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1.
Sci Adv ; 10(23): eadk3081, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848367

RESUMO

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions in the liver's vasculature. We describe a thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) to protect islet redox status and function and to enable extrahepatic omentum islet engraftment. PPCN solution transitions from a liquid to a hydrogel at body temperature. Islets entrapped in PPCN and exposed to oxidative stress remain functional and support long-term euglycemia, in contrast to islets entrapped in a plasma-thrombin biologic scaffold. In the nonhuman primate (NHP) omentum, PPCN is well-tolerated and mostly resorbed without fibrosis at 3 months after implantation. In NHPs, autologous omentum islet transplantation using PPCN restores normoglycemia with minimal exogenous insulin requirements for >100 days. This preclinical study supports TP-IAT with PPCN in patients with CP and highlights antioxidant properties as a mechanism for islet function preservation.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Omento , Estresse Oxidativo , Transplante das Ilhotas Pancreáticas/métodos , Omento/metabolismo , Animais , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ácido Cítrico/farmacologia , Humanos , Antioxidantes/farmacologia , Pancreatite Crônica/metabolismo , Pancreatite Crônica/cirurgia , Pancreatite Crônica/patologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Masculino , Transição de Fase
2.
Artigo em Inglês | MEDLINE | ID: mdl-38414324

RESUMO

INTRODUCTION: Suicide is the third leading cause of death among US young adults, with significant racial/ethnic disparities related to the risk for suicide among Latine young adults. Despite the elevated risk for suicide, culturally relevant risk factors are not well-known. Intergenerational acculturative conflict (IAC) among Latine youth is a sociocultural factor associated with suicide ideation. METHOD: Although widely cited, the interpersonal theory of suicide (IPTS) lacks consistent support among Latine groups. The following cross-sectional study examined relationships between IAC categories (cultural preference, autonomy, and dating/staying out late), IPTS risk factors (i.e., thwarted belongingness and perceived burdensomeness), and suicide ideation frequency among 376 Mexican descent college students sampled using participant pools and snowball sampling (73.7% female: Mage = 19.88). RESULTS: Mediation analyses supported the hypotheses that IPTS risk factors partially explained the links between IAC categories and suicide ideation frequency. CONCLUSIONS: These findings advance our understanding of how sociocultural constructs, such as IAC, influence the IPTS and future advancements in culturally responsive treatments for suicide.

3.
Spiritual Clin Pract (Wash D C ) ; 10(3): 219-232, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37997582

RESUMO

Introduction: The suicide rate for individuals with schizophrenia spectrum disorders (SSDs) is over 20 times greater than that of the general population. Many people turn to religion in times of illness or stress. Religiosity is also deeply embedded into the culture, community life, and identity of many Latinx and Black/African American (B/AA) individuals. Religiosity has historically been associated with a lower risk of suicide. However, research also finds that, adaptive and maladaptive religious coping differentially impact mental health. Therefore, it is pertinent to examine religious coping's role on suicidality among Latinx and B/AA individuals with SSDs. Methods: This study examined relationships between adaptive and maladaptive religious coping, depression/anxiety, and suicidality among 91 Latinx and B/AA individuals with SSDs (M= 38.05 years old, SD = 11.92 years). Results: Maladaptive religious coping was positively associated with suicidality and was partially mediated through depression/anxiety. Moreover, adaptive religious coping moderated the relationship between maladaptive religious coping and depression/anxiety. Only when adaptive religious coping was at the mean observed level or below was maladaptive religious coping positively associated with depression/anxiety and suicidal ideation. Conclusion: Findings underscore the need to take religiosity into account when shaping therapies for Latinx and B/AA individuals with SSDs.

4.
Front Psychiatry ; 14: 1052454, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181867

RESUMO

Purpose: This study (a) documents the duration of untreated psychosis (DUP) and (b) examines both social and clinical correlates of DUP in a sample of U.S. Latinxs with first-episode psychosis (FEP). Methods: Data were collected for a longitudinal study evaluating a community education campaign to help primarily Spanish-speaking Latinxs recognize psychotic symptoms and reduce the DUP, or the delay to first prescribed antipsychotic medication after the onset of psychotic symptoms. Social and clinical variables were assessed at first treatment presentation. A sequential hierarchical regression was conducted using √DUP to identify independent predictors of the DUP. A structural equation model was used to explore the association between DUP predictors, DUP, and clinical and social correlates. Results: In a sample of 122 Latinxs with FEP, the median DUP was 39 weeks (M = 137.78, SD = 220.31; IQR = 160.39-5.57). For the full sample, being an immigrant and having self-reported relatively poor English-speaking proficiency and self-reported strong Spanish-speaking proficiency were related to a longer delay to first prescribed medication after psychosis onset. For the immigrant subgroup, being older at the time of migration was related to a longer delay. Self-reported English-speaking proficiency emerged as an independent predictor of the DUP. Although the DUP was not related to symptomatology, it was associated with poorer social functioning. Low self-reported English-speaking ability is associated with poorer social functioning via the DUP. Conclusion: Latinxs with limited English language skills are especially at high risk for experiencing prolonged delays to care and poor social functioning. Intervention efforts to reduce the delay in Latinx communities should pay particular attention to this subgroup.

5.
Psychiatry Res ; 313: 114639, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35597137

RESUMO

Individuals with psychotic spectrum disorders (PSDs) are at an increased risk for suicide compared to the general population. Both individuals with PSDs and communities of color are known to experience a high degree of mental health stigma. People of color also have strong family values that emphasize familial obligations and unity. The current study examined relationships between family cohesion, mental health self-stigma, and suicidal ideation among people of color with PSDs. The study sample consisted of 95 people of color with a PSD [Age in years: M = 38.27, SD=11.99; 65.3% male; 62.1% Latinx, 34.7% Black, 3.2% Other/Mixed]. Measures used were the suicidal ideation item from the BPRS interview, family cohesion subscale from the family environment scale, and three items asking participants about shame, guilt, or embarrassment experienced related to their PSD. In general, family cohesion was associated with less suicidal ideation, even when controlling for gender, education, and self-stigma. When examining conditional effects, family cohesion was associated with decreased suicidal ideation only when self-stigma was at or below the mean level observed. Additionally, self-stigma was associated with increased suicidal ideation only when family cohesion was above the mean level observed. Considering interactions between suicide risk and protective factors is paramount, as roles may shift.


Assuntos
Transtornos Psicóticos , Suicídio , Feminino , Humanos , Masculino , Transtornos Psicóticos/psicologia , Fatores de Risco , Pigmentação da Pele , Estigma Social , Ideação Suicida , Suicídio/psicologia
6.
Psychiatry Res ; 307: 114298, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34864231

RESUMO

Suicide is a leading cause of premature death in people with schizophrenia (Inoue et al., 2020). Hispanic/Latinx (H/L) individuals, the largest ethnic minority group in the U.S., face potential hurdles (e.g., discrimination, language barriers) when trying to receive care for psychotic spectrum disorders, which may increase their risk for suicidal ideation. Drawing from prior literature, we tested the hypotheses that greater acculturation and lower enculturation would be associated with increased suicidal ideation in a sample of 45 H/L individuals with psychotic spectrum disorders using a linear regression analysis controlling for gender and education. As hypothesized, greater acculturation and lower enculturation were associated with greater suicidal ideation. In line with prior research, results of this study suggest that maintaining beliefs and traditions from one's home culture may be beneficial to H/Ls with psychotic spectrum disorders and may reduce suicidal ideation whereas there may be detrimental aspects of mainstream United States culture on one's desire to live. Thus, encouraging H/L patients with psychotic spectrum disorders to maintain a sense of ethnic pride and stay engaged with practices and values from their culture of origin may help reduce suicidal ideation in this vulnerable population.


Assuntos
Transtornos Psicóticos , Ideação Suicida , Aculturação , Etnicidade , Hispânico ou Latino , Humanos , Grupos Minoritários , Transtornos Psicóticos/epidemiologia , Fatores de Risco , Estados Unidos
7.
J Ment Health ; 31(1): 14-21, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32662709

RESUMO

BACKGROUND: Schizophrenia is one of the most disabling disorders with the poorest outcomes. Cross-cultural research indicates an association between perceived racial discrimination and depression, anxiety, general psychological distress, and psychotic-spectrum disorders. Studies also find that coping moderates the relationship between discrimination and depression. Assessing subclinical symptoms may be useful in prevention efforts. AIMS: The study aims to (1) assess if perceived racial discrimination is associated with psychosis subclinical symptoms among a non-clinical sample and (2) examine the role of maladaptive coping and depression, anxiety, and stress. METHODS: The sample consisted of 261 ethnic minority undergraduate students. A structural equation model using a subclinical psychosis latent variable within a moderated mediation model assessed relationships between racial discrimination, maladaptive coping, depression, anxiety, and stress, and subclinical psychosis. RESULTS: Perceived racial discrimination was associated with greater subclinical symptoms of psychosis through increased depression, anxiety, and stress at greater levels of maladaptive coping. CONCLUSIONS: Knowing risk factors that can be targeted, such as perceived discrimination and maladaptive coping, may have implications for vulnerable populations.


Assuntos
Transtornos Psicóticos , Racismo , Adaptação Psicológica , Ansiedade , Depressão , Etnicidade , Humanos , Grupos Minoritários
8.
Nutrients ; 13(12)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34959806

RESUMO

Perceived changes in diet quality, emotional eating, physical activity, and lifestyle were evaluated in a group of Mexican adults before and during COVID-19 confinement. In this study, 8289 adults answered an online questionnaire between April and May 2020. Data about sociodemographic characteristics, self-reported weight and height, diet quality, emotional eating, physical activity, and lifestyle changes were collected. Before and after confinement, differences by sociodemographic characteristics were assessed with Wilcoxon, Anova, and linear regression analyses. Most participants were women (80%) between 18 and 38 years old (70%), with a low degree of marginalisation (82.8%) and a high educational level (84.2%); 53.1% had a normal weight and 31.4% were overweight. Half (46.8%) of the participants perceived a change in the quality of their diet. The Diet Quality Index (DQI) was higher during confinement (it improved by 3 points) in all groups, regardless of education level, marginalisation level, or place of residence (p < 0.001). Lifestyle changes were present among some of the participants, 6.1% stopped smoking, 12.1% stopped consuming alcohol, 53.3% sleep later, 9% became more sedentary, and increased their screen (43%) as well as sitting and lying down time (81.6%). Mexicans with Internet access staying at home during COVID-19 confinement perceived positive changes in the quality of their diet, smoking, and alcohol consumption, but negative changes in the level of physical activity and sleep quality. These results emphasise the relevance of encouraging healthy lifestyle behaviours during and after times of crisis to prevent the risk of complications due to infectious and chronic diseases.


Assuntos
COVID-19 , Comportamento Alimentar , Pandemias , Quarentena , SARS-CoV-2 , Comportamento Sedentário , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/prevenção & controle , Estudos Transversais , Feminino , Humanos , Acesso à Internet , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
Front Pharmacol ; 11: 246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256353

RESUMO

Plasmodium falciparum parasites are increasingly drug-resistant, requiring the search for novel antimalarials with distinct modes of action. Enzymes in the glutathione pathway, including glutathione S-transferase (GST), show promise as novel antimalarial targets. This study aims to better understand the biological function of Plasmodium GST, assess its potential as a drug target, and identify novel antiplasmodial compounds using the rodent model P. berghei. By using reverse genetics, we provided evidence that GST is essential for survival of P. berghei intra-erythrocytic stages and is a valid target for drug development. A structural model of the P. berghei glutathione S-transferase (PbGST) protein was generated and used in a structure-based screening of 900,000 compounds from the ChemBridge Hit2Lead library. Forty compounds were identified as potential inhibitors and analyzed in parasite in vitro drug susceptibility assays. One compound, CB-27, exhibited antiplasmodial activity with an EC50 of 0.5 µM toward P. berghei and 0.9 µM toward P. falciparum multidrug-resistant Dd2 clone B2 parasites. Moreover, CB-27 showed a concentration-dependent inhibition of the PbGST enzyme without inhibiting the human ortholog. A shape similarity screening using CB-27 as query resulted in the identification of 24 novel chemical scaffolds, with six of them showing antiplasmodial activity ranging from EC50 of 0.6-4.9 µM. Pharmacokinetic and toxicity predictions suggest that the lead compounds have drug-likeness properties. The antiplasmodial potency, the absence of hemolytic activity, and the predicted drug-likeness properties position these compounds for lead optimization and further development as antimalarials.

10.
Early Interv Psychiatry ; 14(5): 613-618, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31617322

RESUMO

AIM: Twitter is the most commonly used social media forum in public health and is considered the radio of the internet. Many health providers utilize this media to disseminate health information. Patient use of social media for mental health topics encourages providers to disseminate quality information and to develop virtual collaborative learning environments. This study explored trends in health information exchanged by patients, doctors and health organizations about schizophrenia through analyses of tweets posted using the #schizophrenia. METHODS: The likelihood that the information distributed by each user type was scholarly was assessed via qualitative and logistic regression analyses. Specifically, a sequential exploratory multimethod of data analysis guided this study with a sample of 981 tweets. RESULTS: Most tweets focused on the improvement of schizophrenia literacy (n = 366) followed by personal experiences/motivational stories (n = 207) and biological explanations of the disorder (n = 158). Logistic regression results indicated that compared to doctors, patients were less likely to tweet with a scholarly source (OR = 0.481, CI = 0.311, .744; P < .001). All users were less likely to include a scholarly source when tweeting about schizophrenia literacy, personal/motivational experiences, campaign/organizational events or illness management in comparison to those who tweeted about biological explanations of schizophrenia. CONCLUSION: Results suggest all users disseminated beneficial information that can increase public schizophrenia literacy and illness management, while connecting individuals to organizational events targeting this debilitating disorder. Health providers are encouraged to establish a presence on social media to share scholarly work with patients and promote prompt treatment for schizophrenia.


Assuntos
Troca de Informação em Saúde , Pessoal de Saúde/psicologia , Pessoas Mentalmente Doentes/psicologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Mídias Sociais , Estudos de Avaliação como Assunto , Feminino , Humanos , Disseminação de Informação , Funções Verossimilhança , Masculino , Educação de Pacientes como Assunto , Papel do Médico , Análise de Regressão
11.
Early Interv Psychiatry ; 13(6): 1389-1395, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30644163

RESUMO

AIM: Little is known about family processes and treatment seeking among Latinos with first-episode psychosis (FEP) living in the United States. This study examined family processes prior to treatment and their relation to duration of untreated psychosis (DUP) among Latinos with FEP and their family caregivers. METHODS: Thirty-three Latinos with FEP and their low-acculturated family caregivers (n = 33) participated in qualitative semi-structured interviews focused on treatment-seeking experience and family relationships. Transcripts were analysed using thematic analysis and themes were grouped based on short (n = 18) or long (n = 15) DUP. RESULTS: Findings revealed differences based on DUP length. Patients with short DUP had stronger family relationships characterized by open communication and disclosure of symptoms that facilitated awareness and direct action by family caregivers. However, patients with long DUP had more troubled family relationships that often challenged early treatment seeking. CONCLUSIONS: Findings highlight the relevance of family context in the provision of early treatment for Latinos with FEP. Family-based services are needed that increase awareness of symptoms and provide families with support that can facilitate ongoing patient treatment during this critical period.


Assuntos
Cuidadores/psicologia , Relações Familiares/psicologia , Hispânico ou Latino/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Transtornos Psicóticos/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Estados Unidos , Adulto Jovem
12.
Psychiatr Serv ; 69(11): 1153-1159, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30220245

RESUMO

OBJECTIVE: The study examined psychosis literacy among Latinos with first-episode psychosis (FEP) and their caregivers. The authors tested a model that knowledge of psychosis and attribution of illness to psychosis predicted professional help seeking in a cross-sectional design. METHODS: The sample (N=148) consisted of 79 Latino consumers who met criteria for a clinical diagnosis of a psychotic disorder and 69 family caregivers. Participants watched a four-minute narrative about a woman with psychosis and were asked to identify the symptoms of serious mental illness (knowledge of psychosis), describe the character's problem and whether she had a serious mental illness (illness attribution), and offer suggestions about what the parents should do (help seeking). Responses to the open-ended questions were reliably coded by two trained raters. RESULTS: Consumers reported low psychosis literacy across all indices (e.g., only 8% included delusions in their knowledge of serious mental illness). Compared with consumers, caregivers reported significantly greater psychosis literacy across most indices, although relatively few reported knowledge of delusions (28%) and disorganized speech (36%). Logistic regression analyses found that caregivers were more than twice as likely as consumers to suggest that the parents seek professional help. Among both consumers and caregivers, greater knowledge of psychosis and attribution of symptoms to serious mental illness were associated with increased likelihood of recommending professional help seeking. CONCLUSIONS: Community campaigns and psychoeducation interventions within clinical settings are needed to improve psychosis literacy among Latinos with FEP. Increasing knowledge of psychosis and facilitating attributions of psychotic symptoms to serious mental illness have the potential to promote professional help seeking.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde/etnologia , Letramento em Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adolescente , Adulto , Cuidadores , Estudos Transversais , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Adulto Jovem
13.
J Mol Diagn ; 20(4): 522-532, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29698836

RESUMO

Next-generation sequencing (NGS) diagnostic assays increasingly are becoming the standard of care in oncology practice. As the scale of an NGS laboratory grows, management of these assays requires organizing large amounts of information, including patient data, laboratory processes, genomic data, as well as variant interpretation and reporting. Although several Laboratory Information Systems and/or Laboratory Information Management Systems are commercially available, they may not meet all of the needs of a given laboratory, in addition to being frequently cost-prohibitive. Herein, we present the System for Informatics in the Molecular Pathology Laboratory (SIMPL), a free and open-source Laboratory Information System/Laboratory Information Management System for academic and nonprofit molecular pathology NGS laboratories, developed at the Genomic and Molecular Pathology Division at the University of Chicago Medicine. SIMPL was designed as a modular end-to-end information system to handle all stages of the NGS laboratory workload from test order to reporting. We describe the features of SIMPL, its clinical validation at University of Chicago Medicine, and its installation and testing within a different academic center laboratory (University of Colorado), and we propose a platform for future community co-development and interlaboratory data sharing.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Informática Médica/métodos , Patologia Molecular/métodos , Humanos , Reprodutibilidade dos Testes
14.
PLoS Pathog ; 12(7): e1005763, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27467575

RESUMO

A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.


Assuntos
Antimaláricos/uso terapêutico , Conjuntos de Dados como Assunto , Descoberta de Drogas/métodos , Malária/tratamento farmacológico , Doenças Negligenciadas/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Humanos , Bibliotecas de Moléculas Pequenas
15.
Mol Cancer Ther ; 14(11): 2497-507, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26358752

RESUMO

Ezrin is a member of the ERM (ezrin, radixin, moesin) family of proteins and functions as a linker between the plasma membrane and the actin cytoskeleton. Ezrin is a key driver of tumor progression and metastatic spread of osteosarcoma. We discovered a quinoline-based small molecule, NSC305787, that directly binds to ezrin and inhibits its functions in promoting invasive phenotype. NSC305787 possesses a very close structural similarity to commonly used quinoline-containing antimalarial drugs. On the basis of this similarity and of recent findings that ezrin has a likely role in the pathogenesis of malaria infection, we screened antimalarial compounds in an attempt to identify novel ezrin inhibitors with better efficacy and drug properties. Screening of Medicines for Malaria Venture (MMV) Malaria Box compounds for their ability to bind to recombinant ezrin protein yielded 12 primary hits with high selective binding activity. The specificity of the hits on ezrin function was confirmed by inhibition of the ezrin-mediated cell motility of osteosarcoma cells. Compounds were further tested for phenocopying the morphologic defects associated with ezrin suppression in zebrafish embryos as well as for inhibiting the lung metastasis of high ezrin-expressing osteosarcoma cells. The compound MMV667492 exhibited potent anti-ezrin activity in all biologic assays and had better physicochemical properties for drug-likeness than NSC305787. The drug-like compounds MMV020549 and MMV666069 also showed promising activities in functional assays. Thus, our study suggests further evaluation of antimalarial compounds as a novel class of antimetastatic agents for the treatment of metastatic osteosarcoma.


Assuntos
Adamantano/análogos & derivados , Antineoplásicos/farmacologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Osteossarcoma/tratamento farmacológico , Quinolinas/farmacologia , Adamantano/farmacologia , Animais , Antimaláricos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Immunoblotting , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos BALB C , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Bibliotecas de Moléculas Pequenas/farmacologia , Ressonância de Plasmônio de Superfície , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
16.
Malar J ; 13: 313, 2014 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-25115675

RESUMO

BACKGROUND: Subtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2-immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts. METHODS: Swiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on parasite development, infected mice were evaluated by blood film and Giemsa staining. In addition, collected immune sera were used to perform passive immunization experiments in non-immunized, P. berghei-infected mice to determine the potential role of SUB2 in parasite development in the mosquito. RESULTS: Following P. berghei challenge, SUB2-immunized mice develop a lower parasitaemia and show improved survival when compared to control immunized mice. Moreover, SUB2 immunization results in an increase in the number of multiply invaded red blood cells, suggesting that SUB2 antibodies interfere with merozoite invasion. Passive immunization experiments imply that SUB2 may not have a major role in ookinete invasion, but this requires further investigation. CONCLUSION: By interfering with red blood cell invasion, immunization against SUB2 limits malaria parasite development and confers protection from severe malaria. Together, these results provide proof-of-principle evidence for future investigation into the use of SUB2 as a vaccine or drug target to interrupt parasite development in more relevant human malaria models.


Assuntos
Eritrócitos/parasitologia , Vacinas Antimaláricas/imunologia , Malária/imunologia , Merozoítos/imunologia , Plasmodium berghei/imunologia , Sequência de Aminoácidos , Animais , Feminino , Malária/prevenção & controle , Vacinas Antimaláricas/química , Camundongos , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Subtilisina , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia
17.
PLoS One ; 9(3): e92457, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24658545

RESUMO

Human Interleukin-3 (IL-3) is a lymphokine member of a class of transiently expressed mRNAs harboring Adenosine/Uridine-Rich Elements (ARE) in their 3' untranslated regions (3'-UTRs). The regulatory effects of AREs are often mediated by specific ARE-binding proteins (ARE-BPs). In this report, we show that the human IL-3 3'-UTR plays a post-transcriptional regulation role in two human transformed cell lines. More specifically, we demonstrate that the hIL-3 3'-UTR represses the translation of a luciferase reporter both in HeLa and Jurkat T-cells. These results also revealed that the hIL-3 3'-UTR-mediated translational repression is exerted by an 83 nt region comprised mainly by AREs and some non-ARE sequences. Moreover, electrophoretic mobility shift assays (EMSAs) and UV-crosslinking analysis show that this hIL-3 ARE-rich region recruits five specific protein complexes, including the ARE-BPs HuR and TIA-1. HuR binding to this ARE-rich region appears to be spatially modulated during T-cell activation. Together, these results suggest that HuR recognizes the ARE-rich region and plays a role in the IL-3 3'-UTR-mediated post-transcriptional control in T-cells.


Assuntos
Regiões 3' não Traduzidas , Proteínas ELAV/fisiologia , Interleucina-3/genética , Interleucina-3/metabolismo , Proteínas de Ligação a RNA/fisiologia , Proteína Semelhante a ELAV 1 , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Células Jurkat , Ativação Linfocitária , Proteínas de Ligação a Poli(A)/fisiologia , Antígeno-1 Intracelular de Células T , Transformação Genética
18.
Rev. Fac. Med. UNAM ; 54(6): 4-8, nov.-dic. 2011. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-956898

RESUMO

Introducción: La cetoacidosis diabética (CAD) es una complicación metabòlica aguda que afecta a los pacientes diabéticos. Las anormalidades metabólicas propias de la CAD favorecen el incremento de los niveles de lipasa y amilasa, así como la formación de cuerpos cetónicos, lo que empeora el estado de acidosis y el desequilibrio hídroelectrolítico. Estas alteraciones, aunadas a las manifestaciones clínicas asociadas a la CAD, son fuente de interpretación errónea con cuadros de abdomen agudo. Aunque no se conoce un significado clínico claro, los niveles de hiperlipasemia parecen variar en función de la severidad de la CAD, por lo que en el presente estudio exploramos esta posible correlación. Material y métodos: Estudio observacional con diseño transversal analítico y comparativo, que incluyó a pacientes de medicina interna en los hospitales generales de Xoco, Balbuena y Ticomán, de la Secretaría de Salud del Distrito Federal, con diagnóstico de CAD, distintos niveles de lipasa y en ausencia de pancreatitis aguda, patología gástrica o de glándula parótida. El grado de severidad de CAD se determinó con base en la información del expediente clínico. Se consideró hiperlipasemia con un valor de lipasa > 38 Ul/l). Resultados: Se incluyó a 45 pacientes con CAD, de los que se excluyó a 4. Los 41 pacientes estudiados, se dividieron en 3 grupos de acuerdo a la severidad de la CAD. La prevalencia general de hiperlipasemia fue de 51.2%, con una distribución de 42.8, 33.3 y 23.9%, entre la población con CAD leve, moderada y severa, respectivamente. Se encontró que los niveles de lipasa de los grupos de CAD leve y severa eran distintos, pero no hubo diferencia al considerar únicamente la población que mostró hiperlipasemia. Se encontró una correlación inversa, aunque baja, entre la severidad de CAD y los niveles de lipasa sérica (r = -0.37, IC del 95%, -0.07 a -0.6; p = 0.01), así como una relación de la lipasa con el pH (r = 0.3), el HCO3 (r = 0.3) y la brecha aniónica (r = -0.23), de acuerdo al análisis de regresión múltiple. Este estudio sugiere que la presencia de hiperlipasemia carece de valor como marcador de severidad de la CAD. Conclusión: Existe una tendencia a la relación inversa entre los niveles lipasa y la severidad de la CAD, que a la luz del conocimiento actual no se puede dar un valor significativo para la interpretación clínica.


Introduction: Diabetic ketoacidosis (DKA) is an acute metabolic complication which affects diabetic patients. DKA metabolic abnormalities promote the increase of lipase and amylase serum levels, as well as the overproduction of ketone bodies, worsening the acidosis state and hydroelectrolytic balance. These abnormalities, together with the clinical features associated with DKA are potential sources for misinterpreting the symptoms as acute abdomen. Although the clinical meaning is unclear, hyperlipasemia levels seem to vary according to the severity of DKA; hence, this likely correlation is assessed in this study. Material and methods: Observational cross-sectional analytic comparative study, including internal medicine patients from the following general hospitals: Xoco, Balbuena and Ticomán (SSDF). The patients were diagnosed with DKA, showing different lipase levels with no acute pancreatitis, gastric and/or parotid gland pathology. The severity of DKA was assessed based on the clinical record. Hyperlipasemia was considered as a lipase serum level of >38 UI/L. Results: Forty-five patients with DKA were included and 4 were excluded. The 41 patients studied were divided in 3 groups according to their DKA severity. The general prevalence of hyperlipasemia was 51.2%, with a distribution of 42.8%, 33.3% and 23.9% among patients with mild, moderate and severe DKA, respectively. Lipase levels between the groups with mild and severe DKA were different; however, no difference was found when comparing only patients showing hyperlipasemia. Furthermore, a low inverse correlation was found between DKA severity and serum lipase levels (r=0.37), HCO3 (r=0.3) and anion gap (r=0.23), according to multiple regression analysis. This study suggests that the presence of hyperlipasemia is not a good marker to indicate the severity of DKA. Conclusion: Lipase levels and DKA severity show an inverse correlation, which, according to current knowledge, should have no significant value for clinical interpretation.

19.
Lima; Perú. Ministerio de Salud. Instituto Nacional de Salud. Centro Nacional de Alimentación y Nutrición; 1 ed; 2010. 27 p. tab, graf.
Monografia em Espanhol | LILACS, MINSAPERU | ID: biblio-1182176

RESUMO

La presente publicación establece las pautas que orientan al personal de salud durante el cálculo teórico de la ración del programa del vaso de leche a fin de que los alimentos que se adquieran y distribuyan en dicho programa, cumplan con los valores nutricionales mínimos establecidos


Assuntos
Educação Alimentar e Nutricional , Estado Nutricional , Política Nutricional , Programas de Nutrição
20.
Rev. cuba. farm ; 36(2): 107-111, mayo-ago. 2002. tab, graf
Artigo em Espanhol, Inglês | LILACS | ID: lil-340506

RESUMO

Se informan los resultados obtenidos del estudio del contenido de alcaloides en las hojas y tallos de la especie endémica cubana Annona sclerophylla, de discreta actividad antimicrobiana. Para la extracción y purificación de dichos metabolitos se utilizaron solventes orgánicos y métodos cromatográficos de separación por columna. Con el empleo de técnicas espectroscópicas de UV, IR, masa y RMN1H y 13C, así como por la medición de sus constantes físicas, se identificaron los alcaloides isocorypalmina y liriodenina, y los compuestos (-)-kau-16-en-19-oico y (-)-kauran-16a-o1


Assuntos
Alcaloides , Extratos Vegetais , Plantas Medicinais
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