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1.
Ultrastruct Pathol ; 48(5): 378-421, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39105605

RESUMO

INTRODUCTION: Xenografts of androgen-independent human DU145 prostate metastatic carcinomas implanted in nu/nu male mice have revealed a significant survival after a prooxidant anticancer treatment consisting of a combination of menadione bisulfite and sodium ascorbate (VK3:VC). METHODS: Implanted samples of diaphragm carcinomas from longest survived mice from either oral, intraperitoneal (IP), or both oral and IP treatment groups were assessed with light, scanning, and transmission electron microscopy to analyze morphologic damages. RESULTS: Compared with previous fine structure data of in vitro untreated carcinomas, the changes induced by oral, IP, and oral with IP VK3:VC treatment dismantled those xenografts with autoschizis, and necrotic atrophy was accomplished by cell's oxidative stress whose injuries were consequent to reactivated deoxyribonucleases and ribonucleases. Tumor destructions resulted from irreversible damages of nucleus components, endoplasmic reticulum, and mitochondria there. Other alterations included those of the cytoskeleton that resulted in characteristic self-excisions named " autoschizis." All these injuries lead resilient cancer cells to necrotic cell death. CONCLUSION: The fine structure damages caused by VK3:VC prooxidant combination in the human DU145 prostate xenografts confirmed those shown in vitro and of other cell lines with histochemistry and biomolecular investigations. These devastations incurred without damage to normal tissues; thus, our data brought support for the above combination to assist in the treatment of prostate cancers and other cancers.


Assuntos
Ácido Ascórbico , Camundongos Nus , Neoplasias da Próstata , Vitamina K 3 , Masculino , Humanos , Animais , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Ácido Ascórbico/farmacologia , Camundongos , Vitamina K 3/farmacologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Estresse Oxidativo/efeitos dos fármacos , Microscopia Eletrônica de Transmissão
2.
Ultrastruct Pathol ; 46(5): 413-438, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36165802

RESUMO

Human prostate carcinoma DU145 cells, androgen-independent malignant cells, implanted in the athymic nu/nu male mouse, developed numerous tumors on peritoneal and retro-peritoneal organs whose growth aspects and vascular supply have yet to be investigated with fine structure techniques. A series of necropsies from moribund implanted mice diaphragms were examined with light, scanning, and transmission electron microscopy. DU145 xenografts installations, far away from the implanted site, were described as the smallest installation to large diaphragm outgrowths in moribund mice. Carcinomas did not show extracellular matrix and, reaching more than 0.15 mm in thickness, they revealed new structures in these outgrowths. Voids to be gland-like structures with mediocre secretion and, unexpectedly, intercellular spaces connected with fascicles of elongated DU145 cells that merged with a vascular supply originated from either the tumor cells and/or some perimysium vessels. In the largest carcinomas, most important vascular invasions coincidently accompanied the mouse lethality, similarly to human cancers. This androgen-independent model would be useful to study tumor outgrowth's changes related to testing anticancer strategy, including anti-angiogenic therapies involving toxicity, simultaneously with those of other vital organs with combined biomolecular and fine structure techniques.


Assuntos
Carcinoma , Neoplasias da Próstata , Androgênios , Animais , Linhagem Celular Tumoral , Diafragma/patologia , Epitélio/patologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Próstata/patologia , Neoplasias da Próstata/patologia
3.
Adv Physiol Educ ; 46(3): 498-506, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796466

RESUMO

There is extensive and increasing use of ultrasound in medical care and scientific research, so it is important that the technique, indication, and interpretation of ultrasound investigations are included in medical and biological education. Applications of ultrasound in medical care and education employ not only noninvasive imaging of structure but also the evaluation of organ function. Vascular ultrasound is one such application that has been hitherto relatively neglected in physiology education. The techniques of vascular ultrasound and the physiological regulation of human limb blood flow are reviewed to inform students and curriculum designers. Emphasis is placed on the value of converting velocity measurement by ultrasound to volumetric flow and on the mechanisms involved in rapidly changing flows with interventions. Live collection of real data by ultrasound can show macrovascular and microvascular features of vascular physiology. Macrovascular features include imaging and flow velocity profiles. Microvascular perfusion studies show conductance changes with interventions such as exercise and ischemia. Vascular ultrasound offers exciting opportunities for undergraduate research projects using human subjects. The literature is interesting and, though complex, offers excellent educational experience, with scope for the development of critical thinking and meaningful original research.NEW & NOTEWORTHY Ultrasound imaging has emergent prominence in clinical investigation and education. Vascular ultrasound also evaluates function. Simple methods are described that enable the application of basic ultrasound principles to the measurement of velocity and, importantly, to calculate absolute volumetric blood flow. These methods should be useful in undergraduate and graduate education, with application in clinical practice and research.


Assuntos
Artéria Braquial , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiologia , Humanos , Ultrassonografia
4.
Bioorg Med Chem Lett ; 26(18): 4451-4454, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27515319

RESUMO

This paper describes the development of novel anticancer poly-hydroxylated tolans. Based on structural similarity to resveratrol, a series of hydroxytolans were synthesized and evaluated for their antitumor capability against three tumor cell lines and one fibroblast cell line for selectivity comparisons. The 4,4'-dihydroxytolan (KST-201) exhibited the most significant anticancer activity with increased selectivity when compared to resveratrol and other hydroxytolans. Unlike resveratrol, KST-201 can boost hydrogen peroxide in tumor cells, which are often at high basal level of reactive oxygen species, to cause cell death by overwhelming the cellular tolerance of oxidative stress.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos
5.
Nicotine Tob Res ; 18(5): 1054-60, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26453668

RESUMO

INTRODUCTION: Smoking cessation support is increasingly delivered in primary care by auxiliary healthcare workers in place of healthcare professionals. However, it is unknown whether this shift might affect the quality and impact of the support delivered. METHODS: Data from the iQuit in Practice randomized control trial of cessation support in General Practice was used (N = 602). Analyses assessed whether cessation advisor type (nurse or healthcare assistant [HCA]) was associated with abstinence (primary outcome: self-reported 2-week point prevalence abstinence at 8 weeks follow-up), the advice delivered during the initial consultation, pharmacotherapies prescribed, patient satisfaction, initial consultation length, and the number and type of interim contacts. RESULTS: There were no statistically significant differences in abstinence for support delivered by HCAs versus nurses at 8 weeks (HCAs 42.8%, nurses 42.6%; unadjusted odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.73 to 1.40), or at 4 weeks or 6 months follow-up. There were no statistically significant differences in advice delivered, the types of pharmacotherapies prescribed or patient satisfaction. Compared with nurses, HCA consultations were longer on average (HCAs 23.6 minutes, nurses 20.8 minutes; P = .002) and they undertook more interim contacts (HCAs median 2, nurses median 1; P < .001), with contact more likely to be face-to-face than phone call (HCAs 91.2%, nurses 70.9%; OR = 4.23, 95% CI = 2.86 to 6.26). CONCLUSIONS: HCAs appear equally effective as nurses in supporting smoking cessation, although they do this with greater patient contact. Using auxiliary practitioners to deliver cessation support could free up nurse time and reduce costs. IMPLICATIONS: This study found that primary care patients receiving smoking cessation support from auxiliary healthcare workers were just as likely to be abstinent up to 6 months later as those patients seen by nurses. While the auxiliary healthcare workers achieved this with slightly increased patient contact time, the advice delivered, pharmacotherapies provided and patient satisfaction were similar to that of nurses. Expanding the auxiliary healthcare worker role to include smoking cessation support could increase role satisfaction and reduce the costs of cessation support delivery in primary care.


Assuntos
Pessoal Técnico de Saúde , Recursos Humanos de Enfermagem , Atenção Primária à Saúde/métodos , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Adulto , Feminino , Humanos , Masculino , Satisfação do Paciente , Encaminhamento e Consulta
6.
Ultrastruct Pathol ; 40(5): 231-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27163289

RESUMO

Ultrastructural data compiled from DU145 human prostate carcinoma cells growing in vivo and, more often in vitro or after treatment by pro-oxidant reactants, can induce and encompass several processes of cell internalization or entosis. These events were observed after tumor cells were essentially undergoing autoschizic injuries and other cell deaths without externalization of phosphatidylserine. Based on other previous observations made on DU145 cells, one hypothesizes that, as a means of survival, tumor cells find sources of nutrients through phagocytosis of apparently intact, injured cells, corpses, and cell debris by cannibalism. These peculiar activities occurred sporadically, in a small population of cells and could be dictated by their widely adapted energetic metabolism, now impaired, either due to the location of the cells in the growing tumors or in vitro as a result of this pro-oxidant anticancer treatment causing damage and abolishing their adapted metabolism.


Assuntos
Entose/fisiologia , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Transmissão
7.
Ultrastruct Pathol ; 40(4): 189-99, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27044781

RESUMO

The intracellular or intracytoplasmic lumen (IL) is an enigmatic histological structure that occurs in various tumor cells. A reassessment of diverse ILs fine-structure micrographs obtained out of previous studies encompassing the human prostate carcinoma (DU145) cell line and xenotransplanted carcinomas enabled us to propose aspects of ILs development in cancer cells: a combination of altered expressions in intercellular contacts and their cytoskeletal components would favor a disarray of self-apical polarity orientation; those defects, associated with a local, entwined enriched membranous structures growing as microvilli-like formations out of a disrupted endoplasm and trans-Golgi sorting, create ILs in cells' perikarya. These misplaced intracytoplasmic domains can become enlarged through spaces made between the finger-like structures by accruing membranes of coalescent intracytoplasmic vesicles then adding microvilli and glycocalyx to constitute ILs. Cationic mucins added with or without a progressive or total loss of microvilli and content generate signet or ring cell, while ILs enlarge. Variable build-ups of these cells' populations in carcinomas result in architectural mix-up of adjacent cells around these voids, misconstrued as new lumen, and establish a "cribriform" tumor pattern that often implies a poor cancer prognosis. Alternatively, cytotoxic changes caused by anticancer pro-oxidant treatment favor membrane alterations and exaggerate the ILs in xenotransplants into intracellular crypts that accompany other tumor degenerative changes.


Assuntos
Carcinoma/patologia , Carcinoma/ultraestrutura , Neoplasias da Próstata/patologia , Neoplasias da Próstata/ultraestrutura , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão
8.
Bioorg Med Chem Lett ; 25(19): 4158-63, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26299349

RESUMO

The observation that cholinergic deafferentation of circuits projecting from forebrain basal nuclei to frontal and hippocampal circuits occurs in Alzheimer's disease has led to drug-targeting of muscarinic M1 receptors to alleviate cognitive symptoms. The high homology within the acetylcholine binding domain of this family however has made receptor-selective ligand development challenging. This work presents the synthesis scheme, pharmacokinetic and structure-activity-relationship study findings for M1-selective ligand, LY593093. Pharmacologically the compound acts as an orthosteric ligand. The homology modeling work presented however will illustrate that compound binding spans from the acetylcholine pocket to the extracellular loops of the receptor, a common allosteric vestibule for the muscarinic protein family. Altogether LY593093 represents a growing class of multi-topic ligands which interact with the receptors in both the ortho- and allosteric binding sites, but which exert their activation mechanism as an orthosteric ligand.


Assuntos
Amidas/química , Amidas/farmacologia , Desenho de Fármacos , Receptor Muscarínico M1/agonistas , Amidas/síntese química , Animais , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Ratos , Relação Estrutura-Atividade
9.
Ultrastruct Pathol ; 38(5): 315-28, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24955925

RESUMO

One hour after pro-oxidative treatment by either ascorbate (VC), menadione (VK3), or VC: VK3 combination followed by 24-h incubation in culture medium, DU145 human prostate carcinoma cells developed ultrastructural-dependent organelle damage with the sequence Sham > VC > VK3 > VC: VK3. Along the nuclear alterations and the cytoplasm self-excisions reducing cell size, other induced injuries concerned mitochondria and endomembranes that associated with lysosomes. Damaged organelles surrounded by specialized endoplasmic membranes formed autophagosomes out of phagophores that also captured pieces of glycogen-rich cytoplasm. Most autophagosomes amassed in the diminished-size perikarya and corroborated the enhanced cytotoxicity of the VC: VK3 treatment. These accumulations did not initiate cell death, instead were merely signs of excessive "recycling" of damaged organelles. These features may reflect that high lysosomal activities provided foodstuffs in an ultimate strategy of survival of the tumor cells already devastated by reactive oxidative species (ROS) energetic sites. As such they became transient markers preceding cell death induced to occur by autoschizis and not by apoptosis or other cell deaths. This report could provide more support for the usage of this vitamin combination named APATONE as inexpensive potent adjuvant or treatment in prostate cancers.


Assuntos
Autofagia , Citoplasma/ultraestrutura , Mitocôndrias/ultraestrutura , Neoplasias da Próstata/patologia , Morte Celular , Linhagem Celular Tumoral , Humanos , Lisossomos/patologia , Masculino , Neoplasias da Próstata/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Vitamina K 3/metabolismo
10.
Ultrastruct Pathol ; 38(2): 116-40, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24460713

RESUMO

Scanning (SEM) and transmission electron microscopy (TEM) were used to characterize the cytotoxic effects of ascorbate (VC), menadione (VK3), or a VC:VK3 combination on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a subsequent 24-h incubation in culture medium. Cell alterations examined by light and electron microscopy were treatment-dependent with VC + VK3 >VK3 > VC > Sham. Oxidative stress-induced damage was found in most organelles. This report describes injuries in the tumor cell nucleus (chromatin and nucleolus), mitochondria, endomembranes, lysosomal bodies (autophagocytoses) and inclusions. Morphologic alterations suggest that cytoskeleton damage is likely responsible for the superficial cytoplasmic changes, including major changes in cell shape and size and the self-excising phenomena. Unlike apoptotic bodies, the excised pieces contain ribonucleoproteins, but not organelles. These deleterious events cause a progressive, significant reduction in the tumor cell size. During nuclear alterations, the nuclei maintain their envelope during chromatolysis and karyolysis until cell death, while nucleoli undergo a characteristic segregation of their components. In addition, changes in fat and glycogen storage are consistent the cytotoxic and metabolic alterations caused by the respective treatments. All cellular ultrastructural changes are consistent with cell death by autoschizis and not apoptosis or other kinds of cell death.


Assuntos
Adenocarcinoma/ultraestrutura , Ácido Ascórbico/farmacologia , Morte Celular/efeitos dos fármacos , Neoplasias da Próstata/ultraestrutura , Vitamina K 3/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/ultraestrutura , Humanos , Masculino , Microscopia Eletrônica , Organelas/efeitos dos fármacos , Organelas/ultraestrutura
11.
BJGP Open ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38649161

RESUMO

BACKGROUND: There is evidence that engaging in research is directly associated with better performance. If this relationship is to be strengthened, it is necessary to understand the mechanisms that might underlie that relationship. AIM: To explore the perspectives of staff and wider stakeholders about mechanisms by which research activity may impact on the performance of general practices. DESIGN & SETTING: Qualitative study using semi-structured interviews with general practice professionals and wider stakeholders in England. METHOD: Individual interviews with 41 purposively sampled staff in 'research-ready' or 'research-active' general practices, and 21 other stakeholders. Interviews were independently coded by three researchers using a framework approach. RESULTS: Participants described potential 'direct' and 'indirect' impacts on their work. 'Direct' impacts included improved knowledge and skills that could change practice work (for example, additional records searches for particular conditions); bringing in additional resources (for example, access to investigations or staff); and improving relationships with patients. 'Indirect' impacts included job satisfaction (for example, perception of practice as a centre of excellence and innovation, and the variety afforded by research activity reducing burnout); and staff recruitment (increasing the attractiveness of the practice as a place to work). Responders identified few negative impacts. CONCLUSION: Staff and stakeholders identified a range of potential impacts of research activity on practice performance, with impacts on their working lives most salient. Negative impacts were not generally raised. Nevertheless, responders generally discussed potential impacts rather than providing specific examples of those impacts. This may reflect the type of research activity conducted in general practice, often led by external collaborators.

12.
BMC Public Health ; 13: 324, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23575031

RESUMO

BACKGROUND: Primary care is an important setting for smoking cessation interventions. There is evidence for the effectiveness of tailored interventions for smoking cessation, and text messaging interventions for smoking cessation show promise. The intervention to be evaluated in this trial consists of two components: (1) a web-based program designed to be used by a practice nurse or other smoking cessation advisor (SCA); the program generates a cessation advice report that is highly tailored to relevant characteristics of the smoker; and (2) a three-month programme of automated tailored text messages sent to the smoker's mobile phone. The objectives of the trial are to assess the acceptability and feasibility of the intervention and to estimate the short-term effectiveness of the intervention in increasing the quit rate compared with usual care alone. METHODS/DESIGN: The design is a two parallel group randomised controlled trial (RCT). 600 smokers who want to quit will be recruited in up to 30 general practices in the East of England. During a consultation with an SCA, they will be individually randomised by computer program to usual care (Control) or to usual care plus the iQuit system (Intervention). At the four-week follow-up appointment, the SCA will record smoking status and measure carbon monoxide level. There will be two further follow-ups, at eight weeks and six months from randomisation date, by postal questionnaire sent from and returned to the study centre or by telephone interview conducted by a research interviewer. The primary outcome will be self-reported abstinence for at least two weeks at eight weeks. A sample size of 300 per group would give 80% power to detect an increase in quit rate from 20% to 30% (alpha = 0.05, 2-sided test). The main analyses of quit rates will be conducted on an intention-to-treat basis, making the usual assumption that participants lost to follow up are smoking. DISCUSSION: This trial will focus on acceptability, feasibility and short-term effectiveness. The findings will be used to refine the intervention and to inform the decision to proceed to a pragmatic trial to estimate longer-term effectiveness and cost-effectiveness. TRIAL REGISTRATION: ISRCTN56702353.


Assuntos
Atenção Primária à Saúde/métodos , Abandono do Hábito de Fumar/métodos , Adolescente , Adulto , Idoso , Protocolos Clínicos , Inglaterra , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e Questionários , Envio de Mensagens de Texto , Resultado do Tratamento , Adulto Jovem
13.
Health Educ Res ; 28(5): 911-22, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23640985

RESUMO

SMS text messaging shows promise for delivering smoking cessation support. However, little is known about smokers' feelings towards receiving behavioural advice and support on their mobile phones. This article explores the attitudes of women with experience of prenatal smoking towards receiving pregnancy-related smoking cessation support by text message. Data collected by semi-structured interviews and focus group from women who received either tailored smoking cessation texts or no text support (N = 33) were analysed using thematic analysis. Three themes emerged: convenience, high expectations and perceived source. Texting was regarded as a highly convenient mode of support delivery leading to high levels of attention to messages, although high convenience sometimes resulted in the value of a text being short-lived. Many who did not receive texts had high expectations for text support to intervene with routine smoking behaviour in real time. Those who received texts (with no real-time intervention element), however, felt they were helpful and supportive. Participants discussed how factors relating to perceived source, including personalization, personal relevance and salience of text automatization, could affect message attention and impact. Our findings provide insight into how maximizing personalization and personal relevance can increase the value of text message support and reduce the risk of disengagement.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Mães/psicologia , Abandono do Hábito de Fumar , Apoio Social , Envio de Mensagens de Texto , Adolescente , Adulto , Inglaterra , Feminino , Grupos Focais , Humanos , Gravidez , Pesquisa Qualitativa , Adulto Jovem
14.
Ultrastruct Pathol ; 37(6): 440-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23957452

RESUMO

DU145 human prostate carcinoma cells are typically poorly differentiated and contain only scantily distributed organelles. However, among numerous tumor cells randomly examined by electron microscopy out of in vitro cultivation, a peculiar, rare oncocyte-like cell type has been observed whose nucleus appears to be of small dimension and with a cytoplasm almost entirely filled with often distorted mitochondria. A few small, dispersed lysosomal bodies, small cisterns of the endoplasmic reticulum and a few glycogen patches can be found among highly osmiophilic contrasted, cytosolic spaces filled by innumerable ribonucleoproteins. The excessive population of mitochondria may have arisen from a more populated tumor cell type wherein the altered mitochondria are found to appear burgeoning into a spherical-like size progeny crowding the tumor cells. Literature cited between 1950 and the present suggests that this rare, oncocytic, benign prostatic tumor cell type is likely appear epigenetically, stemming from an original secretory cell, which is confirmed by the origin of the cell line originally maintained as cell line out of a brain metastatic, adenocarcinoma niche.


Assuntos
Adenocarcinoma/ultraestrutura , Neoplasias Encefálicas/ultraestrutura , Células Oxífilas/ultraestrutura , Neoplasias da Próstata/ultraestrutura , Adenocarcinoma/química , Adenocarcinoma/secundário , Neoplasias Encefálicas/química , Neoplasias Encefálicas/secundário , Linhagem Celular Tumoral , Forma do Núcleo Celular , Tamanho Celular , Glicogênio/análise , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Mitocôndrias/ultraestrutura , Células Oxífilas/química , Neoplasias da Próstata/química , Ribonucleoproteínas/análise
15.
Ultrastruct Pathol ; 36(5): 294-311, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23025648

RESUMO

Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align with others to facilitate formation of blood supply routes. Malignant cells would spread via ascites and through lymphatics.


Assuntos
Adenocarcinoma/ultraestrutura , Carcinoma/ultraestrutura , Neoplasias da Próstata/ultraestrutura , Adenocarcinoma/irrigação sanguínea , Animais , Apoptose , Basófilos/ultraestrutura , Carcinoma/irrigação sanguínea , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Entose , Humanos , Vasos Linfáticos/ultraestrutura , Lisossomos/ultraestrutura , Masculino , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Invasividade Neoplásica , Transplante de Neoplasias , Fenótipo , Neoplasias da Próstata/irrigação sanguínea , Células Estromais/ultraestrutura , Transplante Heterólogo
16.
BMJ Open ; 12(2): e053183, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35228280

RESUMO

OBJECTIVES: To explore patients' and healthcare practitioners' (HCPs) views about non-adherence to hypertension medication and potential content of a combined very brief face-to-face discussion (VBI) and digital intervention (DI). METHODS: A qualitative study (N=31): interviews with patients with hypertension (n=6) and HCPs (n=11) and four focus groups with patients with hypertension (n=14). Participants were recruited through general practices in Eastern England and London. Topic guides explored reasons for medication non-adherence and attitudes towards a potential intervention to support adherence. Stimuli to facilitate discussion included example SMS messages and smartphone app features, including mobile sensing. Analysis was informed methodologically by the constant comparative approach and theoretically by perceptions and practicalities approach. RESULTS: Participants' overarching explanations for non-adherence were non-intentional (forgetting) and intentional (concerns about side effects, reluctance to medicate). These underpinned their views on intervention components: messages that targeted forgetting medication or obtaining prescriptions were considered more useful than messages providing information on consequences of non-adherence. Tailoring the DI to the individuals' needs, regarding timing and number of messages, was considered important for user engagement. Patients wanted control over the DI and information about data use associated with any location sensing. While the DI was considered limited in its potential to address intentional non-adherence, HCPs saw the potential for a VBI in addressing this gap, if conducted in a non-judgemental manner. Incorporating a VBI into routine primary care was considered feasible, provided it complemented existing GP practice software and HCPs received sufficient training. CONCLUSIONS: A combined VBI-DI can potentially address intentional and non-intentional reasons for non-adherence to hypertension medication. For optimal engagement, recommendations from this work include a VBI conducted in a non-judgmental manner and focusing on non-intentional factors, followed by a DI that is easy-to-use, highly tailored and with provision of data privacy details about any sensing technology used.


Assuntos
Hipertensão , Aplicativos Móveis , Humanos , Hipertensão/tratamento farmacológico , Adesão à Medicação , Atenção Primária à Saúde , Pesquisa Qualitativa
17.
Ultrastruct Pathol ; 34(3): 140-60, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20455663

RESUMO

A human bladder carcinoma cell line RT4 was sham-treated with buffer or treated with ascorbate (VC) alone, menadione alone (VK(3)), or a combination of ascorbate:menadione (VC+VK(3)) for 1, 2, and 4 h. Cytotoxic damage was found to be treatment-dependent in this sequence: VC+VK(3)>VC>VK(3)>sham. The combined treatment induced the greatest oxidative stress, with early tumor cell injury affecting the cytoskeletal architecture and contributing to the self-excisions of pieces of cytoplasm freed from organelles. Additional damage, including a reduction in cell size, organelle alterations, nuclear damage, and nucleic acid degradation as well as compromised lysosome integrity, is caused by reactivation of DNases and the redox cycling of VC or VC+VK(3). In addition, cell death caused by VC+VK(3) treatment as well as by prolonged VC treatment is consistent with cell demise by autoschizis, not apoptosis. This report confirms and complements previous observations about this new mode of tumor cell death. It supports the contention that a combination of VC+VK(3), also named Apatone, could be co-administered as a nontoxic adjuvant with radiation and/or chemotherapies to kill bladder tumor cells and other cancer cells without any supplementary risk or side effects for patients.


Assuntos
Antineoplásicos/farmacologia , Ácido Ascórbico/farmacologia , Morte Celular/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vitamina K 3/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Quimioterapia Combinada , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Organelas/efeitos dos fármacos , Organelas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
18.
J Knee Surg ; 33(1): 12-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30544271

RESUMO

While femoral intramedullary alignment has been found to be the most accurate and reproducible method for proper femoral component orientation in total knee arthroplasty, certain situations preclude the use of intramedullary alignment, such as ipsilateral long-stem total hip arthroplasty, femoral shaft deformity (congenital or post-traumatic), capacious femoral canal, and retained hardware. These cases require alternative alignment guides, that is, extramedullary alignment. The purpose of this study was to determine the accuracy of intramedullary alignment in reproducing the femoral anatomic axis. Using 35 adult cadaveric femora without obvious clinical deformity, and 7 with proximal prosthetic devices blocking the passage of an intramedullary guide, the accuracy of the guide rod was assessed both anatomically and radiographically. In the seven femora with proximal femoral devices, the guide rod could not be completely seated, resulting in a greater degree of flexion of the guide rod compared with the mechanical axis of the femur, and a greater degree of varus compared with the anatomical axis, as compared with 35 femora without obvious deformity. In cases where seating of the intramedullary guide rod is either incomplete or impossible, extramedullary femoral guides allow more accurate determination of the distal femoral cut by referencing directly from the mechanical axis, that is, the center of the femoral head. We present case studies as examples of indications for use of an extramedullary femoral guide. In addition, we demonstrate two different techniques for extramedullary femoral alignment using fluoroscopic guidance in cases incompatible with intramedullary alignment.


Assuntos
Artroplastia do Joelho/métodos , Mau Alinhamento Ósseo/prevenção & controle , Pinos Ortopédicos , Fêmur/cirurgia , Adulto , Cadáver , Feminino , Fluoroscopia , Humanos , Prótese do Joelho , Masculino , Amplitude de Movimento Articular
19.
Int J Med Sci ; 5(2): 62-7, 2008 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-18392145

RESUMO

PURPOSE: To evaluate the safety and efficacy of oral Apatone (Vitamin C and Vitamin K3) administration in the treatment of prostate cancer in patients who failed standard therapy. MATERIALS AND METHODS: Seventeen patients with 2 successive rises in PSA after failure of standard local therapy were treated with (5,000 mg of VC and 50 mg of VK3 each day) for a period of 12 weeks. Prostate Specific Antigen (PSA) levels, PSA velocity (PSAV) and PSA doubling times (PSADT) were calculated before and during treatment at 6 week intervals. Following the initial 12 week trial, 15 of 17 patients opted to continue treatment for an additional period ranging from 6 to 24 months. PSA values were followed for these patients. RESULTS: At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p < or = 0.05). There were no dose-limiting adverse effects. Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment. CONCLUSION: Apatone showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.


Assuntos
Ácido Ascórbico/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Vitamina K 3/uso terapêutico , Administração Oral , Idoso , Ácido Ascórbico/administração & dosagem , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação , Vitamina K 3/administração & dosagem
20.
BMJ Open ; 8(3): e020133, 2018 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-29602848

RESUMO

OBJECTIVE: To determine the appropriateness of an online forum compared with face-to-face interviews as a source of data for qualitative research on adherence to secondary prevention medications after stroke. DESIGN: A comparison of attributes of two data sources, interviews and a forum, using realistic evaluation; a comparison of themes around adherence according to the Perceptions and Practicalities Approach (PAPA) framework. SETTING: Interviews were conducted in UK GP practices in 2013 and 2014; online posts were written by UK stroke survivors and family members taking part in the online forum of the Stroke Association between 2004 and 2011. PARTICIPANTS: 42 interview participants: 28 stroke survivors (age range 61-92 years) and 14 caregivers (85% spouses). 84 online forum participants: 49 stroke survivors (age range 32-72 years) and 33 caregivers (60% sons/daughters). RESULTS: 10 attributes were identified within the two data sources and categorised under three domains (context, mechanisms and outcomes). Participants' characteristics of forum users were often missing. Most forum participants had experienced a stroke within the previous 12 months, while interviewees had done so 1-5 years previously.All interview themes could be matched with corresponding themes from the forum. The forum yielded three additional themes: influence of bad press on taking statins, criticisms of clinicians' prescribing practices and caregiver burden in assisting with medications and being advocates for survivors with healthcare professionals. CONCLUSIONS: An online forum is an appropriate source of data for qualitative research on patients' and caregivers' issues with adherence to secondary prevention stroke medications and may offer additional insights compared with interviews, which can be attributed to differences in the approach to data collection.


Assuntos
Cuidadores , Internet , Pesquisa Qualitativa , Acidente Vascular Cerebral , Sobreviventes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral
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