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1.
Am J Trop Med Hyg ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31595865

RESUMO

Buruli ulcer (BU) is a neglected tropical disease caused by infection with Mycobacterium ulcerans. Unclear transmission, no available vaccine, and suboptimal treatment regimens hamper the control of this disease. Carefully designed preclinical research is needed to address these shortcomings. In vivo imaging (IVIS®) of infection is an emerging tool that permits monitoring of disease progression and reduces the need to using large numbers of mice at different time-points during the experiment, as individual mice can be imaged at multiple time-points. We aimed to further describe the use of in vivo imaging (IVIS) in BU. We studied the detection of M. ulcerans in experimentally infected BALB/c mouse tails and the subsequent histopathology and immune response in this pilot study. IVIS-monitoring was performed weekly in ten infected BALB/c mice to measure light emitted as a proxy for bacterial load. Nine of 10 (90%) BALB/c mice infected subcutaneously with 3.3 × 105 M. ulcerans JKD8049 (containing pMV306 hsp16+luxG13) exhibited light emission from the site of infection, indicating M. ulcerans growth in vivo, whereas only five of 10 (50%) animals developed clinical signs of the disease. Specific antibody titers were detected within 2 weeks of the infection. IFN-γ and IL-10 were elevated in animals with pathology. Histopathology revealed clusters of acid-fast bacilli in the subcutaneous tissue, with macrophage infiltration and granuloma formation resembling human BU. Our study successfully showed the utility of M. ulcerans IVIS monitoring and lays a foundation for further research.

2.
Clin Infect Dis ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31642899

RESUMO

BACKGROUND: The (H1N1)pdm09 live attenuated influenza vaccine (LAIV) strain was changed for the 2017-2018 influenza season to improve viral fitness, following poor protection against (H1N1)pdm09 viruses in 2015-2016. We conducted LAIV virus shedding studies to assess the effect of this change. METHODS: Children aged 2-18 years were recruited to receive LAIV in the 2016-2017 (n = 641) and 2017-2018 (n = 362) influenza seasons. Viruses from nasal swabs taken 1, 3, and 6 days postvaccination were quantified by reverse-transcription polymerase chain reaction and area under the curve titers were determined. Presence and quantity of shedding were compared between strains and seasons with adjustment for age and prior LAIV (n = 436), inactivated seasonal vaccine (n = 100), or (H1N1)pdm09 vaccine (n = 166) receipt. RESULTS: (H1N1)pdm09 detection (positivity) in 2016-2017 and 2017-2018 (11.2% and 3.9%, respectively) was lower than that of H3N2 (19.7% and 18.7%, respectively) and B/Victoria (28.9% and 33.9%, respectively). (H1N1)pdm09 positivity was higher in 2016-2017 than 2017-2018 (P = .005), but within shedding-positive participants, the (H1N1)pdm09 titer increased in 2017-2018 (P = .02). H3N2 and influenza B titers were similar between seasons. Positivity declined with age, and prior vaccination reduced the likelihood of shedding influenza B but not (H1N1)pdm09. CONCLUSIONS: The (H1N1)pdm09 titer increased in 2017-2018, indicating more efficient virus replication in shedding-positive children than the 2016-2017 strain, although overall positivity was reduced. Age and vaccination history require consideration when correlating virus shedding and protection. CLINICAL TRIALS REGISTRATION: NCT02143882, NCT02866942, and NCT03104790.

3.
Mil Med ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498403

RESUMO

INTRODUCTION: Service members are exposed to ambient airborne pollutants that have been linked to adverse health effects; however, capabilities to identify and characterize exposures across multi-domain operations are currently lacking. Occupational and environmental exposure monitoring is problematic because there is not a single simple solution, and current technological limitations suggest that simultaneous deployment of multiple devices may be the most effective near-term strategy. MATERIALS AND METHODS: A broad industry scan of wearable, handheld, or portable occupational and environmental exposure monitoring devices was conducted, and subject matter experts were interviewed about the state of the field. RESULTS: This survey identified limitations including the inability to detect multiple analytes or analyte classes, size and weight, and detection limits, but multiple implementation strategies could be employed to meet a variety of combat needs. Device types could be layered, or specific device types could be deployed in acute toxic exposure environments such as dense urban population centers or subterranean spaces. CONCLUSIONS: Evolving technologies and data management strategies may advance personal exposure monitoring in the future. These new devices and methods will likely supplant current technologies, while still using the programmatic and data framework established with early implementation of current commercial off the shelf devices.

4.
Plant Cell Physiol ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393575

RESUMO

In plants, the stem cells that form the shoot system reside within the shoot apical meristem (SAM), which is regulated by feedback signaling between the WUSCHEL (WUS) homeobox protein and CLAVATA (CLV) peptides and receptors. WUS-CLV feedback signaling can be modulated by various endogenous or exogenous factors such as chromatin state, hormone signaling, reactive oxygen species (ROS) signaling and nutrition, leading to a dynamic control of SAM size corresponding to meristem activity. Despite these insights, however, the knowledge of genes that control SAM size is still limited, and in particular the regulation by ROS signaling is only beginning to be comprehended. Here, we report a new gene that functions in SAM size maintenance, OKINA KUKI (OKI1), which is expressed in the SAM and encodes a mitochondrial aspartyl tRNA synthetase (AspRS). oki1 mutants display enlarged SAMs with abnormal expression of WUS and CLV3, and overaccumulation of ROS in the meristem. Our findings support the importance of normal AspRS function in the maintenance of the WUS-CLV3 feedback loop and SAM size.

5.
J Surg Res ; 245: 115-118, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31415932

RESUMO

BACKGROUND: The autoimmune process and increased TSH associated with chronic lymphocytic thyroiditis (CLT) are factors that may promote development of thyroid cancer. When surgically removed, the cellular changes of CLT are commonly seen surrounding thyroid cancers. This study investigates the malignancy rate in CLT patients when compared with non-CLT patients after thyroidectomy. METHODS: A retrospective review of prospectively collected data for 1268 patients with index thyroid nodules who underwent thyroidectomy at a single institution was performed. Patients were excluded if they had previous thyroid surgery, known thyroid cancer, Graves' disease, family history of thyroid cancer, and history of radiation exposure. Patients were subdivided into CLT and non-CLT groups by final pathology. Final pathology was reviewed and grouped into cancer in the index thyroid nodule and incidental thyroid cancers. Chi-squared analyses were performed using SAS. RESULTS: Of 359 patients that met study criteria, 52 had CLT. Overall, the malignancy rate was 37% in both CLT patients (19/52) and non-CLT patients (114/307) (P = 0.86). However, incidental thyroid cancer was found in 15% (8/52) of CLT patients and 10% (31/307) of non-CLT patients (relative risk = 1.52) who had no index nodule cancer. The breakdown of incidental cancer subtype in CLT patients was classic variant papillary thyroid carcinoma (PTC), n = 3; follicular variant PTC, n = 5. CONCLUSIONS: Patients with CLT have a 1.5-fold increased risk of incidental PTC. CLT should be considered a risk factor for incidental thyroid cancer, and patients with this thyroid condition should be counseled and monitored periodically for underlying thyroid malignancy.

6.
Ann Am Thorac Soc ; 16(8): e1-e16, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31368802

RESUMO

Since 2001, more than 2.7 million U.S. military personnel have been deployed in support of operations in Southwest Asia and Afghanistan. Land-based personnel experienced elevated exposures to particulate matter and other inhalational exposures from multiple sources, including desert dust, burn pit combustion, and other industrial, mobile, or military sources. A workshop conducted at the 2018 American Thoracic Society International Conference had the goals of: 1) identifying key studies assessing postdeployment respiratory health, 2) describing emerging research, and 3) highlighting knowledge gaps. The workshop reviewed epidemiologic studies that demonstrated more frequent encounters for respiratory symptoms postdeployment compared with nondeployers and for airway disease, predominantly asthma, as well as case series describing postdeployment dyspnea, asthma, and a range of other respiratory tract findings. On the basis of particulate matter effects in other populations, it also is possible that deployers experienced reductions in pulmonary function as a result of such exposure. The workshop also gave particular attention to constrictive bronchiolitis, which has been reported in lung biopsies of selected deployers. Workshop participants had heterogeneous views regarding the definition and frequency of constrictive bronchiolitis and other small airway pathologic findings in deployed populations. The workshop concluded that the relationship of airway disease, including constrictive bronchiolitis, to exposures experienced during deployment remains to be better defined. Future clinical and epidemiologic research efforts should address better characterization of deployment exposures; carry out longitudinal assessment of potentially related adverse health conditions, including lung function and other physiologic changes; and use rigorous histologic, exposure, and clinical characterization of patients with respiratory tract abnormalities.

7.
Int J Pharm Compd ; 23(4): 340-350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31315086

RESUMO

The objective of this study was to develop a validated stability-indicating high-performance liquid chromatographic method that quantifies progesterone in compounded glycerinated gelatin troches. The mobile phase was composed of methanol and water (75:25 v/v), while the stationary phase was a Waters Nova-Pak C18 column (3.9 mm Å~ 15 cm Å~ 4.0 µm) with the column's temperature set to 40°C. The injection volume was 20 µL, while the gradient flow rate was maintained at 0.75 mL/min for a run time of 15 minutes. The detection wavelength for progesterone was set to 245 nm. In the forced degradation study, there was significant hydrolytic, oxidative, ultraviolet, and thermal degradation but insignificant photodegradation. However, no degradants co-eluted with progesterone. All method validation parameters met the respective acceptance criteria established by the International Conference on Harmonisation guidelines. This developed and validated method is suitable for both routine potency/strength testing as well as stability testing of progesterone in compounded glycerinated gelatin troche dosage forms. The method was utilized to successfully quantify progesterone in multiple compounded preparations from two different compounding pharmacies.


Assuntos
Gelatina , Progesterona , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos
8.
Nat Genet ; 51(6): 1052-1059, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152161

RESUMO

Maize is one of the most important crops globally, and it shows remarkable genetic diversity. Knowledge of this diversity could help in crop improvement; however, gold-standard genomes have been elucidated only for modern temperate varieties. Here, we present a high-quality reference genome (contig N50 of 15.78 megabases) of the maize small-kernel inbred line, which is derived from a tropical landrace. Using haplotype maps derived from B73, Mo17 and SK, we identified 80,614 polymorphic structural variants across 521 diverse lines. Approximately 22% of these variants could not be detected by traditional single-nucleotide-polymorphism-based approaches, and some of them could affect gene expression and trait performance. To illustrate the utility of the diverse SK line, we used it to perform map-based cloning of a major effect quantitative trait locus controlling kernel weight-a key trait selected during maize improvement. The underlying candidate gene ZmBARELY ANY MERISTEM1d provides a target for increasing crop yields.


Assuntos
Estudos de Associação Genética , Genoma de Planta , Genômica , Fenótipo , Zea mays/genética , Biologia Computacional/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Endogamia , Anotação de Sequência Molecular , Melhoramento Vegetal , Plantas Geneticamente Modificadas , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável
9.
Zoonoses Public Health ; 66(5): 504-511, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152500

RESUMO

Mass bat exposures (MBEs) occur when multiple people are exposed to a bat or a bat colony, often over an extended period. In August 2017, a public health investigation was started in response to an MBE that occurred during May-August 2017 at a national park research station in Wyoming. We identified 176 people who had slept primarily in two lodges (Lodges A and B) at the research station, and successfully contacted 165 (93.8%) of these individuals. Risk assessments (RAs) were administered to all 165 individuals to determine degree and type of exposures to bats (e.g., biting or scratching). Exposure status for research station guests was classified as "non-exposed," "low risk" or "high risk," and counselling was provided to guide post-exposure prophylaxis (PEP) recommendations. Prior to public health notification and intervention, 19 persons made the decision to pursue PEP. The healthcare-seeking behaviours of this group were taken to represent outcomes in the absence of public health intervention. (These persons received a RA, and their risk classification was retrospectively assigned.) Approximately 1-2 weeks after conducting the RAs, we conducted a follow-up survey to determine whether recommendations regarding PEP were ultimately followed. The proportion of individuals that unnecessarily pursued PEP was higher among the 19 individuals that sought health care prior to receiving the RA (p < 0.00001). Among those receiving the RA first, all persons classified as high risk followed public health guidance to seek PEP treatment. Despite this, upon re-interview, only 21/79 (26.6%) of guests could accurately recall their risk classification, with most people (55.7%) overestimating their risk. Study findings demonstrate that early public health interventions such as RAs can reduce unnecessary use of PEP and that messaging used during rabies counselling should be clear.


Assuntos
Quirópteros , Doenças Transmissíveis/transmissão , Zoonoses/epidemiologia , Animais , Controle de Doenças Transmissíveis , Habitação , Humanos , Parques Recreativos , Profilaxia Pós-Exposição , Saúde Pública , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Wyoming/epidemiologia
10.
J Matern Fetal Neonatal Med ; : 1-3, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31230488

RESUMO

Purpose: To determine the negative and positive predictive values of hemoglobin A1c (HgbA1c) levels in predicting abnormal 1-hour glucose challenge test (GCT) results in pregnancy. Methods: This retrospective cohort study consisted of pregnant patients from a private practice obstetrics clinic. The primary exposure was early HgbA1c measurement, and the primary outcome was third trimester 1-hour GCT results above or below 140 mg/dL. We calculated the predictive value of early HgbA1c to identify a 1-hour GCT of ≤140 mg/dL or >140 mg/dL. Results: Of the 1404 one-hour GCT results, 635 were associated with HgbA1c being measured in a patient on the same day or before the 1-hour GCT. The median interval between the HgbA1c test and the 1-hour GCT was 95 days (IQR 56-122 days). Among women with a hgbA1c less than or equal to 4.9, 5.0 and 5.1, respectively, the probability of their 1 hour GCT being 140 mg/dl or less was 91.3%, 91.0% and 90.1%, respectively ( Table 1 ). Among our study population, 14.5%, 22.8% and 35.0% had an Hgb A1c less than or equal to 4.9, 5.0 and 5.1 respectively. Among women with HgbA1c greater than 6.1, the probability of their 1-hour GCT being greater than 140 mg/dL was 100%. Only 0.3% of our population had HgbA1c greater than 6.1. There was no other cut point for HgbA1c, where the positive predictive value for predicting an abnormal 1-hour GCT was equal to or greater than 90%. Conclusions: The greatest value of an early HgbA1C test appears to be that very low values (5.1 or less) can predict a normal 1 h GCT with high probability (at least 90%). However, it has limited ability to predict abnormal 1 h GCT. Overall, an early HgbA1C cannot replace the 1 h GCT based on the current body of evidence.

11.
Nat Chem Biol ; 15(7): 669-671, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209348

RESUMO

Fatty acid synthases are dynamic ensembles of enzymes that can biosynthesize long hydrocarbon chains efficiently. Here we visualize the interaction between the Escherichia coli acyl carrier protein (AcpP) and ß-ketoacyl-ACP-synthase I (FabB) using X-ray crystallography, NMR, and molecular dynamics simulations. We leveraged this structural information to alter lipid profiles in vivo and provide a molecular basis for how protein-protein interactions can regulate the fatty acid profile in E. coli.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Proteína de Transporte de Acila/metabolismo , Proteínas de Escherichia coli/metabolismo , Ácido Graxo Sintase Tipo II/metabolismo , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/química , Proteína de Transporte de Acila/química , Cristalografia por Raios X , Escherichia coli/química , Escherichia coli/enzimologia , Proteínas de Escherichia coli/química , Ácido Graxo Sintase Tipo II/química , Modelos Moleculares , Ligação Proteica
12.
Adm Policy Ment Health ; 46(5): 609-619, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31152274

RESUMO

Over the past several years, youth treatment research has moved toward understanding the dissemination and implementation of evidence-based practices (EBPs). As a result, studies have focused on identifying predictors that aid in successful adoption and sustainment of EBPs. Theories of behavior change posit that therapist knowledge and attitudes play a fundamental role in EBP adoption; however, studies have produced mixed findings, which may be an artifact of broad definitions of both EBP knowledge and EBP itself. The current study was an examination of 46 youth community therapists and the extent to which varying types of knowledge and attitudes as well as youth characteristics predicted specific practices derived from the evidence-base. Results suggested that specific EBP knowledge predicted specific practices, highlighting the need for more specificity when examining predictors of EBP use. Therapists' attitudes, demographic characteristics, and youth characteristics were also significant predictors of EBP use. Future research should consider examining discrete and specific practices to better understand and predict therapists' future behavior.

13.
Annu Rev Plant Biol ; 70: 269-291, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035828

RESUMO

A fascinating feature of plant growth and development is that plants initiate organs continually throughout their lifespan. The ability to do this relies on specialized groups of pluripotent stem cells termed meristems, which allow for the elaboration of the shoot, root, and vascular systems. We now have a deep understanding of the genetic networks that control meristem initiation and stem cell maintenance, including the roles of receptors and their ligands, transcription factors, and integrated hormonal and chromatin control. This review describes these networks and discusses how this knowledge is being applied to improve crop productivity by increasing fruit size and seed number.

14.
Nat Genet ; 51(5): 786-792, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30988512

RESUMO

Precise control of plant stem cell proliferation is necessary for the continuous and reproducible development of plant organs1,2. The peptide ligand CLAVATA3 (CLV3) and its receptor protein kinase CLAVATA1 (CLV1) maintain stem cell homeostasis within a deeply conserved negative feedback circuit1,2. In Arabidopsis, CLV1 paralogs also contribute to homeostasis, by compensating for the loss of CLV1 through transcriptional upregulation3. Here, we show that compensation4,5 operates in diverse lineages for both ligands and receptors, but while the core CLV signaling module is conserved, compensation mechanisms have diversified. Transcriptional compensation between ligand paralogs operates in tomato, facilitated by an ancient gene duplication that impacted the domestication of fruit size. In contrast, we found little evidence for transcriptional compensation between ligands in Arabidopsis and maize, and receptor compensation differs between tomato and Arabidopsis. Our findings show that compensation among ligand and receptor paralogs is critical for stem cell homeostasis, but that diverse genetic mechanisms buffer conserved developmental programs.


Assuntos
Meristema/citologia , Meristema/genética , Desenvolvimento Vegetal/genética , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proliferação de Células/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genes de Plantas , Peptídeos e Proteínas de Sinalização Intercelular/genética , Ligantes , Lycopersicon esculentum/citologia , Lycopersicon esculentum/genética , Lycopersicon esculentum/crescimento & desenvolvimento , Modelos Genéticos , Mutação , Plantas Geneticamente Modificadas , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Células-Tronco/citologia , Zea mays/citologia , Zea mays/genética , Zea mays/crescimento & desenvolvimento
15.
Nat Plants ; 5(4): 352-357, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30936436

RESUMO

Meristem fate is regulated by trehalose 6-phosphate phosphatases (TPPs), but their mechanism of action remains mysterious. Loss of the maize TPPs RAMOSA3 and TPP4 leads to reduced meristem determinacy and more inflorescence branching. However, analysis of an allelic series revealed no correlation between enzymatic activity and branching, and a catalytically inactive version of RA3 complements the ra3 mutant. Together with their nuclear localization, these findings suggest a moonlighting function for TPPs.


Assuntos
Meristema/metabolismo , Monoéster Fosfórico Hidrolases/fisiologia , Proteínas de Plantas/fisiologia , Zea mays/crescimento & desenvolvimento , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Meristema/enzimologia , Meristema/crescimento & desenvolvimento , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas de Plantas/metabolismo , Zea mays/metabolismo
16.
Nature ; 568(7753): 511-516, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30971826

RESUMO

Functional genomics approaches can overcome limitations-such as the lack of identification of robust targets and poor clinical efficacy-that hamper cancer drug development. Here we performed genome-scale CRISPR-Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritize new targets in defined tissues and genotypes. We verified one of our most promising dependencies, the Werner syndrome ATP-dependent helicase, as a synthetic lethal target in tumours from multiple cancer types with microsatellite instability. Our analysis provides a resource of cancer dependencies, generates a framework to prioritize cancer drug targets and suggests specific new targets. The principles described in this study can inform the initial stages of drug development by contributing to a new, diverse and more effective portfolio of cancer drug targets.

17.
Mol Pharm ; 16(5): 2037-2047, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-30924661

RESUMO

Targeted delivery of otherwise nonimmunogenic antigens to Toll-like receptors (TLRs) expressed on dendritic cells (DCs) has proven to be an effective means of improving immunogenicity. For this purpose, we have used a branched cationic lipopeptide, R4Pam2Cys, which is an agonist for TLR2 and enables electrostatic association with antigen for this purpose. Here, we compare the immunological properties of ovalbumin formulated with different geometrical configurations of R4Pam2Cys. Our results demonstrate that notwithstanding the presence of the same adjuvant, branched forms of R4Pam2Cys are more effective at inducing immune responses than are linear geometries. CD8+ T-cell-mediated responses are particularly improved, resulting in significantly higher levels of antigen-specific cytokine secretion and cytolysis of antigen-bearing target cells in vivo. The results correlate with the ability of branched R4Pam2Cys conformations to encourage higher levels of DC maturation and facilitate superior antigen uptake, leading to increased production of proinflammatory cytokines. These differences are not attributable to particle size because both branched and linear lipopeptides associate with antigen-forming complexes of similar size, but rather the ability of branched lipopeptides to induce more efficient TLR2-mediated cell signaling. Branched lipopeptides are also more resistant to trypsin-mediated proteolysis, suggesting greater stability than their linear counterparts. The branched lipopeptide facilitates presentation of antigen more efficiently to CD8+ T cells, resulting in rapid cell division and upregulation of early cell surface activation markers. These results as well as cognate recognition of Pam2Cys by TLR2 indicate that the adjuvant's efficiency is also dependent on its geometry.

18.
Invest Ophthalmol Vis Sci ; 60(4): 1050-1062, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30897620

RESUMO

Purpose: We recently reported that the glycosaminoglycan hyaluronan (HA), which promotes inflammatory angiogenesis in other vascular beds, is an abundant component of the limbal extracellular matrix. Consequently, we have explored the possibility that HA contributes to lymphangiogenesis in the inflamed cornea. Methods: To study the role of HA on lymphangiogenesis, we used mice lacking the hyaluronan synthases and injury models that induce lymphangiogenesis. Results: Here we report that HA regulates corneal lymphangiogenesis, both during post-natal development and in response to adult corneal injury. Furthermore, we show that injury to the cornea by alkali burn upregulates both HA production and lymphangiogenesis and that these processes are ablated in HA synthase 2 deficient mice. Conclusion: These findings raise the possibility that therapeutic blockade of HA-mediated lymphangiogenesis might prevent the corneal scarring and rejection that frequently results from corneal transplantation.


Assuntos
Ácido Hialurônico/fisiologia , Limbo da Córnea/metabolismo , Linfangiogênese/fisiologia , Vasos Linfáticos/fisiologia , Animais , Queimaduras Químicas/fisiopatologia , Proliferação de Células , Sobrevivência Celular , Células Endoteliais/efeitos dos fármacos , Queimaduras Oculares/induzido quimicamente , Ácido Hialurônico/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Reação em Cadeia da Polimerase em Tempo Real , Hidróxido de Sódio
19.
Front Immunol ; 10: 471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30923528

RESUMO

The lymphatics fulfill a vital physiological function as the conduits through which leucocytes traffic between the tissues and draining lymph nodes for the initiation and modulation of immune responses. However, until recently many of the molecular mechanisms controlling such migration have been unclear. As a result of careful research, it is now apparent that the process is regulated at multiple stages from initial leucocyte entry and intraluminal crawling in peripheral tissue lymphatics, through to leucocyte exit in draining lymph nodes where the migrating cells either participate in immune responses or return to the circulation via efferent lymph. Furthermore, it is increasingly evident that most if not all leucocyte populations migrate in lymph and that such migration is not only important for immune modulation, but also for the timely repair and resolution of tissue inflammation. In this article, I review the latest research findings in these areas, arising from new insights into the distinctive ultrastructure of lymphatic capillaries and lymph node sinuses. Accordingly, I highlight the emerging importance of the leucocyte glycocalyx and its novel interactions with the endothelial receptor LYVE-1, the intricacies of endothelial chemokine secretion and sequestration that direct leucocyte trafficking and the significance of the process for normal immune function and pathology.

20.
Int J Pharm Pract ; 27(5): 451-458, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30790364

RESUMO

OBJECTIVES: (1) To identify any demographic characteristics, which predict medicines adherence by reporting Necessity-Concern Differential (NCD) and Self-Reported Health (SRH) scores among Hong Kong hospital outpatients. (ii) To investigate any association between SRH and NCD in this cultural group. METHODS: A total of 709 outpatients completed a questionnaire consisting demographic information, SRH and Belief about Medicines Questionnaire. Findings were analysed statistically. KEY FINDINGS: Descriptive statistics suggested that older participants (mean age > 64 years) tended to report low SRH, but high NCD compared to younger respondents (mean age < 53 years). Males were more likely to return high SRH and NCD scores than females (56.9 versus 42.2% and 74.8 versus 64.6%, respectively). Chi-squared tests demonstrated that socio-economic status was not significantly associated with SRH and NCD reporting (P > 0.05). Logistic regressions indicated gender and age groups (young-old and old-old) were significant predictors of SRH reporting (P < 0.001). Moreover, patients with high SRH were more likely to report high NCD than those with low SRH (P = 0.02; OR = 1.53; 95%CI 1.07-2.20). This indicates that regular administration of the SRH item followed by specific questioning could enhance early identification of potential medicine non-believers and, subsequently, non-adherent patients who may require urgent interventions or monitoring. CONCLUSIONS: Demographic characteristics and significant association between SRH and NCD reporting support our claim that SRH opens new opportunities for prompt identification of potentially non-adherent patients. However, further interviews to determine the cause(s) of non-adherence are necessary to validate such findings.

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