is reported that prazosin was metabolized in rats to produce the metabolites observed in vitro. In addition, new phase I metabolites, M18, M20 and M21, were formed and conjugation with glucose or taurine formed the new phase II metabolites, M16 and M19, respectively. 4. Evidence for bioactivation of prazosin included detection of ring-opened metabolites (M4 and M7) and a cysteinyl-glycine conjugate (M17). Further support to the structure of the ring-opened metabolite M7 was obtained by nuclear magnetic resonance (NMR) experiments on M7 isolated from urine.


Assuntos
Anti-Hipertensivos/metabolismo , Prazosina/metabolismo , Animais , Anti-Hipertensivos/sangue , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/urina , Bile/metabolismo , Encéfalo/metabolismo , Cromatografia Líquida , Fezes/química , Espectroscopia de Ressonância Magnética , Masculino , Prazosina/sangue , Prazosina/farmacocinética , Prazosina/urina , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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