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1.
Rev Esp Enferm Dig ; 115(6): 341-342, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36975156

RESUMO

Neuroendocrine tumors (NETs) are rare, with an annual incidence of 10/100,000 inhabitants, with an increase in incidence in the last 30 years that probably is due to an improvement in diagnostic techniques. However, NETs the second neoplasia most prevalent advanced disease of the gastrointestinal tract due to its high survival. It´s way of presentation is usually with vague symptoms and often without an incidental diagnosis from the use of imaging techniques. A correct differential diagnosis will allow us its early diagnosis and its treatment. We present the case of a patient diagnosed with NET whose symptoms of presentation was lower gastrointestinal bleeding with a negative endoscopic study.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Intestinais/complicações , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/patologia , Hemorragia Gastrointestinal/etiologia , Intestino Delgado/patologia
2.
BMC Cancer ; 21(1): 580, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016080

RESUMO

BACKGROUND: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. METHODS: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. RESULTS: Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3-20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0-11). CONCLUSIONS: Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.


Assuntos
Aminoácidos/administração & dosagem , Diarreia/tratamento farmacológico , Tumores Neuroendócrinos/complicações , Soluções para Reidratação/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diarreia/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
3.
Nutr Health ; 27(4): 461-465, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33583247

RESUMO

BACKGROUND: A historical turning point occurred in the treatment of diarrhea when it was discovered that glucose could enhance intestinal sodium and water absorption. Adding glucose to salt water (oral rehydration solution, ORS) more efficiently replaced intestinal water and salt losses. AIM: Provide a novel hypothesis to explain why mainstream use of ORS has been strongly recommended, but weakly adopted. METHODS: Traditional (absorptive) and novel (secretory) physiological functions of glucose in an ORS were reviewed. RESULTS: Small amounts of glucose can stimulate both intestinal absorption and secretion. Glucose can exacerbate a net secretory state and may aggravate pathogen-induced diarrhea, particularly for pathogens that affect glucose transport. CONCLUSION: A hypothesis is made to explain why glucose-based ORS does not appreciably reduce diarrheal stool volume and why modern food science initiatives should focus on ORS formulations that replace water and electrolytes while also reducing stool volume and duration of diarrhea.


Assuntos
Diarreia , Soluções para Reidratação , Diarreia/terapia , Glucose , Humanos , Sódio
4.
Am J Med Genet B Neuropsychiatr Genet ; 171B(2): 266-75, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26590516

RESUMO

Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P < 0.05, 30 days) and Total Scores (Ƶ = 2.3, P < 0.02, 30 days), and participant ratings of the DHQ Severity (Ƶ = 1.8, P < 0.06, 5 days) and Total Scores (Ƶ = 1.9, P < 0.05, 15 days). These findings support sustained neuromodulatory effects and efficacy of tDCS to reduce food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS.


Assuntos
Comportamento , Fissura , Hiperfagia/complicações , Hiperfagia/terapia , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/terapia , Estimulação Transcraniana por Corrente Contínua , Adulto , Peso Corporal , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Inquéritos e Questionários
5.
Cancer Res Commun ; 4(3): 660-670, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38391189

RESUMO

PURPOSE: Chronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN. EXPERIMENTAL DESIGN: We randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. RESULTS: The Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. CONCLUSIONS: With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions. SIGNIFICANCE: Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.


Assuntos
Dieta Mediterrânea , Transtornos Mieloproliferativos , Neoplasias , Humanos , Estados Unidos , Projetos Piloto , Estudos de Viabilidade , Transtornos Mieloproliferativos/terapia , Inflamação , Nutrientes
6.
Waste Manag Res ; 31(7): 733-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23592758

RESUMO

Healthcare waste (HCW) management and segregation are essential to ensure safety, environmental protection and cost control. Poor HCW management increase risks and costs for healthcare institutions. On-going surveillance and training are important to maintain good HCW practices. Our objectives were to evaluate and improve HCW practices at Hospital Bloom, San Salvador, El Salvador. We studied HCW disposal practices by observing waste containers, re-segregating waste placed in biohazardous waste bags, and administering a seven-itemsknowledge survey before and after training in waste management at Hospital Bloom. The training was based on national and international standards. We followed total biohazardous waste production before and after the training. The hospital staff was knowledgeable about waste segregation practices, but had poor compliance with national policies. Re-segregating waste in biohazardous waste bags showed that 61% of this waste was common waste, suggesting that the staff was possibly unaware of the cost of mis-segregating healthcare waste. After staff training in HCW management, the correct responses increased by 44% and biohazardous waste disposal at the hospital reduced by 48%. Better segregation of biohazardous waste and important savings can be obtained by HCW management education of hospital staff. Hospitals can benefit from maximising the use of available resources by sustaining best practices of HCW, especially those in hospitals in lower-middle-income countries.


Assuntos
Controle de Custos , Hospitais Públicos/organização & administração , Renda , Gerenciamento de Resíduos , Países em Desenvolvimento , El Salvador , Hospitais Públicos/economia , Gerenciamento de Resíduos/economia , Gerenciamento de Resíduos/normas
7.
mBio ; : e0230823, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37877698

RESUMO

Myeloproliferative neoplasms (MPNs) are a class of rare hematological malignancies that result in the overproduction of myeloid lineage cells. These malignancies result in increased cytokine production and inflammation, which correlate with worsened symptom burden and prognosis. Other than bone marrow transplantation, there is no cure for myeloproliferative neoplasms. As such, treatments focus on reducing thrombotic risk, inflammation, and symptom burden. Because current pharmacological treatments carry significant side effects, there is a need to explore low-risk therapies that may modulate inflammation and alleviate symptom burden. One potential way to achieve this is adherence to a Mediterranean (MED) diet, which is rich in anti-inflammatory foods, reduces inflammatory biomarkers, and beneficially alters the gut microbiome. We performed a 15-week clinical trial of 28 individuals with MPN who were randomized to dietary counseling based on either a Mediterranean diet or standard U.S. Guidelines for Americans. Our primary objective was to determine whether MPN patients could adopt a Mediterranean eating pattern when supported with dietician counseling. As exploratory endpoints, we investigated the impact of diet and inflammation on the gut microbiome. Using shotgun metagenomic sequencing, we found that microbiome diversity and composition were stable throughout the study duration in both cohorts. Furthermore, we discovered significant differences in the microbiomes between MPN subtypes, such as increased beta-dispersion in subjects with myelofibrosis. Lastly, we found several significant correlations between the abundance of multiple bacterial taxa and cytokine levels. Together, this study provides insight into the interaction between diet, inflammation, and the gut microbiome. IMPORTANCE The gut microbiome serves as an interface between the host and the diet. Diet and the gut microbiome both play important roles in managing inflammation, which is a key aspect of myeloproliferative neoplasm (MPN). Studies have shown that a Mediterranean (MED) diet can reduce inflammation. Therefore, we longitudinally characterized the gut microbiomes of MPN patients in response to Mediterranean or standard 2020 US Guidelines for Americans dietary counseling to determine whether there were microbiome-associated changes in inflammation. We did not find significant changes in the gut microbiome associated with diet, but we did find several associations with inflammation. This research paves the way for future studies by identifying potential mechanistic targets implicated in inflammation within the MPN gut microbiome.

8.
medRxiv ; 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37214789

RESUMO

Purpose: Chronic inflammation is integral to Myeloproliferative Neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among MPN patients. Experimental Design: We randomly assigned participants to either a Mediterranean diet or standard US Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four time points during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. Results: The Mediterranean diet was as easy to follow for MPN patients as the standard USDA diet. Over 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any time point. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. Conclusions: With dietician counseling and written education MPN patients can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially even be incorporated into the management of other chronic clonal hematologic conditions.

9.
Microbiol Spectr ; 10(3): e0003222, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35475626

RESUMO

The capacity of the human microbiome to modulate inflammation in the context of cancer is becoming increasingly clear. Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies in which inflammation plays a key role in disease initiation, progression, and symptomatology. To better understand the composition of the gut microbiome in patients with MPN, triplicate fecal samples were collected from 25 MPN patients and 25 non-MPN controls. Although most of the variance between the microbial community compositions could be attributed to the individual (permutational analysis of variance [PERMANOVA], R2 = 0.92, P = 0.001), 1.7% of the variance could be attributed to disease status (MPN versus non-MPN). When a more detailed analysis was performed, significantly fewer reads mapping to a species of Phascolarctobacterium, a microbe previously associated with reduced inflammation, were found in MPNs. Further, our data revealed an association between Parabacteroides and tumor necrosis factor alpha (TNF-α), an inflammatory cytokine elevated in MPNs. Taken together, our results indicate a significant difference in the microbiome of MPN patients compared to non-MPN controls, and we identify specific species which may have a role in the chronic inflammation central to this disease. IMPORTANCE MPNs are chronic blood cancers in which inflammation plays a key role in disease initiation, progression, and symptomatology. The gut microbiome modulates normal blood development and inflammation and may also impact the development and manifestation of blood cancers. Therefore, the microbiome may be an important modulator of inflammation in MPN and could potentially be leveraged therapeutically in this disease. However, the relationship between the gut microbiome and MPNs has not been defined. Therefore, we performed an evaluation of the MPN microbiome, comparing the microbiomes of MPN patients with healthy donors and between MPN patients with various states of disease.


Assuntos
Microbioma Gastrointestinal , Transtornos Mieloproliferativos , Neoplasias , Doença Crônica , Fezes , Humanos , Inflamação , Transtornos Mieloproliferativos/patologia
10.
J Affect Disord ; 302: 110-122, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35032507

RESUMO

INTRODUCTION: Health-care Workers (HCW) are facing a critical situation caused by Coronavirus Disease 2019 (COVID-19) which could impact on their mental health status. In addition, HCW women have been identified as a group at high-risk of developing psychological distress, although no previous longitudinal studies have explored this issue in a sample of HCW. AIMS: The main aim of the study was to observe the temporal pattern of the stress reactions among HCW as well as to explore its potential predictors of poor outcome. Moreover, we analyzed possible gender differences in stress reaction responses. METHODS: One thousand for hundred and thirty-two HCW responded an online survey including sociodemographic, clinical, and psychometric tests in May 2020 while 251 HCW answered in November 2020. Bivariate and multivariate analyses as well as repeated measures analyses were used to achieve the aims of the study. RESULTS: The proportion of HCW who fulfilled Acute Stress Disorder criteria did not change over the follow-up period, although we observed a significant improvement in stress reactions responses among HCW. Proximal factors were the most salient predictors of traumatic reactions. Repeated analyses revealed significant gender differences in acute stress reactions. In addition, women showed significantly greater improvement than men in re-experiencing the traumatic event and hyperarousal dimensions. CONCLUSIONS: Monitoring of working conditions as well as emotional reactions in HCW facing major disasters should be carried out to prevent the development of peritraumatic stress reactions. In addition, HCW women are characterized by a different pattern of progression in stress responses.


Assuntos
COVID-19 , Feminino , Pessoal de Saúde/psicologia , Humanos , Estudos Longitudinais , Masculino , Pandemias , Estudos Prospectivos , SARS-CoV-2
11.
Diagnostics (Basel) ; 12(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36359595

RESUMO

The present systematic review and meta-analysis about the accuracy of diagnostic tests aim to describe the findings of literature over the last thirty years for the diagnosis of Chagas disease (CD). This work aimed to determine the accuracy of diagnostic techniques for CD in the disease's acute and chronic phases. The PubMed database was searched for studies published between 1990 and 2021 on CD diagnostics. Fifty-six published studies that met the criteria were analyzed and included in the meta-analysis, evaluating diagnostic accuracy through sensitivity and specificity. For Enzyme-Linked Immunosorbent Assay (ELISA), Fluorescent Antibody Technique (IFAT), Hemagglutination Test (HmT), Polymerase Chain Reaction (PCR), and Real-Time Polymerase Chain Reaction (qPCR) diagnosis methods, the sensitivity had a median of 99.0%, 78.0%, 75.0%, 76.0%, and 94.0%, respectively; while specificity presented a median of 99.0%, 99.0%, 99.0%, 98.0%, and 98.0%, respectively. This meta-analysis showed that ELISA and qPCR techniques had a higher performance compared to other methods of diagnosing CD in the chronic and acute phases, respectively. It was concluded utilizing the Area Under the Curve restricted to the false positive rates (AUCFPR), that the ELISA diagnostic test presents the highest performance in diagnosing acute and chronic CD, compared to serological and molecular tests. Future studies focusing on new CD diagnostics approaches should be targeted.

12.
J Virol ; 84(2): 810-21, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19906935

RESUMO

While the molecular basis of fusion (F) protein refolding during membrane fusion has been studied extensively in vitro, little is known about the biological significance of membrane fusion activity in parainfluenza virus replication and pathogenesis in vivo. Two recombinant Sendai viruses, F-L179V and F-K180Q, were generated that contain F protein mutations in the heptad repeat A region of the ectodomain, a region of the protein known to regulate F protein activation. In vitro, the F-L179V virus caused increased syncytium formation (cell-cell membrane fusion) yet had a rate of replication and levels of F protein expression and cleavage similar to wild-type virus. The F-K180Q virus had a reduced replication rate along with reduced levels of F protein expression, cleavage, and fusogenicity. In DBA/2 mice, the hyperfusogenic F-L179V virus induced greater morbidity and mortality than wild-type virus, while the attenuated F-K180Q virus was much less pathogenic. During the first week of infection, virus replication and inflammation in the lungs were similar for wild-type and F-L179V viruses. After approximately 1 week of infection, the clearance of F-L179V virus was delayed, and more extensive interstitial inflammation and necrosis were observed in the lungs, affecting entire lobes of the lungs and having significantly greater numbers of syncytial cell masses in alveolar spaces on day 10. On the other hand, the slower-growing F-K180Q virus caused much less extensive inflammation than wild-type virus, presumably due to its reduced replication rate, and did not cause observable syncytium formation in the lungs. Overall, the results show that residues in the heptad repeat A region of the F protein modulate the virulence of Sendai virus in mice by influencing both the spread and clearance of the virus and the extent and severity of inflammation. An understanding of how the F protein contributes to infection and inflammation in vivo may assist in the development of antiviral therapies against respiratory paramyxoviruses.


Assuntos
Regulação Viral da Expressão Gênica , Vírus Sendai/patogenicidade , Proteínas Virais de Fusão/química , Animais , Linhagem Celular , Chlorocebus aethiops , Feminino , Pulmão/patologia , Pulmão/virologia , Fusão de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos DBA , Mutação Puntual , Infecções por Respirovirus/mortalidade , Infecções por Respirovirus/fisiopatologia , Infecções por Respirovirus/virologia , Vírus Sendai/genética , Vírus Sendai/metabolismo , Células Vero , Proteínas Virais de Fusão/metabolismo , Virulência
13.
Asian Pac J Cancer Prev ; 22(1): 301-304, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507712

RESUMO

High-dose chemotherapy frequently causes injury to the gastrointestinal mucosa, resulting in diarrhea. The purpose of the current study was to assess the tolerability and efficacy of enterade® in reducing ≥ grade 2 diarrhea (G2D) in association with high-dose melphalan followed by autologous stem cell transplantation (ASCT). We conducted a prospective, double blinded, multi-center trial in which 114 subjects were randomized to receive enterade® or placebo twice daily during the transplant hospitalization. Gastrointestinal toxicities (nausea, vomiting, oral mucositis and dysphagia) resulted in poor study compliance in both arms. Among subjects who were able to complete planned therapy (13%), the incidence of G2D was lower for those receiving enterade® as compared to placebo (16% vs 86%, p <0.03). Twice daily oral administration of enterade® and placebo following high-dose chemotherapy and ASCT was not feasible due to significant gastrointestinal toxicities.  Future explorations of enterade® should be conducted in populations capable of reasonable oral intake.
.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diarreia/dietoterapia , Dieta , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adulto , Idoso , Terapia Combinada , Diarreia/etiologia , Diarreia/patologia , Método Duplo-Cego , Feminino , Seguimentos , Abastecimento de Alimentos , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Prognóstico , Estudos Prospectivos , Condicionamento Pré-Transplante , Transplante Autólogo
14.
Psicothema ; 33(2): 188-197, 2021 05.
Artigo em Espanhol | MEDLINE | ID: mdl-33879290

RESUMO

Evidence-Based Psychological Treatments for Adults: A Selective Review. BACKGROUND: Psychological treatments have shown their efficacy, effectiveness, and efficiency in dealing with mental disorders. However, considering the scientific knowledge generated in recent years, in the Spanish context, there are no updating studies about empirically supported psychological treatments. The main goal was to carry out a selective review of the main empirically supported psychological treatments for mental disorders in adults. METHOD: Levels of evidence and degrees of recommendation were collected based on the criteria proposed by the Spanish National Health System (Clinical Practice Guidelines) for different psychological disorders. RESULTS: The results indicate that psychological treatments have empirical support for the approach to a wide range of psychological disorders. These levels of empirical evidence gathered range from low to high depending on the psychological disorder analysed. The review indicates the existence of certain fields of intervention that need further investigation. CONCLUSIONS: Based on this selective review, psychology professionals will be able to have rigorous, up-to-date information that allows them to make informed decisions when implementing empirically based psychotherapeutic procedures based on the characteristics of the people who require help.


Assuntos
Transtornos Mentais , Adulto , Humanos , Transtornos Mentais/terapia
15.
Blood Adv ; 4(2): 312-321, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31978215

RESUMO

Thrombosis is a major cause of mortality in patients with myeloproliferative neoplasms (MPNs), though there is currently little to offer patients with MPN beyond aspirin and cytoreductive therapies such as hydroxyurea for primary prevention. Thrombogenesis in MPN involves multiple cellular mechanisms, including platelet activation and neutrophil-extracellular trap formation; therefore, an antithrombotic agent that targets one or more of these processes would be of therapeutic benefit in MPN. Here, we treated the JAK2V617F knockin mouse model of polycythemia vera with N-acetylcysteine (NAC), a sulfhydryl-containing compound with broad effects on glutathione replenishment, free radical scavenging, and reducing disulfide bonds, to investigate its antithrombotic effects in the context of MPN. Strikingly, NAC treatment extended the lifespan of JAK2V617F mice without impacting blood counts or splenomegaly. Using an acute pulmonary thrombosis model in vivo, we found that NAC reduced thrombus formation to a similar extent as the irreversible platelet inhibitor aspirin. In vitro analysis of platelet activation revealed that NAC reduced thrombin-induced platelet-leukocyte aggregate formation in JAK2V617F mice. Furthermore, NAC reduced neutrophil extracellular trap formation in primary human neutrophils from patients with MPN as well as healthy controls. These results provide evidence that N-acetylcysteine inhibits thrombosis in JAK2V617F mice and provide a pre-clinical rationale for investigating NAC as a therapeutic to reduce thrombotic risk in MPN.


Assuntos
Acetilcisteína/uso terapêutico , Transtornos Mieloproliferativos/tratamento farmacológico , Trombose/tratamento farmacológico , Acetilcisteína/farmacologia , Animais , Humanos , Masculino , Camundongos
16.
Curr Hematol Malig Rep ; 14(3): 145-153, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31119475

RESUMO

PURPOSE OF REVIEW: Chronic inflammation is a characteristic feature of myeloproliferative neoplasm (MPN) and impacts many aspects of the disease including initiation, progression, and symptomatology. RECENT FINDINGS: The chronic inflammatory state of MPN results from disruption of immune signaling pathways leading to overproduction of inflammatory cytokines by both the neoplastic clones and bystander immune cells. This chronic inflammation may allow for the neoplastic clone to gain a selective advantage. The symptomatic burden felt by MPN patients may be a result of the chronic inflammation associated with MPN, as several cytokines have been linked with different symptoms. Pharmacologic as well as nonpharmacologic treatments of the inflammatory component of this disease may lead to decreased symptomatic burden, prevention of disease progression, and improvement in overall disease trajectory. Inflammation plays a key role in the pathogenesis of MPN and represents an important therapeutic target.


Assuntos
Inflamação/complicações , Transtornos Mieloproliferativos/etiologia , Doença Crônica , Progressão da Doença , Humanos
17.
Trends Microbiol ; 14(6): 243-6, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16678421

RESUMO

To deliver their genetic material into host cells, enveloped viruses have surface glycoproteins that actively cause the fusion of the viral and cellular membranes. Recently determined X-ray crystal structures of the paramyxovirus fusion (F) protein in its pre-fusion and post-fusion conformations reveal the dramatic structural transformation that this protein undergoes while causing membrane fusion. Conformational changes in key regions of the F protein suggest the mechanism by which the F protein is activated and refolds.


Assuntos
Fusão de Membrana/fisiologia , Paramyxoviridae/fisiologia , Proteínas Virais de Fusão/química , Conformação Proteica , Estrutura Terciária de Proteína/fisiologia , Proteínas Virais de Fusão/metabolismo
18.
J Pediatr Endocrinol Metab ; 29(1): 103-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26353172

RESUMO

INTRODUCTION: Prepubertal gynecomastia is a rare condition characterized by the growth of breast tissue in males as a consequence of early exposure to sexual hormones. When this condition is present, pathological sources of testosterone/estrogen production, such as adrenal or gonadal tumors must be searched for. A few reports have described an association between gynecomastia and substances that produce stimulation of the estrogen receptor, such as lavender and tea tree oil. METHODS: Here we describe the cases of three boys who presented with prepubertal gynecomastia and were chronically exposed to lavender. Two of these boys were exposed to a cologne, named agua de violetas, used by Hispanic communities in the US, and in their countries of origin. RESULTS: We studied a sample of the cologne used by one of the patients. Analysis of the chemical composition of the agua de violetas cologne was performed using high-performance liquid chromatography as well as off-line mass spectrometric detection. All these, combined with the physical appearance and the smell, determined that the cologne had lavender as an ingredient. CONCLUSION: Exposure to estrogenic substances, such as lavender, should be explored in children presenting with prepubertal gynecomastia/thelarche.


Assuntos
Ginecomastia/induzido quimicamente , Ginecomastia/diagnóstico , Lavandula/química , Óleos Voláteis/efeitos adversos , Óleos de Plantas/efeitos adversos , Puberdade/efeitos dos fármacos , Criança , Humanos , Masculino
20.
Vaccine ; 26(27-28): 3480-8, 2008 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-18499307

RESUMO

The human parainfluenza viruses (hPIVs) and respiratory syncytial virus (RSV) are the leading causes of serious respiratory illness in the human pediatric population. Despite decades of research, there are currently no licensed vaccines for either the hPIV or RSV pathogens. Here we describe the testing of hPIV-3 and RSV candidate vaccines using Sendai virus (SeV, murine PIV-1) as a vector. SeV was selected as the vaccine backbone, because it has been shown to elicit robust and durable immune activities in animal studies, and has already advanced to human safety trials as a xenogenic vaccine for hPIV-1. Two new SeV-based hPIV-3 vaccine candidates were first generated by inserting either the fusion (F) gene or hemagglutinin-neuraminidase (HN) gene from hPIV-3 into SeV. The resultant rSeV-hPIV3-F and rSeV-hPIV3-HN vaccines expressed their inserted hPIV-3 genes upon infection. The inoculation of either vaccine into cotton rats elicited binding and neutralizing antibody activities, as well as interferon-gamma-producing T cells. Vaccination of cotton rats resulted in protection against subsequent challenges with either homologous or heterologous hPIV-3. Furthermore, vaccination of cotton rats with a mixture of rSeV-hPIV3-HN and a previously described recombinant SeV expressing the F protein of RSV resulted in protection against three different challenge viruses: hPIV-3, hPIV-1 and RSV. Results encourage the continued development of the candidate recombinant SeV vaccines to combat serious respiratory infections of children.


Assuntos
Proteína HN/imunologia , Vacinas contra Parainfluenza/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Infecções por Respirovirus/prevenção & controle , Vírus Sendai/genética , Proteínas Virais de Fusão/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/sangue , Feminino , Vetores Genéticos , Proteína HN/genética , Pulmão/virologia , Dados de Sequência Molecular , Vacinas contra Parainfluenza/genética , Ratos , Vacinas contra Vírus Sincicial Respiratório/genética , Sigmodontinae , Linfócitos T/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas Virais de Fusão/genética
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