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1.
J Food Sci Technol ; 55(7): 2569-2578, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30042573

RESUMO

The aim of this paper was to study, step by step, the effect of ingredients and storage conditions on several properties of both the maize-based dough and the final product, during the new polenta-based snack food developing. Two different maize flours were characterized through water activity determination, particle size analysis, scanning electronic microscopy; then, dough made with different ratio of these were evaluated for mechanical properties and microstructure. According to the preliminary physicochemical characterization of both flour and dough, the final formulation was chosen for the polenta-based snacks. Thus, mechanical and sensory analyses, as well as microstructure determination, were performed on the final product. Results showed that the two maize flours presented different particle size distribution and gelatinization enthalpy, and affected the mechanical properties of intermediate products. The storage conditions dramatically affected the characteristics of the final products. Sensory results demonstrated that breading improves the crispness of external part but keeping creamy the product inside. The chosen approach was useful for understanding that flour particle size and storage are the critical factors that should be considered for this type of snack. The best formulation was made by mixing coarse and fine maize flours and by adding a batter.

2.
Radiologia ; 58(2): 129-35, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-26494491

RESUMO

OBJECTIVE: To analyze the usefulness of diffusion magnetic resonance (MR) sequences before and after prostatic artery embolization (PAE) in patients with benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: We analyzed MR studies done before (7-10 days) and after (30 days) PAE in 19 patients with BPH treated with PAE between June 2012 and December 2013. We used 1.5 Tesla scanners with body surface coils. In pre-PAE MR studies, we recorded mean b40 values and minimum (min) and maximum (max) apparent diffusion coefficient (ADC) values. In post-PAE MR studies, we recorded b40, b400, and b1000 values and min, mean, and max ADC values. We compared diffusion behavior/ADC before and after PAE and areas without ischemia. We correlated these with decreased prostatic volume (PV). RESULTS: We identified ischemia with contrast in 8 (42.1%) patients. No significant difference was found in mean b40 (p= 0.1650) or in the b40 ratio (p= 0.8868) between patients with ischemia and those without before PAE. Min b40, b40 ratio, and min ADC values differed significantly between ischemic areas and nonischemic areas within patients [p= 0.048 (b40min and ratio) and p= 0.002 (min ADC)]. No significant correlation was found between the percentage decrease in PV and mean b40 (p= 0.8490) or b40 ratio (p=0.8573). CONCLUSION: Post-PAE ischemia generates objective changes in diffusion and ADC values that enable ischemic sectors to be differentiated from nonischemic sectors. Future studies should analyze whether it is possible to subjectively differentiate between these areas through the visualization of nonischemic sectors and the feasibility of replacing them with contrast to detect ischemia.


Assuntos
Imagem de Difusão por Ressonância Magnética , Isquemia/diagnóstico por imagem , Hiperplasia Prostática/diagnóstico por imagem , Embolização Terapêutica , Humanos , Masculino
3.
Agric Food Econ ; 10(1): 29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36373082

RESUMO

Fish is an important source of healthy proteins and an important economic sector in Mediterranean countries. Despite the wealth of knowledge acquired in Western countries, a gap has been found in studies in developing countries, as in the Mediterranean southern shore. Therefore, we aimed to investigate consumers' perceptions of finfish attributes, with qualitative tools as focus groups, given the exploratory nature of the research. The focus groups have been held in Italy, Lebanon, Spain, and Tunisia; in each country, one was held in seaside areas and one in inland areas, in order to control for the availability of fish that shapes consumers' evaluations and expectations. The focus groups have been analysed through content and semantic analyses. Results of the study yielded main themes recurring in the discussions that have been categorized along such dimensions: (1) definition of fish products; (2) context; (3) search attributes; (4) experience attributes; and (5) credence attributes. Among attributes, the ones mostly guiding consumers' choices seem to be freshness and fish species, which are used as proxies for quality and sensory attributes. Most of the respondents preferred delicate white fish, while some exceptions were found in Tunisian respondents preferring blue fish and they also were the only ones who were not looking for convenient and already cleaned products. Trust also represented a critical element in guiding the decisions of consumers: with a lack of trust, consumers deviate from preferring local products, as noticeable especially in Lebanese respondents' opinions. Credence attributes such as animal welfare and sustainability received a minor attention from all the respondents.

4.
Food Sci Technol Int ; 17(3): 223-32, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21693619

RESUMO

The shelf life of fresh Italian pork sausages packed in modified atmosphere was studied. Samples were packed using different levels of oxygen (high and low) with different levels of carbon dioxide (high-low) in the atmospheres headspace and were stored at 4 °C for 9 days. Microbial, physiochemical and sensory parameters were analyzed during storage. A consumer test was performed to determine the critical acceptability levels. Sensory data were mathematically modelled to estimate product shelf life. A first-order kinetic model and a Weibull-type model aptly described, respectively, the changes in fresh pork sausage odor and color over storage time. These models may be used to predict the sensory shelf life of fresh pork sausage. Results showed that 20% O(2) and 70% CO(2) extend fresh pork sausage shelf life to 9 days at 4 °C. The microbial quality of the samples at the critical sensory level of acceptability was within the range of microbial acceptability.


Assuntos
Atmosfera , Microbiologia de Alimentos , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Produtos da Carne/microbiologia , Animais , Dióxido de Carbono/química , Comportamento do Consumidor , Humanos , Concentração de Íons de Hidrogênio , Cinética , Odorantes , Suínos , Fatores de Tempo
5.
Physiotherapy ; 106: 36-42, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32026844

RESUMO

OBJECTIVE: To compare a 6-week virtual reality (VR) rehabilitation programme with a conventional rehabilitation programme in patients with Parkinson's disease. DESIGN: Prospective, single-blinded, randomised controlled trial. SETTING: Outpatients. PARTICIPANTS: Fifty-one patients with Parkinson's disease were assigned at random to a VR rehabilitation programme or a conventional rehabilitation programme. INTERVENTIONS: Both programmes ran for 6 consecutive weeks, with a 40-minute session three times per week. MAIN OUTCOME MEASURES: The Balance Berg Scale (BBS) was used to measure balance. Secondary outcome measures were: Dynamic Gait Index (DGI) to evaluate ability to adapt gait to complex walking tasks; Disabilities of the Arm, Shoulder and Hand (DASH) scale to measure performance of the upper limb; and Short Form 36 (SF-36) to evaluate quality of life. RESULTS: The VR rehabilitation programme led to an increase in BBS score {45.6 [standard deviation (SD) 7.9] vs 49.2 (SD 8.1), mean difference 3.6, 95% confidence interval (CI) 1.3 to 5.9; P=0.003}, DGI score [18.7 (SD 4.7) vs 20.2 (SD 4.2), mean difference 1.6, 95% CI 0.6 to 2.5; P=0.003] and SF-36 mental composite score [37.7 (SD 11.4) vs 43.5 (SD 9.2), mean difference 5.8, 95% CI 0.4 to 11.3; P=0.037], and a decrease in DASH scale score [29.6 (SD 17.5) vs 21.6 (SD 15.1), mean difference -7.9, 95% CI -13.7 to -2.2; P=0.009]. In contrast, the conventional rehabilitation programme only led to a decrease in DASH scale score [30.3 (SD 18.1) vs 25.1 (SD 15.8), mean difference -5.2, 95% CI -8.8 to -1.5; P=0.007]. CONCLUSION: These findings suggest that rehabilitation is useful in Parkinson's disease, and the VR rehabilitation programme was more effective in determining overall improvement than the conventional rehabilitation programme. CLINICAL TRIAL REGISTRATION NUMBER: NCT02807740.


Assuntos
Doença de Parkinson/reabilitação , Modalidades de Fisioterapia , Realidade Virtual , Idoso , Avaliação da Deficiência , Feminino , Marcha , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Equilíbrio Postural , Estudos Prospectivos , Qualidade de Vida , Método Simples-Cego
6.
Sci Rep ; 10(1): 7981, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409745

RESUMO

In real paramagnets, there is always a subtle many-body contribution to the system's energy, which can be regarded as a small effective local magnetic field (Bloc). Usually, it is neglected, since it is very small when compared with thermal fluctuations and/or external magnetic fields (B). Nevertheless, as both the temperature (T) → 0 K and B → 0 T, such many-body contributions become ubiquitous. Here, employing the magnetic Grüneisen parameter (Γmag) and entropy arguments, we report on the pivotal role played by the mutual interactions in the regime of ultra-low-T and vanishing B. Our key results are: i) absence of a genuine zero-field quantum phase transition due to the presence of Bloc; ii) connection between the canonical definition of temperature and Γmag; and iii) possibility of performing adiabatic magnetization by only manipulating the mutual interactions. Our findings unveil unprecedented aspects emerging from the mutual interactions.

7.
J Biomol Struct Dyn ; 25(2): 119-25, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17718590

RESUMO

A stably-bound external binding site for ethidium cation in the major groove of B-form DNA is proposed. This complex is stabilized by hydrogen bonding between this ligand and the nucleophilic centers O6 and N7 of guanine, both of which are accessible via the major groove. This binding site is not the same as the well-characterized electrostatically-stabilized external binding site, but rather is seen to be a covalently bound complex which is stabilized by two hydrogen bonds between the ethidium ligand and guanine in the double stranded (ds) B-form DNA. This site [(1), R. Monaco, F. Hasheer. J Biomol Struct Dyn 10, 675 (1993)] can only exist at very low occupancy ratios. The existence of this binding site leads directly to the expectation that there will exist particular mechanistic steps along the pathway of interaction between ethidium and ds B-DNA at low and high ligand concentrations that involve this binding mode. This would not only explain observations published recently [for example, see (2-6), W. Wilson, I. Lopp. Biopolymers 18, 3025 (1979); L. Wakelin, M. Waring. J Mol Biol 144, 183-214 (1980); A. Karpetyan, N. Mehrabian, G. Terzikian, A. Antonian, P. Vardevanian, M. Frank-Kamenetshii. Proceedings of the 10th Conversation, SUNY Albany, 275 (1998); P. Vardevanyan, A. Antonyan, G. Manukyan, A. Karapetyan. Experimental and Molecular Medicine 33, 205 (2001); P. Vardevanyan, A. Antonyan, L. Minasbekan, A. Karapetyan. Proceedings of the 2002 Miami Nature Biotechnology Winter Symposium, 2(S1), 144 (2002)] but also give insight into discrepancies reported in the literature over the years by different workers studying the mechanism of interaction between ethidium and DNA. In this paper this novel binding interaction is discussed, and it is shown how the elucidation of this interaction led to the proposal of two distinct mechanisms of intercalation between ds B-DNA and ethidium cation for high and low concentrations of ligand. Modeling studies show the stability, configuration, and relative energies of this outside binding site. It is expected that this externally bound complex between ethidium cation and ds B-form DNA will be experimentally detectable using fluorescent polarization and/or linear and circular dichroism spectroscopic studies [(7, 8) E. Tuite, U. Sehlstedt, P. Hagmar, B. Norden, M. Takahashi. Euro J Biochem 243, 482-492 (1997); T. Hard. Biopolymers 26, 613-618 (1987)].


Assuntos
Cátions/química , DNA , Etídio/química , Substâncias Intercalantes/química , Conformação de Ácido Nucleico , Sítios de Ligação , Simulação por Computador , DNA/química , DNA/ultraestrutura , Corantes Fluorescentes/química , Ligação de Hidrogênio , Modelos Químicos , Modelos Moleculares
8.
Neuroimaging Clin N Am ; 17(2): 189-206, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17645970

RESUMO

Different types of malformations share a dilated vein of Galen, but only one of them is a true vein of Galen aneurysmal malformation (VGAM). The optimal window of opportunity for treatment is between 4 and 5 years of months [corrected], because this allows the child to grow and mature. Heart failure and hydrocephalus respond favorably to embolization. Cerebrospinal fluid ventricular shunting, if needed, should be performed after the embolization. The transvenous approach carries significantly elevated morbidity and mortality and is rarely indicated. Anatomic cure of the VGAM is not the main goal of treatment; the ultimate goal is control of the malformation to allow the brain to mature and develop normally.


Assuntos
Veias Cerebrais/anormalidades , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/terapia , Malformações Arteriovenosas Intracranianas/terapia , Adolescente , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/patologia , Criança , Pré-Escolar , Embolização Terapêutica/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Aneurisma Intracraniano/complicações , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Gravidez , Diagnóstico Pré-Natal/métodos , Tomografia Computadorizada por Raios X/métodos
9.
Eura Medicophys ; 43(4): 439-44, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18084165

RESUMO

AIM: To investigate differences in the functional outcome between women sustaining cervical or trochanteric fractures of the hip. METHODS: We studied 684 of 736 women admitted consecutively to a rehabilitation hospital in Italy because of their first hip fracture. Functional recovery was assessed by using Barthel index scores. Fractures were classified as either cervical (n=335) or trochanteric (n=349) on the basis of surgical and radiographic findings. RESULTS: After acute in-patient rehabilitation, women with trochanteric fracture had a significantly lower Barthel index score than women with cervical fracture (median values were 85 and 90 respectively, interquartile ranges were 25 and 30 respectively, P=0.001). Length of stay in the hospital was significantly longer in women with trochanteric fractures (median was 37 days vs 36 days; interquartile range was 10 days vs 8 days, P=0.018). However, the differences between the two groups were no longer significant after adjustment for eight variables that affect functional ability in the same population (i.e., age, pressure ulcers, cognitive impairment, neurologic impairment, infections during the length of stay, bone mineral density, body mass index, and Barthel index scores assessed before rehabilitation). Further-more, we found no significant differences in the change of Barthel index scores during rehabilitation and in Barthel index efficiency (change in the Barthel index score after rehabilitation divided by the length of stay in hospital) between the two groups of women. CONCLUSIONS: After adjustment for several confounders, we did not show significant differences in the functional outcome between women with cervical or trochanteric fracture of the hip.


Assuntos
Fraturas do Quadril/classificação , Fraturas do Quadril/reabilitação , Absorciometria de Fóton , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/epidemiologia , Humanos , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Recuperação de Função Fisiológica , Análise de Regressão , Estatísticas não Paramétricas
10.
Infect Agent Cancer ; 12: 6, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28127386

RESUMO

BACKGROUND: In 2000, an Italian non-governmental organisation (NGO) began a 9-year project to establish a surgical pathology laboratory at the Bugando Medical Centre (BMC) in Mwanza, Tanzania, a country with a low Human Development Index (HDI), and as of 2009, the laboratory was operating autonomously. The present survey aims to evaluate the reproducibility of histological and cytological diagnoses assigned in the laboratory's early years of autonomous activity. We selected a random sample of 196 histological and cytological diagnoses issued in 2010-2011 at the BMC surgical pathology laboratory. The corresponding samples were sent to Italy for review by Italian senior pathologists, who were blinded to the local results. Samples were classified into four diagnostic categories: malignant, benign, inflammatory, and suspicious. The two-observer kappa-statistic for categorised (qualitative) data was then calculated to measure diagnostic concordance between the local Tanzanian pathologists and Italian senior pathologists. The k-Cohen was calculated for concordance in the overall study sample. Concordance and discordance rates were also stratified by subset: general adult, paediatric/adolescent, and lymphoproliferative histopathological diagnoses; fluid and fine needle aspiration (FNA) cytological diagnoses; and PAP tests. Discordance was also categorised by the corresponding hypothetical clinical implications: high, intermediate, and not significant. RESULTS: Overall concordance was 85.2% (167 of 196 diagnoses), with a k-Cohen of 0.7691 (P = 0.0000). Very high concordance was observed in the subsets of adult general pathological diagnoses (90%) and paediatric/adolescent pathological diagnoses (91.18%). Concordance in the subset of PAP tests was 75%, and for fluid/FNA cytological diagnoses it was 56.52%. Concordance among 12 histological subtypes of lymphoma was 75.86%, with substantial discordance observed in the diagnosis of Burkitt lymphoma (five cases diagnosed by Italian pathologists versus 2 by local pathologists). The overall proportion of discordance with high hypothetical clinical implications was 6.1% (12 diagnoses). CONCLUSION: This blind review of diagnoses assigned in Tanzania, a country with low HDI, and in Italy, a country with a very high HDI, seemed to be a sensitive and effective method to identify areas of potential error and may represent a reference point for future, more detailed quality control processes or audits of surgical pathology services located in limited-resource regions.

11.
Eur J Gynaecol Oncol ; 27(3): 313-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16800270

RESUMO

The term female adnexal tumor of probable Wolffian origin "FATWO" designs this tumor wich arises by the rare persisting remnants of the mesonephric duct (Wolffian duct). About 40 cases have been reported in literature. Few cases of recurrence have been reported, FATWO usually shows no signs of hormonal activity. We report a case of the youngest patient affected by FATWO in October 2002. At laparotomy the left adnexa were deformed by a well-capsulated mass, totally removed and sent to the pathologist with a specimen of peritoneal fluid and of the omentum. The histological examination showed a prevalent tubular structure with focal retiform area, without intraluminal mucines. Immunohistochemical findings of the case reported are similar to those described by other authors, except for inhibin which has not been detected by us. The cytofluorimetry showed the low presence of aneuploid cells, with a very low prolifing component (< 1%).


Assuntos
Doenças dos Anexos/patologia , Neoplasias dos Genitais Femininos/patologia , Ductos Mesonéfricos , Doenças dos Anexos/metabolismo , Adulto , Ligamento Largo , Feminino , Citometria de Fluxo , Neoplasias dos Genitais Femininos/metabolismo , Humanos , Imuno-Histoquímica
13.
J Bone Miner Res ; 12(4): 624-31, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9101374

RESUMO

Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17 beta-estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual-energy X-ray absorptiometry [DXA]) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross-links) were assessed at baseline and after 1 and 2 years. In the estrogen-treated group, BMD showed a significant increase (p < 0.001) both after 1 and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2-year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.


Assuntos
Remodelação Óssea , Terapia de Reposição de Estrogênios , Estrogênios/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Administração Cutânea , Idoso , Osso e Ossos/metabolismo , Cálcio/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia
14.
Phys Rev Lett ; 85(16): 3452-5, 2000 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-11030919

RESUMO

In parallel with Kibble's description of the onset of phase transitions in the early Universe, Zurek has provided a simple picture for the onset of phase transitions in condensed matter systems, supported by agreement with experiments in 3He and superconductors. We show how experiments with annular Josephson tunnel junctions can, and do, provide further support for this scenario.

15.
Health Aff (Millwood) ; 14(2): 248-59, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7657246

RESUMO

Rising health care spending, led by rising prices, has had an enormous impact on the economy, especially on the federal budget. Our work shows that if rapid growth in health care prices continues, under current institutional arrangements, real economic growth and employment will be lower during the next two decades than if health price inflation were somehow reduced. How big the losses are and which sectors bear the brunt of the costs vary depending on how society chooses to fund the federal budget deficit that stems from the rising cost of federal health care programs.


Assuntos
Custos de Cuidados de Saúde , Indústrias/economia , Orçamentos , Coleta de Dados , Planos de Assistência de Saúde para Empregados/economia , Humanos , Estados Unidos
16.
AJNR Am J Neuroradiol ; 14(2): 315-21, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8456704

RESUMO

PURPOSE: To draw attention to pseudoaneurysms within ruptured arteriovenous malformations and to consider their diagnostic and therapeutic features, including pitfalls and precautions needed for safe embolization. METHODS: Radiologic and clinical charts of 189 patients who bled from intracranial arteriovenous malformations were retrospectively reviewed. RESULTS: Fifteen of the 189 (8%) were found to have pseudoaneurysms. Nine of the pseudoaneurysms were arterial, six were venous. In the early period following hemorrhage, nine patients were treated conservatively. The other six were treated with surgery (one case) or embolization (five cases) because urgent intervention was required. The clinical outcome for both conservative and interventional groups was generally favorable, but one patient in the conservative group died of a rebleed. In the patients who underwent embolization, the fragile nature of the pseudoaneurysm made it necessary to first embolize the artery feeding it. Embolization with particles was considered hazardous. Instead, free-flow (nonwedged) N-butyl-cyanoacrylate embolization proved safe and effective in treating both the pseudoaneurysms and arteriovenous malformations in these cases. CONCLUSIONS: This study highlights the importance of recognizing pseudoaneurysms in such patients and the importance of using free-flow liquid adhesive material on the artery feeding the pseudoaneurysm if embolization is required.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Adolescente , Adulto , Falso Aneurisma/complicações , Falso Aneurisma/terapia , Angiografia Cerebral , Hemorragia Cerebral/etiologia , Criança , Pré-Escolar , Embolização Terapêutica , Feminino , Humanos , Lactente , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/terapia , Masculino , Radiografia Intervencionista , Estudos Retrospectivos , Ruptura Espontânea , Tomografia Computadorizada por Raios X
17.
J Biomol Struct Dyn ; 14(1): 13-9, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8877557

RESUMO

This research is an effort to further understand the physicochemical interaction between the novel drug molecule diethidium (2,7-diamino 9-[2,7 diamino 10-nN-phenanthridium] 10-nN-phenanthridium) and its biological receptor DNA. The ultimate goal is the elucidation of this novel class of drugs as potential pharmaceutical agents. Understanding the physicochemical properties of this drug as well as the mechanism by which it interacts with DNA should ultimately allow the rational design of novel anti-cancer or anti-viral drugs. A novel binding structure for the diethidium cation to B-form DNA is herein described. Molecular modeling on the complex formed between diethidium and a dodecamer of double-stranded B-form DNA, CGCGAATTCGCG, has shown that this complex is indeed fully capable of participating in the formation of a stable intercalation site. It was expected that diethidium would have a mechanism of intercalation significantly different from other classical intercalators because a) Its structure, that of two perpendicular planes, each known to have excellent intercalation properties, is novel b) The linker region length is zero c) The tilt between the two planes of the drug matches the geometry of the space available to this drug in the major groove. We have studied the complex formed when diethidium enters the central site of the B-DNA dodecamer through the major groove. The complex forms several classes of intercalation structures, which are all stable and vary from "partially intercalated" to "fully intercalated". Multiple minimizations show the drug to be very mobile within the intercalation site. Further, some structures show organization and concomitant stiffening of the DNA above the intercalation site, with a disorganization and disruption of the regular B-DNA structure immediately below the intercalation site. This particular phenomena may be expected to lead to significantly different physicochemical properties for the diethidium complex with respect to other known intercalators, because this sort of vectorial difference in structure above and below the site of intercalation is unknown in existing intercalators, as far as the authors are aware. In addition, we expect the mechanism of interaction between drug and DNA to be described by "direct ligand transfer", wherein the drug is transferred from duplex DNA to duplex DNA without re-entering the solvent. This work is the first instance known to the authors of a novel drug entity that was deduced solely by mathematical reasoning and described subsequently by computational methods. Evidence that diethidium should interact with its target site DNA differently from other known intercalators is strong.


Assuntos
DNA/química , Etídio/análogos & derivados , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Modelos Químicos , Cátions/química , Cátions/metabolismo , Fenômenos Químicos , Físico-Química , Simulação por Computador , DNA/metabolismo , Desenho de Fármacos , Etídio/química , Etídio/metabolismo , Modelos Moleculares , Conformação de Ácido Nucleico
18.
J Biomol Struct Dyn ; 10(4): 675-80, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8466672

RESUMO

Molecular modeling of the system composed of ethidium cation initially intercalated through the major and minor grooves of the B-DNA form of 5'GCATGC3' into the central AT pairs, with the phenyl group oriented either toward or away from the helical axis, led upon energy minimization to intercalation complexes only when the phenyl group was initially oriented away from the helical axis. For the other two cases, energy minimization led to extrusion of the ethidium from the helix to form unanticipated outside-bound complexes stabilized by specific hydrogen bonds. It is suggested that outside-bound major groove complexes involving the GXXXG sequence may play important roles in the reaction mechanism of ethidium intercalation and in its action as a drug.


Assuntos
DNA/química , Etídio/metabolismo , Composição de Bases , Sequência de Bases , Sítios de Ligação , DNA/metabolismo , Ligação de Hidrogênio , Modelos Moleculares , Conformação de Ácido Nucleico
19.
J Biomol Struct Dyn ; 15(1): 63-7, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9283980

RESUMO

Previous research has described the interaction between the novel molecule diethidium (2,7-diamino 9-[2,7 diamino 10-N-phenanthridium] 10-N-phenanthridium) (Figure 1) and B-form DNA. Our goal is the elucidation of diethidium as the first member of a novel class of drugs which are potential pharmaceutical agents. This class of potential drug molecules differs from previously known intercalators in the following ways: a) Its structure, that of two perpendicular planes, each known to have excellent intercalation properties, is novel b) Unlike known bis-intercalators, the linker region length in diethidium is zero c) The geometry of the drug matches the geometry of the space available in the major groove d) The drug is shown to cause some vectorial disruption of DNA. For this paper, we have performed a series of 200 picosecond dynamics simulations on the complex formed between diethidium in the major groove and a dodecarner of double-stranded B-form DNA, CGCGAATTCGCG, and have shown that this complex has a intricate interaction. The DNA dodecamer is found to be in an intermediate A-B state, but, even in simulations as long as 1 nanosecond, the drug does not back-out or otherwise leave the intercalation site. The drug is found to be mobile within the intercalation site on timescales longer than 1 nanoscale. The mobility of the drug within the intercalation site has been predicted by our previous energy minimization studies.


Assuntos
DNA/química , Etídio/análogos & derivados , Substâncias Intercalantes/química , Simulação por Computador , Etídio/química , Modelos Moleculares , Conformação de Ácido Nucleico , Software
20.
Ann Clin Biochem ; 37 ( Pt 6): 781-9, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11085623

RESUMO

Rhesus D (RhD) typing is performed by agglutination methods; however, in clinical situations where these techniques cannot be performed, RhD DNA typing is an alternative approach. The Rh antigens are encoded by the RHD and RHCE genes. In RhD-negative individuals the RHD gene is absent or grossly deleted, but variations in the arrangement of the RH locus in different populations are emerging. The aim of this study was to analyse the gross organization of the RH genes in our population using a previously described multiplex polymerase chain reaction (PCR) method with some modifications. We studied 253 DNA samples from Argentinian blood donors, 15 samples with a reduced expression of the D antigen and 1 Dc- phenotype. We evaluated the clinical utility of this method to ascertain the RhD antigen in 10 patients with warm-type autoimmune haemolytic anaemia (AIHA) and 14 samples of amniotic fluids. All Rh phenotypes were properly characterized and no discrepancies with serological typing were found. Analyses performed in the Dc- phenotype suggest the presence of a hybrid RHCE-RHD gene. DNA typing confirmed the RhD-negative type of one AIHA sample in which serological tests were inconclusive. Foetal DNA typing correctly indicated the RhD in every foetus. VNTR (variable number of tandem repeats) and STR (short tandem repeats) analysis detected maternal contamination in two amniocentesis samples and confirmed the foetal origin of 12. This multiplex PCR strategy is suitable for RhD determination in clinical situations in which serological typing cannot be accomplished with its usual ease.


Assuntos
Anemia Hemolítica Autoimune/sangue , DNA/análise , Sistema do Grupo Sanguíneo Rh-Hr/genética , Alelos , Líquido Amniótico/química , Líquido Amniótico/fisiologia , Teste de Coombs , Primers do DNA/química , Glicoproteínas/genética , Humanos , Repetições Minissatélites/genética , Fenótipo , Reação em Cadeia da Polimerase , Mapeamento por Restrição , Testes Sorológicos , Sequências de Repetição em Tandem/genética
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