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BACKGROUND/AIMS: Information regarding the use of wearable devices in clinical research, including disease areas, intervention techniques, trends in device types, and sample size targets, remains elusive. Therefore, we conducted a comprehensive review of clinical research trends related to wristband wearable devices in research planning and examined their applications in clinical investigations. METHODS: As this study identified trends in the adoption of wearable devices during the planning phase of clinical research, including specific disease areas and targeted number of intervention cases, we searched ClinicalTrials.gov-a prominent platform for registering and disseminating clinical research. Since wrist-worn devices represent a large share of the market, we focused on wrist-worn devices and selected the most representative models among them. The main analysis focused on major wearable devices to facilitate data analysis and interpretation, but other wearables were also surveyed for reference. We searched ClinicalTrials.gov with the keywords "ActiGraph,""Apple Watch,""Empatica,""Fitbit,""Garmin," and "wearable devices" to obtain studies published up to 21 August 2022. This initial search yielded 3214 studies. After excluding duplicate National Clinical Trial studies (the overlap was permissible among different device types except for wearable devices), our analysis focused on 2930 studies, including simple, time-series, and type-specific assessments of various variables. RESULTS: Overall, an increasing number of clinical studies have incorporated wearable devices since 2012. While ActiGraph and Fitbit initially dominated this landscape, the use of other devices has steadily increased, constituting approximately 10% of the total after 2015. Observational studies outnumbered intervention studies, with behavioral and device-based interventions being particularly prevalent. Regarding disease types, cancer and cardiovascular diseases accounted for approximately 20% of the total. Notably, 114 studies adopted multiple devices simultaneously within the context of their clinical investigations. CONCLUSIONS: Our findings revealed that the utilization of wearable devices for data collection and behavioral interventions in various disease areas has been increasing over time since 2012. The increase in the number of studies over the past 3 years has been particularly significant, suggesting that this trend will continue to accelerate in the future. Devices and their evaluation methods that have undergone thorough validation, confirmed their accuracy, and adhered to established legal regulations will likely assume a pivotal role in evaluations, allowing for remote clinical trials. Moreover, behavioral intervention therapy utilizing apps is becoming more extensive, and we expect to see more examples that will lead to their approval as programmed medical devices in the future.
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Dispositivos Eletrônicos Vestíveis , Humanos , Pesquisa Biomédica , Ensaios Clínicos como Assunto , PunhoRESUMO
Antipsychotic medications increase the risk of abnormal glucose metabolism. However, in clinical practice, it is difficult to predict this risk because it is affected by medication-related and background factors. This study aimed to identify the risk factors for abnormal glucose metabolism during antipsychotic treatment. We conducted a multicenter, prospective, cohort study in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, those with prediabetes or possible diabetes were excluded. Finally, 706 patients were included in the analysis. The hazard ratio (HR) for each factor was calculated for events of progression to hyperglycemia using time-dependent Cox regression analysis stratified according to facility type and adjusted for available background and drug-related factors. Treatments with olanzapine (HR = 2.06, 95% confidence interval [CI] = 1.05-4.05), clozapine (HR = 4.25, 95% CI = 1.56-11.60), and chlorpromazine (HR = 4.48, 95% CI = 1.21-16.57), overweight and obesity (HR = 1.57, 95% CI = 1.02-2.41), and hypertriglyceridemia (HR = 1.72, 95% CI = 1.02-2.88) were associated with a significantly higher occurrence of hyperglycemic progression. The number and daily dose of antipsychotics were not associated with their occurrence. Our study demonstrated that more careful monitoring is necessary during olanzapine, clozapine, and chlorpromazine treatment because of the higher occurrence of abnormalities in glucose metabolism. Furthermore, patients with obesity or hypertriglyceridemia warrant monitoring for the occurrence of abnormal glucose metabolism, regardless of the type of antipsychotic medication.
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Antipsicóticos , Clozapina , Hipertrigliceridemia , Humanos , Antipsicóticos/efeitos adversos , Olanzapina/efeitos adversos , Clozapina/uso terapêutico , Estudos Prospectivos , Estudos de Coortes , Glucose , Clorpromazina , Benzodiazepinas/efeitos adversos , Fatores de Risco , Obesidade/induzido quimicamente , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/tratamento farmacológicoRESUMO
INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.
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Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Estenose Espinal , Humanos , Estudos Prospectivos , Medula Óssea , Constrição Patológica , Degeneração do Disco Intervertebral/cirurgia , Estenose Espinal/cirurgia , Canal Medular , Resultado do Tratamento , Vértebras Lombares/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a mitochondrial fatty acid oxidation disorder that causes episodic attacks, such as general fatigue, hypotonia, myalgia, and rhabdomyolysis accompanied by lack of energy. As yet, there are no preventative drugs for these VLCADD-associated metabolic attacks. PATIENTS AND METHODS: We conducted an open-label, non-randomized, multi-center study into the effects of bezafibrate on five patients with VLCADD. Bezafibrate was administered for 4 years, and we analyzed the number of myopathic attacks requiring hospitalization and treatment infusions. RESULTS: The number of myopathic attacks requiring infusions of 24 h or longer significantly decreased during the study period. The patients' ability to conduct everyday activities was also improved by the treatment. CONCLUSION: Our findings show the potential long-term efficacy of bezafibrate in preventing myopathic attacks for patients with VLCADD.
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Bezafibrato/uso terapêutico , Síndrome Congênita de Insuficiência da Medula Óssea/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Doenças Mitocondriais/tratamento farmacológico , Doenças Musculares/tratamento farmacológico , Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Acil-CoA Desidrogenase de Cadeia Longa/genética , Adulto , Bezafibrato/metabolismo , Criança , Síndrome Congênita de Insuficiência da Medula Óssea/fisiopatologia , Feminino , Humanos , Erros Inatos do Metabolismo Lipídico/fisiopatologia , Masculino , Doenças Mitocondriais/fisiopatologia , Doenças Musculares/fisiopatologiaRESUMO
INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by a defective mitochondrial fatty acid oxidation (FAO) enzyme. We recently reported that bezafibrate improved patient quality of life (QOL) based on the SF-36 questionnaire score in patients with FAODs during a 50-week, open-label, clinical trial. Herein we conducted further survey assessments of the trial patients to define the long-term efficacy and safety of bezafibrate. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in five patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and one patient with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 15.9â¯years; range, 5.8-26.4â¯years). The bezafibrate administration was continued for a further 102-174â¯weeks after the 24-week treatment described in our previous study. QOL was quantitated using the 36-Item Short Form Health Survey (SF-36) questionnaire, which constitutes eight components: physical functioning (PF), role limitation due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. RESULTS: PF was elevated in all patients and continued to rise during the study, with the total QOL scores increased from baseline in five of the six cases. In particular, three patients older than 20â¯years showed treatment efficacy, and all subcategories of QOL were elevated in two of these cases. CONCLUSION: Our findings supported one of the stated benefits of bezafibrate in improving QOL for patients with FAODs.
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The prognosis of advanced pancreatic adenocarcinoma is still extremely poor. This study sought to determine the efficacy of, and immunological response to, peptide vaccination therapy in patients with this disease. In this multicenter randomized phase II study, patients with advanced pancreatic adenocarcinoma after gemcitabine and/or tegafur/gimeracil/oteracil were randomly assigned to 3 groups that each received a 2-step treatment course. In Step 1, the groups received treatments of: (i) survivin 2B peptide (SVN-2B) plus interferon-ß (IFNß); (ii) SVN-2B only; or (iii) placebo until the patients show progression. In Step 2, all patients who consented to participate received 4 treatments with SVN-2B plus IFNß. The primary endpoint was progression-free survival (PFS) after initiation of Step 1 treatment. Secondary endpoints included immunological effects assessed by analysis of PBMCs after Step 1. Eighty-three patients were randomly assigned to receive SVN-2B plus IFNß (n = 30), SVN-2B (n = 34), or placebo (n = 19). No significant improvement in PFS was observed. Survivin 2B-specific CTLs were found to be increased in the SVN-2B plus IFNß group by tetramer assay. Among patients who participated in Step 2, those who had received SVN-2B plus IFNß in Step 1 showed better overall survival compared with those who had received placebo in Step 1. Patients vaccinated with SVN-2B plus IFNß did not have improved PFS, but showed significant immunological reaction after vaccination. Subgroup analysis suggested that a longer SVN-2B plus IFNß vaccination protocol might confer survival benefit. (Clinical trial registration number: UMIN 000012146).
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Adenocarcinoma/tratamento farmacológico , Vacinas Anticâncer/uso terapêutico , Interferon beta/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos/uso terapêutico , Survivina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Vacinação/métodos , Vacinas de Subunidades Antigênicas/uso terapêutico , Gencitabina , Neoplasias PancreáticasRESUMO
INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2â¯years; ranging from 5.8 to 26.4â¯years). Bezafibrate was administered for 6â¯months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16â¯+â¯C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). RESULTS: The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. CONCLUSION: In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations.
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Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic "blood lakes" in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas.
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Epitope retrieval (ER) using heating causes a dramatic improvement in the sensitivity of immunohistochemistry for formalin-fixed paraffin-embedded (FFPE) tissue sections. Here, the relationship between the pH of the retrieval buffer used for heat-induced epitope retrieval (HIER) and the isoelectric points (pI) of the antigen recognized by antibodies against nuclear proteins (mainly human pituitary transcription factors in this study) was investigated using FFPE tissue sections. A universal buffer, with a buffering capacity over a wide pH range from 2.0 to 12.0, was used for HIER. We found that the intensity of staining for most nuclear proteins after HIER depended simply on the pH of the buffer. Importantly, for efficient HIER, antigens with acidic pI required basic pH buffer conditions, while antigens with alkaline pI required acidic conditions. This implies that the electrostatic charge of the antigens contributed significantly to the efficiency of HIER. We conclude that appropriate selection of the pH of the buffer based on the pI of the individual antigens is of great importance for efficient ER. It is concluded that the mechanism of HEIR may, therefore, depend to a large extent on the pI of the antigen under investigation.
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Epitopos/análise , Imuno-Histoquímica/métodos , Anticorpos , Antígenos , Soluções Tampão , Formaldeído , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Imuno-Histoquímica/normas , Ponto Isoelétrico , Proteínas Nucleares/análise , Proteínas Nucleares/imunologia , Inclusão em Parafina , Fixação de TecidosRESUMO
Growth hormone (GH)-producing adenomas (GHomas) are one of the most frequently-occurring pituitary adenomas. Differentiation of hormone-producing cells in the pituitary gland is regulated by transcription factors and co-factors. The transcription factors include Pit-1, Prop-1, NeuroD1, Tpit, GATA-2, SF-1. Aberrant expression of transcription factors such as Pit-1 results in translineage expression of GH in adrenocorticotropic hormone-producing adenomas (ACTHomas). This situation has been substantiated by GFP-Pit-1 transfection expression in the AtT20 cell line. Experimentally, GHomas have been induced in GH-releasing hormone (GHRH) or Prop-1 transgenic animals. Immunohistochemical detection of somatostatin receptor (SSTR2a) has recently emphasized their role in the response of GHomas to somatostatin analogue therapy. In this review, the advances in technology and their contribution to cell biology and medical practice are discussed.
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Bisphenol A (BPA) is a monomer use in manufacturing a wide range of chemical products which include epoxy resins and polycarbonate. It has been reported that BPA increases the cell proliferation activity of human breast cancer MCF-7 cells as well as 17-beta estradiol (E2) and diethylstilbestrol (DES). However, BPA induces target genes through ER-dependent and ER-independent manners which are different from the actions induced by E2. Therefore, BPA may be unique in estrogen-dependent cell proliferation compared to other endocrine disrupting chemicals (EDCs). In the present study, to test whether ERalpha is essential to the BPA-induced proliferation on MCF-7 cells, we suppressed the ERalpha expression of MCF-7 cells by RNA interference (RNAi). Proliferation effects in the presence of E2, DES and BPA were not observed in ERalpha-knockdown MCF-7 cells in comparison with control MCF-7. In addition, a marker of proliferative potential, MIB-1 labeling index (LI), showed no change in BPA-treated groups compared with vehicle-treated groups on ERalpha-knockdown MCF-7 cells. In conclusion, we demonstrated that ERalpha has a role in BPA-induced cell proliferation as well as E2 and DES. Moreover, this study indicated that the direct knockdown of ERalpha using RNAi serves as an additional tool to evaluate, in parallel with MCF-7 cell proliferation assay, for potential EDCs.
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Wnt signaling is important in many aspects of cell biology and development. In the mouse female reproductive tract, Wnt4, Wnt5a, and Wnt7a show differential expression during the estrus cycle, suggesting that they participate in female reproductive physiology. Although the pituitary is a major gland regulating reproduction, the molecular mechanism of Wnt signaling here is unclear. We elucidated the subcellular distribution of Wnt4 in the pituitary of estrogen-treated ovariectomized female rats. Expression of Wnt4 mRNA increased dramatically, particularly in proestrus compared with estrus and metestrus. Wnt4 protein was observed in the cytoplasm of almost all growth hormone (GH)-producing cells and in only a few thyroid-stimulating hormone beta (TSHbeta)-producing cells. In rat GH-producing pituitary tumor (MtT/S) cells, estrogen-induced expression of Wnt4 mRNA was completely inhibited by estrogen receptor antagonist ICI 182,780 in vitro. Thus, rat pituitary GH cells synthesize Wnt4 and this is induced by estrogen mediated via an estrogen receptor alpha-dependent pathway.
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The Wnt signaling pathway has been implicated in the genesis of numerous human cancers. A member of the Wnt family of genes, Wnt4, has been known to regulate proliferation of anterior pituitary cell types in the mouse during embryonic development. In order to elucidate the roles of Wnt signaling in human pituitary adenomas, we examined the expression of Wnt4 and its putative receptor Frizzled6 (Fzd6) by immunohistochemistry in pituitary adenomas and normal pituitaries. Expression of Wnt4 was higher in growth hormone-producing adenomas (GHomas), prolactin-producing adenomas (PRLomas), and thyroid-stimulating hormone-producing adenomas (TSHomas) than in the normal pituitary. Fzd6 was widely expressed in GHomas, PRLomas, TSHomas, and gonadotropin subunit (GnSU)-positive adenomas. In normal pituitary glands, Wnt4 and Fzd6 were colocalized predominantly in follicle-stimulating hormone-, luteinizing hormone-, and alpha-subunits of glycoprotein hormone-positive cells. The canonical Wnt/beta-catenin signaling pathway was analyzed by beta-catenin immunohistochemistry. beta-Catenin was localized at the cell membrane in all pituitary adenomas, but not in the nuclei. On the other hand, Erk1/2 was highly activated in GHomas and TSHomas. These results suggested that activation of Wnt4/Fzd6 signaling through a "beta-catenin-independent" pathway played a role in proliferation and survival of the pituitary adenoma cells. Detailed involvement of transcription factors including Pit-1 remains to be further investigated.
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Adenoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Hipofisárias/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Adenoma/genética , Adenoma/patologia , Adolescente , Adulto , Idoso , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genética , Proteínas Wnt/genética , Proteína Wnt4 , Adulto Jovem , beta Catenina/genéticaRESUMO
OBJECTIVE: The aim of this study was to determine the correlation between the expression of somatostatin receptors by immunohistochemistry and the percent suppression of GH levels in the octreotide suppression test. PATIENTS AND METHODS: Twenty-two patients with acromegaly who underwent an octreotide suppression test before surgery were studied. We performed immunohistochemistry for Somatostatin receptor 2A (SSTR2A) and Somatostatin receptor 5 (SSTR5) on the surgical specimens from all patients, which we scored according to the number of tumor cells staining positive at the surface membrane (3+: >50%, 2+: 25-50%, 1+: <25%). We sought correlations of percent suppression in the octreotide suppression test with these immunohistochemistry scores. RESULTS: Somatostatin receptor 2A (SSTR2A) showed the highest frequency of score 3+ (13 of 22, 59.1%) by immunohistochemistry. Subtype 5 showed the highest frequency for score 2+ (9 of 22, 40.9%), and one (4.5%) was immunonegative. For subtype 2A, there was a significant correlation with percent decrease (P = 0.002 < 0.01). In contrast, there was no significant correlation for SSTR5. CONCLUSION: Immunohistochemistry for SSTR2A in pathology specimens from acromegalic patients enabled selection of those experiencing clinical benefit from octreotide. Therefore, performing immunohistochemistry for detection of SSTR2A is recommended for all specimens obtained by surgery.
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Adenoma/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Octreotida/uso terapêutico , Receptores de Somatostatina/biossíntese , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Adenoma/tratamento farmacológico , Adulto , Idoso , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Terapia NeoadjuvanteRESUMO
Immunological memory induced by nasal immunization with adjuvant-combined influenza vaccine was analyzed in different ages and strains of mice. The memory activities were assessed by secondary nasal-wash IgA and serum IgG antibody (Ab) responses and protection against challenge infection with a lethal dose of influenza virus. Mice were primed with 0.1 microg of vaccine and boosted with 0.1 or 1.0 microg vaccine 1 (short-term memory)- or 17 (long-term memory)-months later. Influenza-specific short-term memory responses in young adult BALB/c mice (2-month-old) were significantly higher than those of long-term memory activities in mice boosted at 19 months of age. However, those influenza-specific long-term memory responses provided protective immunity against influenza virus challenge and were higher than short-term memory in aged mice primed at 18-month-old and boosted 1 month later. These results show that the age at which initial nasal immunization is given is critically important in order to induce protective immunity in aged mice. Similar findings were noted in the C3H mouse strain; however, C57BL/6 mice failed to induce influenza-specific immune responses in both young adult and aged mice. These results indicate that low doses of cholera toxin B subunit (supplemented with 0.2% of hole toxin) combined nasal vaccine may required further improvement in order to provide protective immunity in human use.
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Adjuvantes Imunológicos/administração & dosagem , Envelhecimento/imunologia , Anticorpos Antivirais/sangue , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Memória Imunológica , Vacinas contra Influenza/imunologia , Administração Intranasal , Animais , Linhagem Celular , Feminino , Imunidade nas Mucosas , Imunoglobulina A Secretora/análise , Imunoglobulina G/sangue , Vacinas contra Influenza/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Especificidade da Espécie , Fatores de TempoRESUMO
Alkylphenol ethoxylates, widely used non-ionic surfactants, are biodegraded into alkylphenols such as nonylphenol (NP) and t-octylphenol (OP), short-chain ethoxylates such as NP-monoethoxylate (NP1EO) and NP-diethoxylate (NP2EO), and alkylphenoxy carboxylic acids such as 4-t-octylphenoxyacetic acid (OP1EC). Bisphenol S (BPS) is more heat-stable and photo-resistant than bisphenol A (BPA), and therefore replaces BPA. These chemicals could be chlorinated during wastewater treatment. We synthesized these compounds and their chlorinated derivatives to estimate their estrogenic activities using a GFP expression system. The EC(50) ranking of NP-related compounds was NP > ClNP > diClNP > NP1EO > ClNP1EO > NP2EO. The estrogenic activity of OP1EC was 10 times less potent than parent OP. Furthermore, BPS showed comparable estrogenic activity with BPA. The EC(50) ranking of BPS-related compounds was BPA ≥ BPS > triClBPS > diClBPS > ClBPS. Other tested BPS derivatives had no estrogenic activity. Chlorination of the tested chemicals did not enhance their estrogenic activity, in contrast to certain chlorinated BPAs. Thus, our results demonstrated that chlorinated derivatives of NP, OP, and BPS, even if artificially produced during wastewater processing, were less estrogenic than their parent chemicals, known as endocrine disruptors.