RESUMO
The physical demands of professional female football have intensified in recent years. Supplements are only advised in addition to a healthy, balanced diet, but may warrant a greater prevalence in the professional game to support well-being, recovery and performance. Supplements used by players should be safe, legal and scientifically proven to be effective. An individual approach should be taken to using supplements dependant on the needs and goals of the player. Female players should aim to improve the frequency of protein intake throughout the day, whilst tailoring doses to individual body mass. Vitamin D supplementation is vital throughout the winter months in countries with limited sun exposure, however doses should be administered based on individual blood test results. Iron is likely to be important to the well-being of female athletes throughout the season, in particular during the menses. Omega-3 and collagen may be of greater benefit to female than male athletes during recovery from soft tissue injury, whilst probiotics and creatine are beneficial throughout the season for reducing risk of illness and optimising recovery, respectively. Ergogenic supplements for football include beta-alanine, nitrate and caffeine. Caution should be taken with caffeine use due to the varying tolerance of difference athletes and sleep impairments that can follow.
Assuntos
Futebol Americano , Futebol , Atletas , Cafeína , Suplementos Nutricionais , Feminino , Humanos , MasculinoRESUMO
PURPOSE: To review existing literature about fertility and sexuality of boys born with complex congenital genitourinary anomalies. METHODS: A Pubmed review was performed in December 2018 to identify the most relevant original manuscripts regarding male complex congenital conditions affecting the urogenital system in male patients including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and hypospadias. A comprehensive review was drafted exploring sexual dysfunction from a medical, psychosexual, surgical and reproductive point of view during transition from childhood (or adolescence) to adulthood. RESULTS: About 75% of men with SB have erectile dysfunction (ED) (Gamé et al. in Urology 67(3):566-570, 2006; Diamond et al. in 58(4):434-435, 1986). Most SB patients have impaired sexual development mainly due to diminished self-esteem, dependence on caregivers and lack of privacy (Blum et al. in Pediatrics 88(2):280-285, 1991). Men with BEEC have fewer intimate relationships than women because of the greater difficulties with issues regarding their genitalia and sexual activities (Deans et al. in Am J Obstet Gynecol 206(6):496.e1-496.e6, 2012). However, a good quality of life is achievable with the effective use of coping strategies (Deng et al. in Transl Androl Urol 7:941, 2018; Rikken et al. in BMC Womens Health 18(1):163, 2018; Friedler et al. in Reprod Biomed Online 32(1):54-61, 2016). Chordee occurs in 25% of all hypospadias patients. More severe hypospadias is related to a greater risk for complications. The long-term sexual quality of life (QoL) in men who underwent hypospadias surgery is influenced by a lot of factors. Therefore, an interactive and dynamic biopsychosocial model of sexual QoL was proposed. CONCLUSIONS: The care of patients with congenital urologic conditions becomes a challenge especially in the period of 'transition'. The goal of follow-up is a holistic management viewed from a medical, psychosexual, surgical end reproductive point. All patients should be asked for specific urinary, fecal or sexual concerns.
Assuntos
Infertilidade Masculina/etiologia , Disfunções Sexuais Fisiológicas/etiologia , Anormalidades Urogenitais/complicações , Extrofia Vesical/complicações , Epispadia/complicações , Humanos , Hipospadia/complicações , Masculino , Disrafismo Espinal/complicaçõesRESUMO
BACKGROUND: The psychosexual outcome in adolescents and young adults (AYA) men born with hypospadias is precarious. However, the factors responsible for impaired outcome in some AYA men have been understudied. AIM: To explore the outcome after hypospadias repair in childhood of AYA men aged 16-21 years and examine their opinion and their parents' opinion about this type of surgery. METHODS: Cross-sectional assessment of 193 AYA men born with hypospadias and 50 male controls was performed. Questionnaires such as the Decision Regret Scale, Pediatric Penile Perception Score, Sexual Quality of Life-Male, International Index of Erectile Function, and a custom-made questionnaire were used. The Decision Regret Scale and a custom-made questionnaire were also completed by the participants' parents. Physical examination including Hypospadias Objective Penile Evaluation and measuring stretched penile length was performed. OUTCOMES: This study reports the psychosexual functioning (ie, social, relational, and sexual), erectile and sexual function after childhood hypospadias repair, using ad hoc measures. In addition, the opinion about hypospadias repair of patients and their parents is represented. RESULTS: The number of surgeries and satisfaction regarding penile appearance were the most important factors associated with the opinion on hypospadias repair and the psychosexual outcome. Most AYA men were more satisfied with their penile appearance than the physician. 80% of men were satisfied with having had a childhood hypospadias repair, even though they had not been able to consent to surgery themselves. Erectile and ejaculation problems were mild and seen in approximately 10% of the population. CLINICAL IMPLICATIONS: Based on our data, deferring hypospadias repair until the patient can decide himself is not warranted. However, physicians who accept a suboptimal esthetic outcome and withdraw from repeated surgery may contribute importantly to the patient's well-being, especially in proximal forms of hypospadias. STRENGTHS & LIMITATIONS: This is one of the rare studies addressing the AYA's psychosexual outcome after childhood hypospadias repair. Strengths include the combination of clinical and psychosexual data from a very large cohort of men and their parents to provide a more holistic view. By entering this study, participants might have a different comfort level regarding their sexuality or have a different body image than the overall population of young men. CONCLUSION: Uncomplicated hypospadias surgery results in equal psychosexual outcome as controls and in high satisfaction rates; multiple surgeries are a risk factor for poorer outcomes. 80% of men are satisfied with childhood hypospadias repair. Tack LJW, Springer A, Riedl S, et al. Psychosexual Outcome, Sexual Function, and Long-Term Satisfaction of Adolescent and Young Adult Men After Childhood Hypospadias Repair. J Sex Med 2020;17:1665-1675.
Assuntos
Hipospadia , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Hipospadia/cirurgia , Masculino , Satisfação do Paciente , Satisfação Pessoal , Qualidade de Vida , Comportamento Sexual , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen-ultraviolet A (PUVA) with narrowband ultraviolet B (NB-UVB) have been small, nonrandomized and retrospective. OBJECTIVES: To conduct an observer-blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB-UVB for the treatment of chronic hand eczema unresponsive to topical steroids. METHODS: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB-UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). RESULTS: In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention-to-treat (ITT) response rate 43%]. In the NB-UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB-UVB 9) and at 12 weeks (PUVA 3, NB-UVB 4). Changes in DLQI were similar, with improvements in both groups. CONCLUSIONS: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems - PGA, mTLSS and DLQI - as measures of treatment response, the trial demonstrated that both PUVA and NB-UVB reduced the severity of chronic palmar hand eczema.
Assuntos
Eczema/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Terapia PUVA/métodos , Adulto , Idoso , Esquema de Medicação , Feminino , Ficusina/administração & dosagem , Ficusina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia PUVA/efeitos adversos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Método Simples-Cego , Raios Ultravioleta , Adulto JovemRESUMO
This study investigates the application of a hybrid system combining hollow-fibre membrane technology with the reductive abilities of magnetic nanoparticles for the remediation of toxic Cr(VI) and the azo dye, Remazol Black B. Nano-scale biogenic magnetite (Fe3O4), formed by microbial reduction of the mineral ferrihydrite, has a high reductive capacity due to the presence of Fe(II) in the mineral structure. The magnetic nanoparticles (approximately 20 nm) can be arrayed with Pd0 nanoparticles (approximately 5 nm) making a catalytically active nanomaterial. Membrane units, with and without nanoparticles, were challenged with either Cr(VI) or azo dye and some were supplemented with sodium formate, as an electron donor for contaminant reduction promoted by the Pd. The combination of Pd-magnetite with formate resulted in the most effective remediation strategy for both contaminants and the lifetime of the membrane unit was also increased, with 55% (19 days) and 70% (23 days) removal of the azo dye and Cr(VI), respectively. Low flow rates of 0.1 ml/min resulted in improved efficiencies due to increased contact time with the membrane/nanoparticle unit, with 70-75% removal of each contaminant. Chemical analyses of the nanoparticles post-exposure to Cr(VI) in the membrane modules indicated Pd to be more oxidized when Cr removal was maximized, and that the Cr was partially reduced to Cr(III) at the surface of the magnetite. These results have demonstrated that hollow-fibre membrane units can be enhanced for the removal of soluble, redox sensitive contaminants by incorporation of a layer of palladized biogenic nanoparticulate magnetite.
Assuntos
Compostos Azo/química , Cromo/química , Corantes/química , Paládio/química , Catálise , Microanálise por Sonda Eletrônica , Elétrons , Compostos Férricos/química , Óxido Ferroso-Férrico/química , Compostos Ferrosos/química , Formiatos/química , Geobacter/metabolismo , Nanopartículas/química , Nanoestruturas/química , Naftalenossulfonatos/química , Oxirredução , Oxigênio/química , Fatores de TempoRESUMO
The natural attenuation of hydrocarbons can be hindered by their rapid dispersion in the environment and limited contact with bacteria capable of oxidizing hydrocarbons. A functionalized composite material is described herein, that combines in situ immobilized alkane-degrading bacteria with an adsorbent material that collects hydrocarbon substrates, and facilitates biodegradation by the immobilized bacterial population. Acinetobacter venetianus 2AW was isolated for its ability to utilize hydrophobic n-alkanes (C10-C18) as the sole carbon and energy source. Growth of strain 2AW also resulted in the production of a biosurfactant that aided in the dispersion of complex mixtures of hydrophobic compounds. Effective immobilization of strain 2AW to the surface of Ottimat™ adsorbent hair mats via vapor phase deposition of silica provided a stable and reproducible biocatalyst population that facilitates in situ biodegradation of n-alkanes. Silica-immobilized strain 2AW demonstrated ca. 85% removal of 1% (v/v) tetradecane and hexadecane within 24 h, under continuous flow conditions. The methodology for immobilizing whole bacterial cells at the surface of an adsorbent, for in situ degradation of hydrocarbons, has practical application in the bioremediation of oil in water emulsions. Published 2011 American Institute of Chemical Engineers Biotechnol Prog., 2011.
Assuntos
Acinetobacter/metabolismo , Alcanos/metabolismo , Recuperação e Remediação Ambiental/métodos , Cabelo/microbiologia , Acinetobacter/química , Acinetobacter/genética , Acinetobacter/isolamento & purificação , Adsorção , Alcanos/química , Biodegradação Ambiental , Células Imobilizadas/química , Células Imobilizadas/metabolismo , Cabelo/química , Humanos , Estrutura Molecular , Petróleo/metabolismo , Esgotos/microbiologiaRESUMO
UNLABELLED: Humanized A33 (huA33) is a promising monoclonal antibody that recognizes A33 antigen, which is present in more than 95% of colorectal cancers and in normal bowel. In this study, we took advantage of quantitative PET to evaluate (124)I huA33 targeting, biodistribution, and safety in patients with colorectal cancer. We also determined the biodistribution of (124)I-huA33 when a large dose of human intravenous IgG (IVIG) was administered to manipulate the Fc receptor or when (124)I-huA33 was given via hepatic arterial infusion (HAI). METHODS: We studied 25 patients with primary or metastatic colorectal cancer; 19 patients had surgical exploration or resection. Patients received a median of 343 MBq (44.4-396 MBq) and 10 mg of (124)I-huA33. Nineteen patients received the antibody intravenously and 6 patients via HAI, and 5 patients also received IVIG. RESULTS: Ten of 12 primary tumors were visualized in 11 patients. The median concentration in primary colon tumors was 0.016% injected dose per gram, compared with 0.004% in normal colon. The PET-based median ratio of hepatic tumor uptake to normal-liver uptake was 3.9 (range, 1.8-22.2). Quantitation using PET, compared with well counting of serum and tissue, showed little difference. Prominent uptake in bowel hindered tumor identification in some patients. Pharmacokinetics showed that patients receiving IVIG had a significantly shorter serum half-time (41.6 ± 14.0 h) than those without (65.2 ± 9.8 h). There were no differences in clearance rates among the intravenous group, IVIG group, and HAI group, nor was there any difference in serum area under the curve, maximum serum concentration, or volume of distribution. Weak titers of human-antihuman antibodies were observed in 6 of 25 patients. No acute side effects or significant toxicities were associated with huA33. CONCLUSION: Good localization of (124)I-huA33 in colorectal cancer with no significant toxicity has been observed. PET-derived (124)I concentrations agreed well with those obtained by well counting of surgically resected tissue and blood, confirming the quantitative accuracy of (124)I-huA33 PET. The HAI route had no advantage over the intravenous route. No clinically significant changes in blood clearance were induced by IVIG.
Assuntos
Neoplasias Colorretais/imunologia , Radioisótopos do Iodo/farmacologia , Glicoproteínas de Membrana/química , Tomografia por Emissão de Pósitrons/métodos , Idoso , Área Sob a Curva , Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/metabolismo , Imunoglobulinas Intravenosas/farmacocinética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Radioimunoterapia/métodos , Resultado do TratamentoRESUMO
Mercuric chloride solutions have historically been used as pesticides to prevent bacterial, fungal and insect degradation of herbarium specimens. The University of Manchester museum herbarium contains over a million specimens from numerous collections, many preserved using HgCl(2) and its transformation to Hg(v)(0) represents a health risk to herbarium staff. Elevated mercury concentrations in work areas (â¼ 1.7 µg m(-3)) are below advised safe levels (<25 µg m(-3)) but up to 90 µg m(-3) mercury vapour was measured in specimen boxes, representing a risk when accessing the samples. Mercury vapour release correlated strongly with temperature. Mercury salts were observed on botanical specimens at concentrations up to 2.85 wt% (bulk); XPS, SEM-EDS and XANES suggest the presence of residual HgCl(2) as well as cubic HgS and HgO. Bacterially derived, amorphous nanospheres of elemental selenium effectively sequestered the mercury vapour in the specimen boxes (up to 19 wt%), and analysis demonstrated that the Hg(v)(0) was oxidised by the selenium to form stable HgSe on the surface of the nanospheres. Biogenic Se(0) can be used to reduce Hg(v)(0) in long term, slow release environments.
Assuntos
Mercúrio/química , Museus , Nanosferas/química , Selênio/química , Absorção , Monitoramento Ambiental/métodos , Eucalyptus/metabolismo , Geobacter/metabolismo , Mercúrio/toxicidade , Nanopartículas Metálicas/química , Nanopartículas/química , Folhas de Planta/metabolismo , Risco , Sulfetos/química , Temperatura , Difração de Raios XRESUMO
OBJECTIVE: To investigate the effect of three different tyrosine kinase inhibitors (TKIs) on the biodistribution of chimeric monoclonal antibody (mAb) cG250, which identifies carbonic anhydrase IX (CAIX), in nude mice bearing human renal cell carcinoma (RCC) xenografts. TKIs represent the best, but still suboptimal treatment for metastatic RCC (mRCC) and combined therapy or sequential therapy might be beneficial. CAIX is abundantly over expressed in RCC and clinical trials have shown abundant and specific tumour accumulation of cG250. Combining a TKI with mAb cG250, involved in a different effector mechanism, might lead to improved tumour responses and survival in patients with mRCC. MATERIALS AND METHODS: Nude mice bearing human RCC xenografts were treated orally with 0.75 mg/day sunitinib, 1 mg/day vandetanib, 1 mg/day sorafenib or vehicle control for 7 or 14 days. At 7 days, mice were injected i.v. with 185 kBq/5 µg (125) I-cG250. Mice were killed at predetermined days and cG250 biodistribution was determined. Tumours were analysed by immunohistochemistry for the presence of endothelial cells, laminin, smooth muscle actin, CAIX expression and uptake of mAb cG250. RESULTS: While on TKI treatment, tumour uptake of cG250 decreased dramatically, tumour growth was slightly inhibited and vascular density decreased considerably as judged by various markers. When treatment was stopped at 7 days, there was robust neovascularization, mainly at the tumour periphery. Consequently, cG250 uptake also recovered, albeit cG250 uptake appeared to be restricted to the tumour periphery where vigorous neovascularization was visible. CONCLUSIONS: Simultaneous administration of a TKI and mAb cG250 severely compromised mAb accumulation. However, shortly after discontinuation of TKI treatment mAb accumulation was restored. Combined treatment strategies with TKI and mAb should be carefully designed.
Assuntos
Anticorpos Monoclonais/metabolismo , Antineoplásicos/uso terapêutico , Anidrases Carbônicas/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Animais , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/patologia , Sinergismo Farmacológico , Feminino , Humanos , Imuno-Histoquímica , Indóis/uso terapêutico , Neoplasias Renais/patologia , Camundongos , Transplante de Neoplasias , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piperidinas/uso terapêutico , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Quinazolinas/uso terapêutico , Sorafenibe , SunitinibeRESUMO
High levels of naturally occurring arsenic are found in the shallow reducing aquifers of West Bengal, Bangladesh, and other areas of Southeast Asia. These aquifers are used extensively for drinking water and irrigation by the local population. Mechanisms for its release are unclear, although increasing evidence points to a microbial control. The type of organic matter present is of vital importance because it has a direct impact on the rate of microbial activity and on the amount of arsenic released into the ground water. The discovery of naturally occurring hydrocarbons in an arsenic-rich aquifer from West Bengal provides a source of potential electron donors for this process. Using microcosm-based techniques, seven sediments from a site containing naturally occurring hydrocarbons in West Bengal were incubated with synthetic ground water for 28 d under anaerobic conditions without the addition of an external electron donor. Arsenic release and Fe(III) reduction appeared to be microbially mediated, with variable rates of arsenic mobilization in comparison to Fe(III) reduction, suggesting that multiple processes are involved. All sediments showed a preferential loss of petroleum-sourced n-alkanes over terrestrially sourced sedimentary hydrocarbons n-alkanes during the incubation, implying that the use of petroleum-sourced n-alkanes could support, directly or indirectly, microbial Fe(III) reduction. Samples undergoing maximal release of As(III) contained a significant population of Sulfurospirillum sp., a known As(V)-reducing bacterium, providing the first evidence that such organisms may mediate arsenic release from West Bengali aquifers.
Assuntos
Arsenitos/metabolismo , Sedimentos Geológicos/química , Ferro/metabolismo , Petróleo/metabolismo , Microbiologia da Água , Poluentes Químicos da Água/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bangladesh , OxirreduçãoRESUMO
Photosynthesis rates and photosynthesis-leaf nutrient relationships were analysed in nine tropical grass and sedge species growing in three different ecosystems: a rain-fed grassland, a seasonal floodplain, and a permanent swamp, located along a hydrological gradient in the Okavango Delta, Botswana. These investigations were conducted during the rainy season, at a time of the year when differences in growth conditions between the sites were relatively uniform. At the permanent swamp, the largest variations were found for area-based leaf nitrogen contents, from 20 mmol m(-2) to 140 mmol m(-2), nitrogen use efficiencies (NUE), from 0.2 mmol (C) mol(-1) (N) s(-1) to 2.0 mmol (C) mol(-1) (N) s(-1), and specific leaf areas (SLA), from 50 cm(2) g(-1) to 400 cm(2) g(-1). For the vegetation growing at the rain-fed grassland, the highest leaf gas exchange rates, high leaf nutrient levels, a low ratio of intercellular to ambient CO(2) concentration, and high carboxylation efficiency were found. Taken together, these observations indicate a very efficient growth strategy that is required for survival and reproduction during the relatively brief period of water availability. The overall lowest values of light-saturated photosynthesis (A(sat)) were observed at the seasonal floodplain; around 25 micromol m(-2) s(-1) and 30 micromol m(-2) s(-1). To place these observations into the broader context of functional leaf trait analysis, relationships of photosynthesis rates, specific leaf area, and foliar nutrient levels were plotted, in the same way as was done for previously published 'scaling relationships' that are based largely on C(3) plants, noting the differences in the analyses between this study and the previous study. The within- and across-species variation in both A(sat) and SLA appeared better predicted by foliar phosphorus content (dry mass or area basis) rather than by foliar nitrogen concentrations, possibly because the availability of phosphorus is even more critical than the availability of nitrogen in the studied relatively oligotrophic ecosystems.
Assuntos
Fotossíntese , Poaceae/metabolismo , Botsuana , Dióxido de Carbono/metabolismo , Ecossistema , Nitrogênio/metabolismo , Fósforo/metabolismo , Áreas AlagadasRESUMO
The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.
Assuntos
Antioxidantes/farmacologia , Cognição/efeitos dos fármacos , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Hormônio do Crescimento Humano/efeitos dos fármacos , Hormônio do Crescimento Humano/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Análise por Pareamento , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Extratos VegetaisRESUMO
INTRODUCTION: The in vitro and in vivo behavior of the radiolabeled monoclonal antibody MORAb-003 was investigated as a prelude to a clinical trial. METHODS: The cellular retention of 111In- and 131I-labeled MORAb-003 was investigated using IGROV1 and SW620 cells. Biodistribution studies in tumor-bearing mice were performed with the more favorable agent. RESULTS: Five 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA) molecules were conjugated to MORAb-003 with no apparent loss of immunoreactivity. Radiolabeled MORAb-003 had a high affinity for the folate receptor alpha (FRA) expressed by both IGROV1 and SW620 cells and was found to bind to around 8 x 10(5) and 7 x 10(5) sites/cell, respectively. Both cancer cell lines were found to internalize both 131I- and 111In-labeled MORAb-003, but 111In was retained and 131I was released as iodide. In athymic mice, 111In-DOTA-MORAb-003 was cleared from the blood with a single exponential biological clearance rate of 110 h. The uptake in SW620 tumors was 32+/-5%ID/g after 4 days. The clearance rate of activity from normal organs such as liver, kidney and spleen was similar to the blood clearance and was 5.36%ID/g, 4.03%ID/g and 4.36%ID/g at 1 day postinjection and 2.14%ID/g, 1.65%ID/g and 3.74%ID/g after 8 days, respectively. In a pilot clinical study, the biodistribution and tumor targeting of 111In-MORAb-003 was assessed in three patients undergoing treatment with cold MORAb-003. CONCLUSION: MORAb-003 is an attractive antibody for radioimmunoscintigraphy and possibly radioimmunotherapy of FRA-expressing cancers in addition to its potential direct therapeutic effects.
Assuntos
Anticorpos Monoclonais/farmacocinética , Proteínas de Transporte/análise , Compostos Heterocíclicos com 1 Anel/farmacocinética , Radioimunodetecção/métodos , Receptores de Superfície Celular/análise , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Transporte Biológico Ativo , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Feminino , Receptores de Folato com Âncoras de GPI , Humanos , Imunoconjugados/farmacocinética , Radioisótopos de Índio/farmacocinética , Radioisótopos do Iodo/farmacocinética , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Nus , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Projetos Piloto , Radiografia , Compostos Radiofarmacêuticos/farmacocinética , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Distribuição TecidualRESUMO
The highly restricted distribution of human folate receptor-alpha (FRalpha) in normal tissues and its high expression in some tumors, along with its putative role in tumor cell transformation, make this antigen a suitable target for antigen-specific, monoclonal antibody-based immunotherapy for oncology indications. We have developed a therapeutic humanized monoclonal antibody with high affinity for FRalpha, named MORAb-003, which was derived from the optimization of the LK26 antibody using a whole cell genetic evolution platform. Here we show that MORAb-003 possesses novel, growth-inhibitory functions on cells overexpressing FRalpha. In addition, MORAb-003 elicited robust antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in vitro, and inhibited growth of human ovarian tumor xenografts in nude mice. Because of its multimodal activity in vitro and its safe toxicology profile in non-human primates, MORAb-003 development has recently been advanced to clinical trials involving ovarian cancer patients.
Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/imunologia , Imunoterapia/métodos , Neoplasias Ovarianas/tratamento farmacológico , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/imunologia , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Células CHO , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cricetinae , Cricetulus , Avaliação Pré-Clínica de Medicamentos , Feminino , Receptores de Folato com Âncoras de GPI , Humanos , Cinética , Camundongos , Camundongos Nus , Proteínas de Neoplasias/imunologia , Primatas/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: To investigate the views of osteopathic medical students on their preferred learning methods, their current use of computers as an educational tool, and their attitudes regarding the role of computers in medical education, based on their skill level. METHODS: A 27-item questionnaire was distributed to first-through fourth-year osteopathic medical students. Items asked students to assess their levels of computer skills and experience, their current use of computers as an educational tool, and their attitudes regarding the role of computers in medical education. RESULTS: Of the 246 students (80% of enrolled students) who responded to the questionnaire, a majority (129 [53%]) rated themselves as having intermediate computer skills, and the remaining students rated their skills as basic (69 [28%]) or advanced (46 [19%]). Most students (176 [72%]) felt that they learned best by both hearing and seeing or reading new material, that they learned more easily from a printed page than a computer screen, and that live lectures provided them with the best opportunity for learning. However, when compared with students who have basic and intermediate computer skills, students with advanced computer skills were more in favor of computer-assisted instruction and testing as well as a school requirement to own a computer and to use a laptop computer in class. CONCLUSIONS: Students' opinions of the importance of computer technology in medical education seem to be based mainly on their self-assessed technical competency levels. Understanding this dynamic may aid medical educators in the implementation of computer-assisted instruction.
Assuntos
Atitude Frente aos Computadores , Instrução por Computador , Medicina Osteopática/educação , Estudantes de Medicina , Adulto , Humanos , New Jersey , Inquéritos e QuestionáriosRESUMO
In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy-based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region-grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m(2)). Patients with locally advanced (UICC-TNM [International Union Against Cancer-tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of (131)I-huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose-limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of (131)I-huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting.
Assuntos
Anticorpos Monoclonais/farmacocinética , Glicoproteínas de Membrana/imunologia , Radioimunodetecção , Radioimunoterapia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Idoso , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismo , Distribuição Tecidual , Resultado do TratamentoRESUMO
The thermophilic, gram-positive bacterium Thermoterrabacterium ferrireducens coupled organotrophic growth to the reduction of sparingly soluble U(VI) phosphate. X-ray powder diffraction and X-ray absorption spectroscopy analysis identified the electron acceptor in a defined medium as U(VI) phosphate [uramphite; (NH4)(UO2)(PO4) . 3H2O], while the U(IV)-containing precipitate formed during bacterial growth was identified as ningyoite [CaU(PO4)2 . H2O]. This is the first report of microbial reduction of a largely insoluble U(VI) compound.
Assuntos
Peptococcaceae/crescimento & desenvolvimento , Fosfatos/metabolismo , Urânio/metabolismo , Microscopia Eletrônica de Varredura , Oxirredução , Peptococcaceae/metabolismo , Peptococcaceae/ultraestrutura , Espectrometria por Raios X , Difração de Raios XRESUMO
Microsatellites, or simple sequence repeats (SSRs) are very useful molecular markers for a number of plant species. They are commonly used in cultivar identification, plant variety protection, as anchor markers in genetic mapping, and in marker-assisted breeding. Early development of SSRs was hampered by the high cost of library screening and clone sequencing. Currently, large public SSR datasets exist for many crop species, but the number of publicly available, mapped SSRs for potato is relatively low (approximately 100). We have utilized a database mining approach to identify SSR-containing sequences in The Institute For Genomic Research Potato Gene Index database (http://www.tigr.org), focusing on sequences with size polymorphisms present in this dataset. Ninety-four primer pairs flanking SSR sequences were synthesized and used to amplify potato DNA. This study rendered 61 useful SSRs that were located in pre-existing genetic maps, fingerprinted in a set of 30 cultivars from South America, North America, and Europe or a combination thereof. The high proportion of success (65%) of expressed sequence tag-derived SSRs obtained in this work validates the use of transcribed sequences as a source of markers. These markers will be useful for genetic mapping, taxonomic studies, marker-assisted selection, and cultivar identification.
Assuntos
DNA de Plantas/genética , Etiquetas de Sequências Expressas , Genes de Plantas , Repetições de Microssatélites , Solanum tuberosum/genética , Mapeamento Cromossômico , Bases de Dados Factuais , Ligação Genética , Marcadores Genéticos , Genoma de PlantaRESUMO
Summary These guidelines for use of narrowband (TL-01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.
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Dermatopatias/radioterapia , Terapia Ultravioleta/métodos , Terapia Combinada , Eczema/radioterapia , Humanos , Linfoma Cutâneo de Células T/radioterapia , Psoríase/radioterapia , Doses de Radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/radioterapia , Terapia Ultravioleta/efeitos adversos , Terapia Ultravioleta/instrumentação , Reino Unido , Vitiligo/radioterapiaRESUMO
Learning to identify tumor and tumor-associated antigens in patients with squamous cell carcinoma of the head and neck (HNSCC) may bring about better diagnostic and prognostic evaluations of the disease, innovative therapies based on immunological approaches, and a better understanding of the biology of tumorigenesis. Serological analysis of tumor antigens by recombinant cDNA expression cloning (SEREX) has been used to identify antigens in head and neck cancer to which patients have produced high-titered IgG antibodies. Four cDNA expression libraries have been screened with sera from 6 head and neck cancer patients. Thirty-seven individual gene products were identified. Thirty-one previously characterized proteins and 6 genes coding for molecules that are only partially characterized or novel were isolated. Tissue expression was evaluated by Northern blot analysis, RT-PCR, and in one case, quantitative real-time PCR (qPCR) using Taqman technology. Clone AU-HN-15 encoded a protein highly expressed in HNSCC tissues and cell lines. Tissue adjacent to the tumor had negligible expression. There was low or negligible expression in normal tissues, except for the brain and thymus. AU-HN-15 is identical to KIAA0530; it is an uncharacterized protein previously cloned from brain tissue and has a zinc finger domain. The cDNA encoding this protein has also been isolated in SEREX screens of testicular cancer, breast cancer, and colorectal cancer. Whether AU-HN-15 represents a tumor-antigen target suitable for prognostic or therapeutic purposes is still being analyzed.