RESUMO
PURPOSE: A first of its kind experimental verification of dose-averaged linear energy transfer (LETd) optimized treatment plans for proton therapy has been carried out using a silicon-on-insulator microdosimeter at the Massachusetts General Hospital (MGH), Boston, USA. METHODS AND MATERIALS: Three clinical treatment plans of a typical ependymoma structure set were designed using the standard clinical approach, the proposed protocol approach, and a one-field approach. The plans were then reoptimized to reduce the LETd-weighted dose in the brain stem. All six plans were delivered in a solid water phantom and the experimental yDâ¾ measured. RESULTS: After LETd optimization, a reduction in yDâ¾ was found within the brain stem by an average of 12%, 19%, and 4% for the clinical, protocol, and one-field plans, respectively, while maintaining adequate coverage of the tumor structure. The experimental LETd-weighted doses were in agreement with the treatment planning system calculations and Monte Carlo simulations and reinforced the improvement of the optimization. CONCLUSIONS: This work demonstrates the first experimental verification of the clinical implementation of LETd optimization for patient treatment with proton therapy.
Assuntos
Neoplasias Encefálicas , Ependimoma , Transferência Linear de Energia , Método de Monte Carlo , Imagens de Fantasmas , Terapia com Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Terapia com Prótons/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Ependimoma/radioterapia , Ependimoma/diagnóstico por imagem , Radiometria/métodos , Radiometria/instrumentação , Tronco Encefálico/diagnóstico por imagem , Silício , Órgãos em Risco/efeitos da radiaçãoRESUMO
BACKGROUND: Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease with clinical sequelae such as itching, dyspigmentation and scarring. OBJECTIVES: We applied a previously described modular analysis approach to assess the molecular heterogeneity of patients with CLE. METHODS: Whole-blood transcriptomes of RNA sequencing data from a racially and ethnically diverse group of patients with CLE (n = 62) were used to calculate gene co-expression module scores. An unsupervised cluster analysis and k-means clustering based on these module scores were then performed. We used Fisher's exact tests and Kruskal-Wallis tests to compare characteristics between patient clusters. RESULTS: Six unique clusters of patients with CLE were identified from the cluster analysis. We observed that seven inflammation modules were elevated in two clusters of patients with CLE. Additionally, these clusters were characterized by interferon, neutrophil and cell-death signatures, suggesting that interferon-related proteins, neutrophils and cell-death processes could be driving the inflammatory response in these subgroups. Three different clusters had a predominant T-cell signature, which were supported by lymphocyte counts. CONCLUSIONS: Our data support a diverse molecular profile in CLE that further adds to the clinical variations of this skin disease, and may affect disease course and treatment selection. Future studies with a larger and diverse cohort of patients with CLE are warranted to confirm these findings.
Assuntos
Lúpus Eritematoso Cutâneo , Cicatriz , Estudos de Coortes , Testes Genéticos , Humanos , Lúpus Eritematoso Cutâneo/genéticaRESUMO
Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.
Assuntos
Leucoencefalopatias/psicologia , Pais/psicologia , Estresse Psicológico/psicologia , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
Compact silicon on insulator (SOI) microdosimeters have been used to characterise the radiation field of many different hadron therapy beams. SOI devices are particularly attractive in hadron therapy fields due to their spatial resolution being well suited to the sharp dose gradients at the end of the primary beam's range. Due to the small size of SOI's sensitive volumes (SVs), which are usually â¼1-10 [Formula: see text]m thick, the fabrication of these devices can present challenges which are not as common for more conventional thickness silicon devices such as silicon spectroscopy detectors. Microdosimetry is the study of the energy deposition in micrometre sized volumes representing biological sites and is a powerful approach to estimate the biological effect of radiation on the micron-scale level, in a cell. However, cell sizes vary extensively translating in different energy deposition spectra. This work studies SV thicknesses between 1 and 100 [Formula: see text]m using Geant4 and examines the impact of SV dimensions on microdosimetric quantities. The quantities studied were the frequency mean lineal energy, [Formula: see text], and the dose mean lineal energy, [Formula: see text]. Additionally the relative biological effectiveness (RBE), estimated by the microdosimetric kinetic model (MKM), is also investigated. To study the impact of the SV thickness, SOI microdosimeters were irradiated with proton, [Formula: see text] and [Formula: see text] ion beams with ranges of â¼160 mm, with the microdosimeter being set at various positions along the Bragg curve. It was found that [Formula: see text] was influenced the least in proton beams and increased for heavier ion beams. Conversely, [Formula: see text] was impacted by the SV thickness the most in proton beams and [Formula: see text] was the least. Similar to [Formula: see text], protons were impacted the most by the SV thickness when estimating the RBE using the MKM. The cause of these differences was largely due to the different densities of the delta electron track structure for the case of [Formula: see text] and the energy transferred to the medium from the primary beam for [Formula: see text].
Assuntos
Imagens de Fantasmas , Radiometria/instrumentação , Silício/química , Humanos , Cinética , Método de Monte Carlo , Prótons , Radiometria/métodos , Eficiência Biológica RelativaRESUMO
Microdosimetry is a particularly powerful method to estimate the relative biological effectiveness (RBE) of any mixed radiation field. This is particularly convenient for therapeutic heavy ion therapy (HIT) beams, referring to ions larger than protons, where the RBE of the beam can vary significantly along the Bragg curve. Additionally, due to the sharp dose gradients at the end of the Bragg peak (BP), or spread out BP, to make accurate measurements and estimations of the biological properties of a beam a high spatial resolution is required, less than a millimetre. This requirement makes silicon microdosimetry particularly attractive due to the thicknesses of the sensitive volumes commonly being â¼10 [Formula: see text]m or less. Monte Carlo (MC) codes are widely used to study the complex mixed HIT radiation field as well as to model the response of novel microdosimeter detectors when irradiated with HIT beams. Therefore it is essential to validate MC codes against experimental measurements. This work compares measurements performed with a silicon microdosimeter in mono-energetic [Formula: see text], [Formula: see text] and [Formula: see text] ion beams of therapeutic energies, against simulation results calculated with the Geant4 toolkit. Experimental and simulation results were compared in terms of microdosimetric spectra (dose lineal energy, [Formula: see text]), the dose mean lineal energy, yâ D and the RBE10, as estimated by the microdosimetric kinetic model (MKM). Overall Geant4 showed reasonable agreement with experimental measurements. Before the distal edge of the BP, simulation and experiment agreed within â¼10% for yâ D and â¼2% for RBE10. Downstream of the BP less agreement was observed between simulation and experiment, particularly for the [Formula: see text] and [Formula: see text] beams. Simulation results downstream of the BP had lower values of yâ D and RBE10 compared to the experiment due to a higher contribution from lighter fragments compared to heavier fragments.
Assuntos
Radioterapia com Íons Pesados , Método de Monte Carlo , Radiometria/métodos , Silício , Cinética , Modelos Biológicos , Eficiência Biológica RelativaRESUMO
Silicon-on-insulator (SOI) microdosimeters offer a promising method for routine quality assurance (QA) for hadron therapy due to their ease of operation and high spatial resolution. However, one complication which has been shown previously is that the traditional use of the mean chord length, [Formula: see text], calculated using Cauchy's formula, for SOI devices in clinical carbon ion fields is not appropriate due to the strong directionality of the radiation field. In a previous study, we demonstrated that the mean path length, [Formula: see text], which is the mean path of charged particles in the sensitive volume (SV), is a more appropriate method to obtain microdosimetric quantities and biological relevant values, namely the relative biological effectiveness (RBE) by means of the microdosimetric kinetic model. The previous work, which was limited to mono-energetic [Formula: see text] ion beams typical of heavy ion therapy (HIT), is extended here to investigate the [Formula: see text] in a pristine proton beam as well as for spread out Bragg peaks (SOBP) for both proton and carbon ion clinical beams. In addition, the angular dependence of the SOI device for a number of different SV designs is also investigated to quantify the effects which the alignment has on the [Formula: see text]. It is demonstrated that the [Formula: see text] can be accurately estimated along the depth of a pristine or SOBP using the energy deposition spectra for both proton and [Formula: see text] ion beams. This observation allows a quick and accurate estimation of the [Formula: see text] for experimental use.
Assuntos
Radioterapia com Íons Pesados/instrumentação , Radiometria/instrumentação , Silício , Desenho de Equipamento , Humanos , Cinética , Controle de Qualidade , Eficiência Biológica RelativaRESUMO
This paper presents the feasibility study of a novel 3D mesa bridge microdosimeter and its use for BNCT dosimetry. The performance of the microdosimeter was studied using Monte Carlo simulation. The clinical BNCT field at Kyoto University Reactor (KUR) using both thermal and epithermal irradiation modes were used in this study. Results show that this microdosimeter can be utilised as an effective tool to measure microdosimetric spectrum in the BNCT field and experimental validation will follow once KUR is operational.
Assuntos
Terapia por Captura de Nêutron de Boro , Radiometria/instrumentação , Partículas alfa/uso terapêutico , Simulação por Computador , Estudos de Viabilidade , Humanos , Lítio/análise , Método de Monte Carlo , Neoplasias/radioterapia , Imagens de Fantasmas , Radiometria/estatística & dados numéricos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricos , SilícioRESUMO
Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy in young patients, and different mutations in the genes encoding its subunits are still being uncovered. We report 2 patients with cystic leukoencephalopathy and complex I deficiency with recessive mutations in NDUFA2, an accessory subunit of complex I. The first patient was initially diagnosed with a primary systemic carnitine deficiency associated with a homozygous variant in SLC22A5, but also exhibited developmental regression and cystic leukoencephalopathy, and an additional diagnosis of complex I deficiency was suspected. Biochemical analysis confirmed a complex I deficiency, and whole-exome sequencing revealed a homozygous mutation in NDUFA2 (c.134A>C, p.Lys45Thr). Review of a biorepository of patients with unsolved genetic leukoencephalopathies who underwent whole-exome or genome sequencing allowed us to identify a second patient with compound heterozygous mutations in NDUFA2 (c.134A>C, p.Lys45Thr; c.225del, p.Asn76Metfs*4). Only 1 other patient with mutations in NDUFA2 and a different phenotype (Leigh syndrome) has previously been reported. This is the first report of cystic leukoencephalopathy caused by mutations in NDUFA2.
Assuntos
Sequenciamento do Exoma , Leucoencefalopatias/genética , Mitocôndrias/genética , NADH Desidrogenase/genética , Criança , Pré-Escolar , Exoma/genética , Feminino , Humanos , Lactente , Doença de Leigh/genética , Doença de Leigh/fisiopatologia , Leucoencefalopatias/fisiopatologia , Masculino , Mitocôndrias/patologia , Mutação , Membro 5 da Família 22 de Carreadores de Soluto/genéticaRESUMO
Using the CMRP 'bridge' µ+ probe, microdosimetric measurements were undertaken out-of-field using a therapeutic scanning proton pencil beam and in-field using a 12C ion therapy field. These measurements were undertaken at Mayo Clinic, Rochester, USA and at HIMAC, Chiba, Japan, respectively. For a typical proton field used in the treatment of deep-seated tumors, we observed dose-equivalent values ranging from 0.62 to 0.99 mSv/Gy at locations downstream of the distal edge. Lateral measurements at depths close to the entrance and along the SOBP plateau were found to reach maximum values of 3.1 mSv/Gy and 5.3 mSv/Gy at 10 mm from the field edge, respectively, and decreased to ~0.04 mSv/Gy 120 mm from the field edge. The ability to measure the dose-equivalent with high spatial resolution is particularly relevant to healthy tissue dose calculations in hadron therapy treatments. We have also shown qualitatively and quantitively the effects critical organ motion would have in treatment using microdosimetric spectra. Large differences in spectra and RBE10 were observed for treatments where miscalculations of 12C ion range would result in critical structures being irradiated, showing the importance of motion management.
Assuntos
Radioterapia com Íons Pesados/métodos , Microtecnologia/instrumentação , Imagens de Fantasmas , Terapia com Prótons/métodos , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Silício/química , Simulação por Computador , Humanos , Radiometria/métodos , Dosagem RadioterapêuticaRESUMO
The temperature-dependent development of tomato psyllid (also called potato psyllid), Bactericera cockerelli (Sulc), was studied in the laboratory at seven constant temperatures (8, 10, 15, 20, 23, 27, and 31°C), 50-60% RH, and a photoperiod of 16:8 (L:D) h on leaves of whole potato (Solanum tuberosum L.) and tomato (Solanum lycopersicum L.) plants. Developmental time in days for immature stages and total development (egg to adult) on both host species were inversely proportional to temperature between 8 and 27°C but increased at 31°C. One linear and two nonlinear models were fitted to the data. The lower developmental thresholds, calculated using the linear model for egg, total nymph, and total development (from oviposition to adult emergence) were 7.9, 4.2, and 7.1°C (reared on potato) and 7.2, 5.3, and 7.5°C (reared on tomato), respectively. The thermal constant (K) for total development was 358 (reared on potato), and 368 (reared on tomato) degree-days (DD). Two nonlinear models, Briere and Lactin, fit the data well as measured by goodness-of-fit criteria, the residual sum of square (RSS) and Akaike information criterion (AIC). Temperature threshold parameters for these nonlinear models (T(0), T(opt), and T(max)) were estimated for eggs, total nymphal stages, and total development time (egg to adult). The Briere model is highly recommended for the description of temperature-dependent development of tomato psyllid. Results from this study will provide basic information on the biology of tomato psyllid and have potential for the development of predictive models of the seasonal progress of this invasive pest.
Assuntos
Hemípteros/crescimento & desenvolvimento , Interações Hospedeiro-Parasita , Solanum lycopersicum/parasitologia , Solanum tuberosum/parasitologia , Temperatura , Animais , Feminino , Modelos Lineares , Masculino , Ninfa/crescimento & desenvolvimento , Óvulo/crescimento & desenvolvimentoRESUMO
Two of the most potent vasoconstrictors, endothelin-1 (ET-1) and angiotensin II (Ang II), are upregulated in fructose hypertensive rats. It is unknown whether an interrelationship exists between these peptides that may contribute to the development of fructose-induced hypertension. The objective of this study was to investigate the existence of an interaction between the endothelin and renin angiotensin systems that may play a role in the development of fructose-induced hypertension. High fructose feeding and treatment with either bosentan, a dual endothelin receptor antagonist, or with L-158,809, an angiotensin type 1 receptor antagonist, were initiated simultaneously in male Wistar rats. Systolic blood pressure, fasted plasma parameters, insulin sensitivity, plasma Ang II, and vascular ET-1-immunoreactivity were determined following 6 weeks of high fructose feeding. Rats fed with a high fructose diet exhibited insulin resistance, hyperinsulinemia, hypertriglyceridemia, hypertension, and elevated plasma Ang II. Treatment with either bosentan or L-158,809 significantly attenuated the rise in blood pressure with no effect on insulin levels or insulin sensitivity in fructose-fed rats. Bosentan treatment significantly reduced plasma Ang II levels, while L-158,809 treatment significantly increased vascular ET-1-immunoreactivity in fructose-fed rats. Thus, treatment with the endothelin receptor antagonist prevented the development of fructose-induced hypertension and decreased plasma Ang II levels. These data suggest that ET-1 contributes to the development of fructose-induced hypertension through modulation of Ang II levels.
Assuntos
Angiotensina II/metabolismo , Carboidratos da Dieta/administração & dosagem , Endotelina-1/fisiologia , Frutose/administração & dosagem , Hipertensão/fisiopatologia , Angiotensina II/antagonistas & inibidores , Angiotensina II/sangue , Animais , Pressão Sanguínea , Teste de Tolerância a Glucose , Imidazóis/farmacologia , Imuno-Histoquímica , Resistência à Insulina , Masculino , Ratos , Ratos Wistar , Tetrazóis/farmacologiaRESUMO
The purpose of this study was to determine whether decreased day lengths affect reproduction or the immune system in inbred mice. Irrespective of a nocturnal pineal melatonin rise, the signal for day length information, body and testis weights were the same in various strains 8 weeks after transfer from long to short days (16 to 8 h of light/day) compared to mice that remained in long days. Serum testosterone was unaffected by the photoperiod shift. The second goal was to determine whether the shift from long to short days influenced lymphocyte populations in spleen or blood, as well as innate and cell-mediated immune cell functions in C3H/HeN mice, an inbred strain with a robust melatonin rhythm. By flow cytometry, a stable percentage and number of B cells, T cells, and natural killer cells were identified in spleen from mice in both long and short days during the day and night. This complement of immunophenotypes in spleen suggests that equivalent functional capabilities persist in secondary lymphoid tissue of mice irrespective of day length. This was supported by findings that cytolytic activity by splenic natural killer cells (innate immunity) and antigen-induced T cell-dependent B cell antibody production (adaptive immunity) were similar in mice in long and short days. In blood, cell numbers but not helper T cell subset percentages (i.e., naive, memory, cytotoxic, or activated) were augmented in mice in short compared to long days, a consequence of increased circulating B cells. Day length differences in certain immunophenotypes in circulation may forecast photoperiod-mediated alterations in responsiveness to pathogens that are associated with a change in season. At night, the reduced proportion of cytotoxic T cells (long and short days), as well as increases in the percentage of activated T cells (long days), B cells (short days), and NK cell activity (long and short days) relative to daytime, suggests that surveillance and function by select immunophenotypes may adapt to circadian transitions even in highly inbred species. Thus, inbred mice retain capabilities for photoperiod to influence trait-specific aspects of immune cell but not reproductive function.
Assuntos
Imunidade/genética , Imunidade/fisiologia , Camundongos Endogâmicos/fisiologia , Fotoperíodo , Reprodução/genética , Reprodução/fisiologia , Animais , Formação de Anticorpos/genética , Formação de Anticorpos/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Imunidade Celular/genética , Imunidade Celular/fisiologia , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Masculino , Melatonina/sangue , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Tamanho do Órgão/fisiologia , Especificidade da Espécie , Subpopulações de Linfócitos T/imunologia , Testículo/fisiologia , Testosterona/sangueRESUMO
Antimicrobial peptides are a source of novel agents that could be useful for treatment of the chronic lung infections that afflict cystic fibrosis (CF) patients. Efficacy depends on antimicrobial activity against the major pathogens of CF patients, Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae, in the environment of the CF patient's airway. We describe the in vitro efficacies of derivatives of histatins, which are histidine-rich peptides produced by the salivary glands of humans and higher primates. P-113, a peptide containing 12 of the 24 amino acid residues of the parent molecule, histatin 5, retained full antibacterial activity and had a good spectrum of activity in vitro against the prominent pathogens of CF patients. However, P-113 was not active in the presence of purulent sputum from CF patients. In contrast, P-113D, the mirror-image peptide with the amino acid residues in the D configuration, was stable in sputum, was as active as P-113 against pathogens of CF patients in the absence of sputum and retained significant activity in the presence of sputum from CF patients. Recombinant human DNase, which effectively liquefies sputum, enhanced the activity of P-113D in undiluted sputum against both exogenous (added) bacteria and endogenous bacteria. Because of its properties, P-113D shows potential as an inhalant in chronic suppressive therapy for CF patients.
Assuntos
Antibacterianos/farmacologia , Fibrose Cística/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Saralasina/farmacologia , Escarro/microbiologia , Fibrose Cística/complicações , Fibrose Cística/metabolismo , Desoxirribonucleases/farmacologia , Humanos , Isomerismo , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Saralasina/química , Escarro/química , EstereoisomerismoRESUMO
In Siberian hamsters (Phodopus sungorus), short days suppress reproductive function and lymphocyte proliferation. To determine whether melatonin influences cell-mediated immunity through a direct action on lymphocyte proliferation, in vitro responsiveness to mitogens and melatonin was assessed in systemic and splenic lymphocytes from adult female Siberian hamsters housed in either long or short days for 13 weeks. Short days provoked reproductive regression and reduced lymphocyte proliferation. Physiological concentrations of melatonin (50 pg/ml) inhibited in vitro proliferation of circulating lymphocytes, whereas higher concentrations (> or = 500 pg/ml) were required to inhibit proliferation of splenic lymphocytes. Immunomodulatory effects of melatonin were restricted to lymphocytes from long-day hamsters-in vitro melatonin had no effect on circulating or splenic lymphocytes from females in short days. Responsiveness to melatonin in short-day lymphocytes may be restrained by the already expanded nightly pattern of melatonin secretion in short days. These data support the hypothesis that melatonin acts directly on lymphocytes from long-day hamsters to suppress blastogenesis.
Assuntos
Linfócitos/citologia , Melatonina/fisiologia , Fotoperíodo , Animais , Divisão Celular/fisiologia , Cricetinae , Feminino , Técnicas In Vitro , Melatonina/farmacologia , Phodopus , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Baço/citologiaRESUMO
Through the analysis of a series of 25 peptides composed of various portions of the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of histatin 5, as the smallest fragment that retains anticandidal activity comparable to that of the parent compound. Amidation of the P-113 C terminus increased the anticandidal activity of P-113 approximately twofold. The three histidine residues could be exchanged for three hydrophobic residues, with the fragment retaining anticandidal activity. However, the change of two or more of the five basic (lysine and arginine) residues to uncharged residues resulted in a substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P-113D, was as active against Candida albicans as the L-amino-acid form. In vitro MIC tests in low-ionic-strength medium showed that P-113 has potent activity against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. These results identify P-113 as a potential antimicrobial agent in the treatment of oral candidiasis.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Proteínas e Peptídeos Salivares/farmacologia , Saralasina/farmacologia , Sequência de Aminoácidos , Resistência Microbiana a Medicamentos , Histatinas , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Fragmentos de Peptídeos/farmacologia , Saralasina/química , Homologia de Sequência de AminoácidosRESUMO
AIMS: To employ an in vitro screening regime to select a probiotic Bifidobacterium strain to complement resistant starch (Hi-maizetrade mark) in a synbiotic yoghurt. METHODS AND RESULTS: Of 40 Bifidobacterium isolates examined, only B. lactis Laftitrade mark B94 possessed all of the required characteristics. This isolate hydrolysed Hi-maizetrade mark, survived well in conditions simulating passage through the gastrointestinal tract and possessed technological properties suitable for yoghurt manufacture. It grew well at temperatures up to 45 degrees C, and grew to a high cell yield in an industrial growth medium. In addition to resistant starch, the organism was able to utilize a range of prebiotics including inulin, and fructo-, galacto-, soybean- and xylo-oligosaccharides. Pulse field gel electrophoresis of restriction enzyme cut chromosomal DNA revealed that B. lactis Laftitrade mark B94 was very closely related to the B. lactis Type Strain (DSM 10140), and to the commercial strains B. lactis Bb-12 and B. lactis DS 920. However, B. lactis Laftitrade mark B94 was the only one of these isolates that could hydrolyse Hi-maizetrade mark. This phenotypic difference did not appear to be due to the presence of plasmid encoded amylase. Bifidobacterium lactis Laftitrade mark B94 survived without substantial loss of viability in synbiotic yoghurt containing Hi-maizetrade mark during storage at 4 degrees C for six weeks. CONCLUSION: Bifidobacterium lactis Laftitrade mark B94 is a promising new yoghurt culture that warrants further investigation to assess its probiotic potential. SIGNIFICANCE AND IMPACT OF THE STUDY: In vitro screening procedures can be used to integrate complementary probiotic and prebiotic ingredients for new synbiotic functional food products.
Assuntos
Bifidobacterium/crescimento & desenvolvimento , Probióticos , Amido/metabolismo , Iogurte/microbiologia , Bifidobacterium/genética , Bifidobacterium/metabolismo , Bile/microbiologia , Meios de Cultura , Sistema Digestório/microbiologia , Humanos , Hidrólise , Oligossacarídeos/metabolismo , Plasmídeos , Temperatura , Zea mays/química , Zea mays/metabolismoRESUMO
Serious shrimp-disease outbreaks have reduced shrimp production and slowed industry growth since 1991. This paper tests factors such as farm sitting and design, and farm-management practices for relationships with disease occurrence. Logistic regression is used to analyze farm-level data from 3951 shrimp farms in 13 Asian countries. Disease occurrence is modeled as a 0-1 variable where 1 = disease loss of > or = 20% to any 1 crop, and 0 = losses of < 20%. Logistic regression is performed for each of 3 levels of shrimp culture intensity, i.e. extensive, semi-intensive, and intensive. Attempts to apply logistic regression models to each country were not successful due to insufficient data for most countries. Factors affecting disease occurrences were quite different for different farming intensities. Farms that had larger pond production areas, with larger number of farms discharging effluent into their water supply canals, and removed silt had greater disease occurrence. On the other hand, farms that practiced polyculture and took water from the sea through a canal had lower disease occurrence.
Assuntos
Decápodes , Pesqueiros/estatística & dados numéricos , Animais , Ásia/epidemiologia , Pesqueiros/métodos , Modelos Logísticos , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the single dose-response effects of grapefruit juice on terfenadine disposition and electrocardiographic measurements. METHODS: Twelve healthy males received 250 ml water or regular- or double-strength grapefruit juice with 60 mg terfenadine in a randomized crossover trial. Plasma concentrations of the cardiotoxic agent terfenadine and the active antihistaminic metabolite terfenadine carboxylate were determined over 8 hours. The QTc interval was monitored. RESULTS: Terfenadine concentrations were measurable (> 1 ng/ml) in 27 (20%; p < 0.001) and 39 (30%; p < 0.001) samples from individuals treated with regular- and double-strength grapefruit juice, respectively, compared to only four (3%) samples with water. Terfenadine plasma peak drug concentration (Cmax) was also higher. Terfenadine carboxylate area under the plasma drug concentration-time curve (AUC), Cmax, and time to reach Cmax (tmax) were increased by both strengths of juice. However, terfenadine carboxylate apparent elimination half-life (t1/2) was not altered. The magnitude of the interaction of terfenadine carboxylate AUC and Cmax ranged severalfold and correlated among individuals for regular-strength (r2 = 0.87; p < 0.0001) and double-strength (r2 = 0.78; p < 0.0001) grapefruit juice. No differences in the pharmacokinetics of terfenadine and terfenadine carboxylate were observed between the two strengths of grapefruit juice. QTc interval was not altered. CONCLUSIONS: A normal amount of regular-strength grapefruit juice produced maximum single-dose effects on terfenadine and carboxylic acid metabolite pharmacokinetics. The mechanism likely involved reduced presystemic drug elimination by inhibition of more than one metabolic pathway. The extent of the interaction was not sufficient to produce electrocardiographic changes. However, the pharmacokinetic effects were highly variable among individuals. This study further enhances the awareness of the potential for a serious interaction between grapefruit juice and terfenadine.
Assuntos
Antialérgicos/farmacocinética , Antiasmáticos/farmacocinética , Citrus/efeitos adversos , Interações Alimento-Droga , Terfenadina/farmacocinética , Adulto , Área Sob a Curva , Bebidas , Eletrocardiografia/efeitos dos fármacos , Humanos , Masculino , Oxirredução , Valores de ReferênciaRESUMO
Candida infections involve multiple risk factors. Among the independent risk factors identified, the degree of colonization of Candida spp. allows the prediction of subsequent severe candidosis in surgical patients. The aim of this study was to assess among 13 selected variables, those that would best predict the perioperative variation of the colonization index (CI) of Candida spp. in cardiovascular surgical patients. The colonization index took into account the number of sites colonized and the density of growth. The results showed that 56.8% of our patients were colonized perioperatively. A total of 116 isolates were identified and Candida albicans accounted for 76.7% of the strains. Among the patients who developed post-surgical Candida infections, 57.1% had an increase of the CI early after the operation. By univariate analysis, three factors were significantly associated with an increase of the CI in patients after surgery; sex (female), the duration of central intravascular catheterization and the length of stay in the surgical intensive care unit (SICU). Epidemiological data could help predict those patients who are at risk of developing Candida infections.