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1.
BMC Health Serv Res ; 24(1): 186, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336716

RESUMO

BACKGROUND: For adults living with HIV (ALHIV) and comorbidities, access to comprehensive healthcare services is crucial to achieving optimal health outcomes. This study aims to describe lived experiences, challenges, and coping strategies for accessing care for hypertension and/or diabetes (HTN/DM) in HIV care and treatment clinics (CTCs) and other healthcare settings. METHODOLOGY: We conducted a qualitative study that employed a phenomenological approach between January and April 2022 using a semi-structured interview guide in six HIV CTCs in Dar es Salaam, Tanzania. We purposively recruited 33 ALHIV with HTN (n = 16), DM (n = 10), and both (n = 7). Thematic content analysis was guided by the 5As framework of access to care. FINDINGS: The majority of the participants were females, between the ages of 54-73, and were recruited from regional referral hospitals. HIV CTCs at regional referral hospitals had more consistent provision of HTN screening services compared to those from district hospitals and health centers. Participants sought HTN/DM care at non-CTC health facilities due to the limited availability of such services at HIV CTCs. However, healthcare delivery for these conditions was perceived as unaccommodating and poorly coordinated. The need to attend multiple clinic appointments for the management of HTN/DM in addition to HIV care was perceived as frustrating, time-consuming, and financially burdensome. High costs of care and transportation, limited understanding of comorbidities, and the perceived complexity of HTN/DM care contributed to HTN/DM treatment discontinuity. As a means of coping, participants frequently monitored their own HTN/DM symptoms at home and utilized community pharmacies and dispensaries near their residences to check blood pressure and sugar levels and obtain medications. Participants expressed a preference for non-pharmaceutical approaches to comorbidity management such as lifestyle modification (preferred by young participants) and herbal therapies (preferred by older participants) because of concerns about side effects and perceived ineffectiveness of HTN/DM medications. Participants also preferred integrated care and focused patient education on multimorbidity management at HIV CTCs. CONCLUSION: Our findings highlight significant barriers to accessing HTN/DM care among ALHIV, mostly related to affordability, availability, and accessibility. Integration of NCD care into HIV CTCs, could greatly improve ALHIV health access and outcomes and align with patient preference.


Assuntos
Diabetes Mellitus , Infecções por HIV , Hipertensão , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Infecções por HIV/diagnóstico , Tanzânia/epidemiologia , Diabetes Mellitus/terapia , Diabetes Mellitus/tratamento farmacológico , Hipertensão/terapia , Hipertensão/tratamento farmacológico , Comorbidade
2.
BMC Med Educ ; 22(1): 28, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012538

RESUMO

BACKGROUND: Funded grant proposals provide biomedical researchers with the resources needed to build their research programs, support trainees, and advance public health. Studies using National Institutes of Health (NIH) data have found that investigators from underrepresented groups in the biomedical workforce are awarded NIH research grants at disproportionately lower rates. Grant writing training initiatives are available, but there is a dearth of rigorous research to determine the effectiveness of such interventions and to discern their essential features. METHODS: This 2 × 2, unblinded, group-randomized study compares the effectiveness of variations of an NIH-focused, grant writing, group coaching intervention for biomedical postdoctoral fellows and early-career faculty. The key study outcomes are proposal submission rates and funding rates. Participants, drawn from across the United States, are enrolled as dyads with a self-selected scientific advisor in their content area, then placed into coaching groups led by senior NIH-funded investigators who are trained in the intervention's coaching practices. Target enrollment is 72 coaching groups of 4-5 dyads each. Groups are randomized to one of four intervention arms that differ on two factors: [1] duration of coaching support (regular dose = 5 months of group coaching, versus extended dose = regular dose plus an additional 18 months of one-on-one coaching); and [2] mode of engaging scientific advisors with the regular dose group coaching process (unstructured versus structured engagement). Intervention variations were informed by programs previously offered by the NIH National Research Mentoring Network. Participant data are collected via written surveys (baseline and 6, 12, 18, and 24 months after start of the regular dose) and semi-structured interviews (end of regular dose and 24 months). Quantitative analyses will be intention-to-treat, using a 2-sided test of equality of the effects of each factor. An inductive, constant comparison analysis of interview transcripts will be used to identify contextual factors -- associated with individual participants, their engagement with the coaching intervention, and their institutional setting - that influence intervention effectiveness. DISCUSSION: Results of this study will provide an empirical basis for a readily translatable coaching approach to supporting the essential grant writing activities of faculty, fellows, and other research trainees, including those from underrepresented groups.


Assuntos
Pesquisa Biomédica , Tutoria , Humanos , Mentores , Pesquisadores , Estados Unidos , Recursos Humanos
3.
Glob Chang Biol ; 25(3): 1032-1048, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548757

RESUMO

The European Union (EU) has recently published its first list of invasive alien species (IAS) of EU concern to which current legislation must apply. The list comprises species known to pose great threats to biodiversity and needs to be maintained and updated. Horizon scanning is seen as critical to identify the most threatening potential IAS that do not yet occur in Europe to be subsequently risk assessed for future listing. Accordingly, we present a systematic consensus horizon scanning procedure to derive a ranked list of potential IAS likely to arrive, establish, spread and have an impact on biodiversity in the region over the next decade. The approach is unique in the continental scale examined, the breadth of taxonomic groups and environments considered, and the methods and data sources used. International experts were brought together to address five broad thematic groups of potential IAS. For each thematic group the experts first independently assembled lists of potential IAS not yet established in the EU but potentially threatening biodiversity if introduced. Experts were asked to score the species within their thematic group for their separate likelihoods of i) arrival, ii) establishment, iii) spread, and iv) magnitude of the potential negative impact on biodiversity within the EU. Experts then convened for a 2-day workshop applying consensus methods to compile a ranked list of potential IAS. From an initial working list of 329 species, a list of 66 species not yet established in the EU that were considered to be very high (8 species), high (40 species) or medium (18 species) risk species was derived. Here, we present these species highlighting the potential negative impacts and the most likely biogeographic regions to be affected by these potential IAS.


Assuntos
Biodiversidade , Ecossistema , Espécies Introduzidas/tendências , Animais , Conferências de Consenso como Assunto , Política Ambiental , União Europeia , Espécies Introduzidas/estatística & dados numéricos , Medição de Risco
4.
J Gen Intern Med ; 34(3): 356-362, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30003480

RESUMO

BACKGROUND: In response to the landmark report "Beyond Bias and Barriers: Fulfilling the Potential of Women in Academic Science and Engineering," the NIH Office of Research on Women's Health issued a request for applications that funded 14 R01 grants to investigate causal factors to career success for women in STEM. Following completion of the 4-year grants, the grant PIs formed a grassroots collaborative, the Research Partnership on Women in Science Careers. OBJECTIVE: To summarize the work of the Research Partnership, which resulted in over 100 publications. METHODS: We developed six themes to organize the publications, with a "Best Practices" for each theme at the end of each section: Barriers to Career Advancement; Mentoring, Coaching, and Sponsorship; Career Flexibility and Work-Life Balance; Pathways to Leadership; Compensation Equity; and Advocating for Change and Stakeholder Engagement. RESULTS: Women still contend with sexual harassment, stereotype threat, a disproportionate burden of family responsibilities, a lack of parity in compensation and resource allocation, and implicit bias. Strategies to address these barriers using the Bronfenbrenner ecological model at the individual, interpersonal, institutional, academic community, and policy levels include effective mentoring and coaching, having a strong publication record, addressing prescriptive gender norms, positive counter-stereotype imaging, career development training, networking, and external career programs such as the AAMC Early and Mid-Career Programs and Executive Leadership in Academic Medicine (ELAM). CONCLUSIONS: Cultural transformation is needed to address the barriers to career advancement for women. Implementing the best practices noted of the work of the Research Partnership can help to achieve this goal.


Assuntos
Mobilidade Ocupacional , Docentes de Medicina/tendências , Pessoal de Laboratório/tendências , Relatório de Pesquisa/tendências , Sexismo/tendências , Carga de Trabalho , Docentes de Medicina/psicologia , Feminino , Humanos , Pessoal de Laboratório/psicologia , Sexismo/prevenção & controle , Sexismo/psicologia , Carga de Trabalho/psicologia
6.
J Hist Behav Sci ; 51(4): 387-408, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26334552

RESUMO

This article examines the evolving connections between local conditions and knowledge processes in women's and gender studies, a research field in the social sciences and humanities. Data are historical records from five early-adopting women's and gender studies units in the United States and interviews with affiliated professors. In their formative years, these programs were consistent in their intellectual content. Scholars across sites defined the purpose of women's studies similarly: to address the lack of research on women and social problems of sex inequality. Gradually, scholars incorporated a range of analytic categories into women's studies' agenda, including gender identities and masculinities, leading to diverse understandings and redefinitions of the central objects of analysis. Analytic shifts are reflected in differences in the institutional and intellectual composition of programs and departments. To explain how local departmental conditions affect the conception of core objects of study in gender research, the author builds on the literature on knowledge ecologies and introduces the concept of the "supple object."


Assuntos
Identidade de Gênero , Universidades/história , Mulheres , Feminino , História do Século XX , História do Século XXI , Ciências Humanas/educação , Humanos , Conhecimento , Masculino , Ciências Sociais/educação , Estados Unidos , Universidades/organização & administração
8.
J Lesbian Stud ; 18(4): 372-92, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25298099

RESUMO

In mid-century popular presses published paperbacks about lesbians, gay men, and characters with male and female lovers.  Barbara Grier was the first to catalog novels featuring lesbian subplots by classifying stories based on the extent and style of lesbian content.  I perform a content analysis of 49 novels, motivated by these questions:  How did novels with lesbian and gay characters differ from heterosexual romances?  What do differences reveal about cultural understandings of love, gender, and sexuality?  I find uniformity in the structural logic of novels.  However, there are different narrative strategies, and protagonists' gender and sexuality predict a novel's trajectory.


Assuntos
Feminismo/história , Homossexualidade Feminina/história , Literatura Moderna/história , Publicações Periódicas como Assunto/história , Direitos da Mulher/história , Literatura Erótica , Feminino , História do Século XX , Humanos , Amor , Masculino , Estados Unidos
9.
BMC Ecol Evol ; 24(1): 21, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347459

RESUMO

BACKGROUND: The origin of variation is of central interest in evolutionary biology. Maternal mRNAs govern early embryogenesis in many animal species, and we investigated the possibility that heterogeneity in maternal mRNA provisioning of eggs can be modulated by environmental stimuli. RESULTS: We employed two sibling species of the ascidian Ciona, called here types A and B, that are adapted to different temperature regimes and can be hybridized. Previous study showed that hybrids using type B eggs had higher susceptibility to thermal stress than hybrids using type A eggs. We conducted transcriptome analyses of multiple single eggs from crosses using eggs of the different species to compare the effects of maternal thermal stress on heterogeneity in egg provisioning, and followed the effects across generations. We found overall decreases of heterogeneity of egg maternal mRNAs associated with maternal thermal stress. When the eggs produced by the F1 AB generation were crossed with type B sperm and the progeny ('ABB' generation) reared unstressed until maturation, the overall heterogeneity of the eggs produced was greater in a clutch from an individual with a heat-stressed mother compared to one from a non-heat-stressed mother. By examining individual genes, we found no consistent overall effect of thermal stress on heterogeneity of expression in genes involved in developmental buffering. In contrast, heterogeneity of expression in signaling molecules was directly affected by thermal stress. CONCLUSIONS: Due to the absence of batch replicates and variation in the number of reads obtained, our conclusions are very limited. However, contrary to the predictions of bet-hedging, the results suggest that maternal thermal stress at the embryo stage is associated with reduced heterogeneity of maternal mRNA provision in the eggs subsequently produced by the stressed individual, but there is then a large increase in heterogeneity in eggs of the next generation, although itself unstressed. Despite its limitations, our study presents a proof of concept, identifying a model system, experimental approach and analytical techniques capable of providing a significant advance in understanding the impact of maternal environment on developmental heterogeneity.


Assuntos
RNA Mensageiro Estocado , Sêmen , Animais , Feminino , Masculino , Humanos , RNA Mensageiro Estocado/genética , Perfilação da Expressão Gênica , Mães , Evolução Biológica
10.
Meth Psychol ; 102024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38586561

RESUMO

This paper demonstrates how Longitudinal Qualitative Research (LQR) is an innovative method to understand the lived experiences of members of minoritized groups when temporality is a structuring element of their experiences. Most qualitative research in psychology is cross-sectional, which limits our understanding of individuals whose experiences are context-dependent and linked to the temporal norms of specific social environments. LQR is unique for allowing researchers to compare change and stability over time and reveal how social challenges and barriers impact perspective shifts and long-term decision-making. To demonstrate the usefulness of LQR as an inclusive methodology, we discuss an ongoing study of career decision-making among a diverse cohort of biomedical scientists. We have used annual interviews to follow biomedical science trainees from the beginning of their PhD into the initial stages of their careers. We present case studies of minoritized scientists to illustrate the methods for long-term engagement used to elicit sensitive and critical information during their training. We show how LQR is a viable methodology for a variety of research questions and can be accomplished using large or small sample sizes and limited resources. Our primary goal is to show how LQR is useful to understand the experiences of minoritized individuals in contexts that have historically excluded them.

11.
J Community Health ; 38(1): 113-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22772956

RESUMO

The present study was part of a larger randomized controlled childhood obesity prevention trial based in 11 public recreation centers. The primary aim was to evaluate the effectiveness of a multi-level intervention to prevent the onset of overweight and obesity among children (5-8 years of age). However, the purpose of the current study was to identify sociodemographic variables, such as acculturation, that were associated with receipt of physician advice among Latino primary caregivers. Participants included 221 Latino primary caregivers and their children from San Diego, CA. Cross-sectional baseline data suggested that Latino children with private insurance were more likely to receive physician advice regarding their eating habits. Conversely, primary caregivers between the ages of 30-39 were less likely to receive physician advice regarding their child's eating habits. Current findings highlight the continued need to improve preventive efforts and reduce health disparities among a vulnerable population, such as Latinos.


Assuntos
Aculturação , Cuidadores/educação , Comportamentos Relacionados com a Saúde/etnologia , Hispânico ou Latino/psicologia , Relações Médico-Paciente , Adolescente , Adulto , Cuidadores/psicologia , Criança , Pré-Escolar , Comunicação , Estudos Transversais , Comportamento Alimentar , Feminino , Promoção da Saúde , Hispânico ou Latino/estatística & dados numéricos , Humanos , Seguro Saúde/estatística & dados numéricos , Masculino , Obesidade/prevenção & controle , Adulto Jovem
12.
Wellcome Open Res ; 8: 583, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38779044

RESUMO

We present a genome assembly from an individual Ascidia mentula (the (a solitary sea squirt); Chordata; Ascidiacea; Phlebobranchia; Ascidiidae). The genome sequence is 197.0 megabases in span. Most of the assembly is scaffolded into 9 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 19.46 kilobases in length.

13.
Wellcome Open Res ; 8: 26, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251659

RESUMO

We present a genome assembly from a Bugulina stolonifera colony (an erect bryozoan; Bryozoa; Gymnolaemata; Cheilostomatida; Bugulidae). The genome sequence is 235 megabases in span. Most of the assembly (99.85%) is scaffolded into 11 chromosomal pseudomolecules. The mitochondrial genome was also assembled and is 14.4 kilobases long.

14.
J Acquir Immune Defic Syndr ; 94(2S): S73-S79, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707852

RESUMO

BACKGROUND: There is an urgent need to conduct innovative research on the health needs of populations whose intersecting identities, such as being Black, Indigenous, and other People of Color (BIPOC) and sexual and gender identity (SGM) persons, put them at greater risk of HIV infection. More so, as important as it is to train on the best practices, it is as important to train aspiring BIPOC SGM scholars in intersectional HIV science so that they can address the HIV-related issues of BIPOC SGM populations. METHODS: In line with guidelines to increase diversity in the HIV workforce, we sought to (1) solidify the interest of BIPOC SGM trainees engaging in intersectional HIV science by piloting a 2-week Summer Intensive Program, (2) leverage the relationships and resources of our community partner to enhance our recruitment from HBCUs and MSIs, and (3) identify opportunities for postprogram training and mentoring activities. RESULTS: Our data suggest that participants gained a great deal from the instructional sessions. Participants commented on the quality of the sessions, effectiveness of the instructional faculty, and a confirmed interest in HIV science. CONCLUSIONS: We succeeded in promoting interest in and commitment to HIV science among early career BIPOC SGM scholars. An instructional program of this intensity is best suited to those with some experience in graduate school and existing interest in HIV science. As a program serving multiply minoritized populations, clarification of host institution policies and procedures, as well as administrative support, are essential for ensuring a smooth experience for scholars visiting from outside institutions.


Assuntos
Identidade de Gênero , Infecções por HIV , Feminino , Humanos , Masculino , Infecções por HIV/prevenção & controle , Comportamento Sexual , Negro ou Afro-Americano , Grupos Minoritários , Povos Indígenas , Pesquisa Biomédica
15.
Wellcome Open Res ; 8: 38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363061

RESUMO

We present a genome assembly from an adult colony of Membranipora membranacea (the sea mat; Bryozoa; Gymnolaemata; Cheilostomatida; Membraniporidae). The genome sequence is 339 megabases in span. Most of the assembly (99.95%) is scaffolded into 11 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 14.7 kilobases in length.

16.
Wellcome Open Res ; 8: 543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38404634

RESUMO

We present a genome assembly from an individual Clavelina lepadiformis (the light-bulb sea squirt; Chordata; Ascidiacea; Aplousobranchia; Clavelinidae). The genome sequence is 210.1 megabases in span. Most of the assembly is scaffolded into 9 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 14.48 kilobases in length.

17.
PLOS Glob Public Health ; 3(4): e0001024, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37027354

RESUMO

While viral load (VL) testing is critical to effective treatment of human immunodeficiency virus (HIV), little is known about patients' experiences with, and barriers to VL-testing in the context of HIV infection. We assessed patient reported experience measures (PREMs) on VL-testing in public HIV clinics in Tanzania. In a cross-sectional convergent mixed method study, we collected information on VL test related PREMs, clinical and sociodemographic factors. PREMs were measured using a 5-point Likert scale. Focus Group Discussions (FGDs) explored on experience, access, and barriers to VL-testing. Descriptive statistics summarized patients' factors and PREMs. Logistic regression was used to explore association of patient factors, PREMs and satisfaction with VL-testing services. Thematic analysis was used for qualitative data. A total of 439 (96.48%) respondents completed the survey, 331 (75.40%) were female, median (IQR) age was 41(34, 49) years. A total of 253(57.63%) had a VL test at least once in the past 12 months, of whom 242(96.0%) had VL<1000 copies/ml. Investigating barriers to VL-testing, most participants (>92.0%) reported good or very good health services responsiveness (HSR). A scale of very good was chosen by the majority for being treated with respect 174(39.6%), listened to 173(39.4%), following advice 109(24.8%), being involved in decisions 101(23.0%), and for communication 102(23.3%). Satisfaction on VL-testing services was significantly associated with respondents following care providers' advice, (aOR) = 2.07 [95%CI 1.13-3.78], involvement in decisions aOR = 4.16 [95%CI 2.26-7.66], and communication aOR = 2.27 [95%CI 1.25-4.14]. FGDs findings converged with the survey data, with identified barriers to VL test including lack of autonomy in decision making, little awareness on the benefits of the test, long waiting time, stigma, competing priorities for those with comorbidities and transport costs. Satisfaction on VL-testing was largely a result of involvement in decision making, following care provider's advice and good communication; entities needing universal improvement across the country.

18.
J Acquir Immune Defic Syndr ; 94(2S): S13-S20, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707843

RESUMO

BACKGROUND: The Centers for AIDS Research Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) aims to establish programs to develop pathways for successful careers in HIV science among scholars from underrepresented racial and ethnic populations. This article describes cross-site evaluation outcomes during the first 18 months (July 2021-December 2022) across 15 programs. METHODS: The aims of the evaluation were to characterize participants, describe feasibility, challenges, and successes of the programs and provide a basis for the generalizability of best practices to Diversity, Equity, and Inclusion (DEI) programs in the United States. Two primary data collection methods were used: a quarterly programmatic monitoring process and a centrally managed, individual-level, participant quantitative and qualitative survey. RESULTS: During the first year of evaluation data collection, 1085 racially and ethnically diverse scholars ranging from the high school to postdoctoral levels applied for CDEIPI programs throughout the United States. Of these, 257 (23.7%) were selected to participate based on program capacity and applicant qualifications. Participants were trained by 149 mentors, teachers, and staff. Of the N = 95 participants responding to the individual-level survey, 95.7% agreed or strongly agreed with statements of satisfaction with the program, 96.8% planned to pursue further education, and 73.7% attributed increased interest in a variety of HIV science topics to the program. Qualitative findings suggest strong associations between mentorship, exposure to scientific content, and positive outcomes. CONCLUSIONS: These data provide evidence to support the feasibility and impact of novel DEI programs in HIV research to engage and encourage racially and ethnically diverse scholars to pursue careers in HIV science.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Grupos Minoritários , Etnicidade , Minorias Étnicas e Raciais , Diversidade, Equidade, Inclusão , Estudantes
19.
J Acquir Immune Defic Syndr ; 94(2S): S5-S12, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707842

RESUMO

BACKGROUND: There is an urgent need to increase diversity among scientific investigators in the HIV research field to be more reflective of communities highly affected by the HIV epidemic. Thus, it is critical to promote the inclusion and advancement of early-stage scholars from racial and ethnic groups underrepresented in HIV science and medicine. METHODS: To widen the HIV research career pathway for early-stage scholars from underrepresented minority groups, the National Institutes of Health supported the development of the Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI). This program was created through partnerships between CFARs and Historically Black Colleges and Universities and other Minority Serving Institutions throughout the United States. RESULTS: Seventeen CFARs and more than 20 Historically Black Colleges and Universities and Minority Serving Institutions have participated in this initiative to date. Programs were designed for the high school (8), undergraduate (13), post baccalaureate (2), graduate (12), and postdoctoral (4) levels. Various pedagogical approaches were used including didactic seminar series, intensive multiday workshops, summer residential programs, and mentored research internship opportunities. During the first 18 months of the initiative, 257 student scholars participated in CDEIPI programs including 150 high school, 73 undergraduate, 3 post baccalaureate, 27 graduate, and 4 postdoctoral students. CONCLUSION: Numerous student scholars from a wide range of educational levels, geographic backgrounds, and racial and ethnic minority groups have engaged in CDEIPI programs. Timely and comprehensive program evaluation data will be critical to support a long-term commitment to this unique training initiative.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Estados Unidos , Humanos , Etnicidade , Diversidade, Equidade, Inclusão , Grupos Minoritários
20.
Bioorg Med Chem Lett ; 22(12): 3895-9, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22608963

RESUMO

A novel N-aryl piperazine-1-carboxamide series of human CCR2 chemokine receptor antagonists was discovered. Early analogues were potent at CCR2 but also inhibited the hERG cardiac ion channel. Structural modifications which decreased lipophilicity and basicity resulted in the identification of a sub-series with an improved margin over hERG. The pharmacological and pharmacokinetic properties of the lead compound from this series, N-(3,4-dichlorophenyl)-4-[(2R)-4-isopropylpiperazine-2-carbonyl]piperazine-1-carboxamide, are described.


Assuntos
Anti-Inflamatórios/síntese química , Piperazinas/síntese química , Receptores CCR2/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Cálcio/metabolismo , Cães , Desenho de Fármacos , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Inflamação/tratamento farmacológico , Piperazinas/farmacocinética , Piperazinas/farmacologia , Ligação Proteica , Ratos , Receptores CCR2/metabolismo
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