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1.
Phys Rev Lett ; 127(15): 151301, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34678017

RESUMO

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

2.
Phys Rev Lett ; 121(22): 221301, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30547645

RESUMO

We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at 220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.

3.
Pediatr Obes ; 13(11): 677-685, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30156058

RESUMO

BACKGROUND: Obesity is a major and worldwide health problem in children. OBJECTIVES: The Early Childhood Obesity Prevention Program is a multi-component, randomized, controlled trial of a pilot community-focused obesity prevention program for mother/newborn dyads. METHODS: Underserved, mother/newborn dyads were recruited to receive a standard home visitation program (Nurturing Families Network, NFN) or an enhanced program (NFN+) that incorporated behavioural change strategies (e.g., goal-setting, problem-solving) and focused on six obesity-associated behaviours (breastfeeding, juice/sugar-sweetened beverages, solids, infant sleep, TV/screen time and soothability) with linkages to community resources. Weight-for-length (WFL) z-score and maternal diet were secondary outcomes. RESULTS: Fifty-seven dyads were recruited and 47 fully eligible dyads were enrolled (NFN = 21, NFN+ = 26). Forty-one (87.2%) were assessed at 6 months and 34 (72.3%) at 12 months. Retention at 12 months was higher for NFN+ dyads (84.6% vs. 56.1%, p = 0.04). NFN+ mothers were more likely to continue breastfeeding at 6 and 12 months vs. NFN mothers (p = 0.03 and 0.003, respectively), and at 12 months, NFN+ infants had fewer nocturnal awakenings (p = 0.04). There were no differences in other primary outcome measures or in WFL z-score at 6 or 12 months. CONCLUSIONS: A multi-component behavioural intervention increased breastfeeding duration and decreased nocturnal awakenings in infants of low-income families.


Assuntos
Terapia Comportamental/métodos , Comportamentos Relacionados com a Saúde , Obesidade Infantil/prevenção & controle , Adulto , Aleitamento Materno/estatística & dados numéricos , Criança , Pré-Escolar , Dieta , Feminino , Seguimentos , Estilo de Vida Saudável , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Projetos Piloto , Pobreza , Avaliação de Programas e Projetos de Saúde/métodos , Inquéritos e Questionários
4.
Appl Radiat Isot ; 128: 165-170, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28728069

RESUMO

A chemical separation technique for removing interfering gamma-ray radionuclides by combined precipitation of Nb pentoxide and anion exchange was proposed, thereby allowing detection of trace 94Nb in low-level radwastes. The detection limit for 94Nb was improved by a factor of 10-103, and the scaling factor (94Nb/60Co) of the radwastes was estimated to be less than 10-5. This technique can be used for low-level radwaste classification and power reactor decommissioning.

5.
Pediatr Diabetes ; 18(5): 327-331, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28568353

RESUMO

Prior to 1971, type Ia glycogen storage disease was marked by life-threatening hypoglycemia, lactic acidosis, severe failure to thrive, and developmental delay. With the introduction of continuous feeds in the 1970s and cornstarch in the 1980s, the prognosis improved, but complications almost universally developed. Changes in the management of type Ia glycogen storage disease have resulted in improved metabolic control, and this manuscript reviews the increasing evidence that complications can be delayed or prevented with optimal metabolic control as previously was seen in diabetes.


Assuntos
Doença de Depósito de Glicogênio Tipo I/terapia , Medicina de Precisão , Insuficiência Renal/prevenção & controle , Adenoma/complicações , Adenoma/prevenção & controle , Adulto , Criança , Terapia Combinada , Doença de Depósito de Glicogênio Tipo I/sangue , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Humanos , Hipoglicemia/complicações , Hipoglicemia/prevenção & controle , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/prevenção & controle , Nefrocalcinose/complicações , Nefrocalcinose/prevenção & controle , Nefrolitíase/complicações , Nefrolitíase/prevenção & controle , Osteoporose/complicações , Osteoporose/prevenção & controle , Prognóstico , Insuficiência Renal/complicações
6.
Int J Oral Maxillofac Surg ; 45(11): 1459-1463, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27364371

RESUMO

Classic cinch suture narrowing of the nasal alar base by medially suturing the bilateral nasolabial soft tissue with one long suture has a limited effect. The modified cinch method described in the present study anchors non-absorbable sutures to the bilateral lower border of the piriform rim and provides optimal direction, position, and stability. The sutures can be shortened and the strength kept stable while the surgical wounds heal. Separate bilateral sutures can also reduce interference and distortion from nasotracheal intubation and make the nasolabial profile more symmetrical. Seventeen consecutive cases of maxillary Le Fort I osteotomy were analyzed. The nasal and alar base width changes were 0.4±1.2mm and 0.1±1.1mm, respectively, and the widening rate was only 1.1%. Compared with the results of other studies, postoperative nasal flaring was well controlled using the modified cinch suture anchored to the bilateral lower border of the piriform rim described in this study.


Assuntos
Maxila/cirurgia , Cartilagens Nasais/cirurgia , Osteotomia de Le Fort , Técnicas de Sutura , Adulto , Feminino , Humanos , Masculino , Fotografação , Adulto Jovem
7.
Allergy ; 71(11): 1626-1631, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27286483

RESUMO

BACKGROUND: An individual's birth month has been associated with allergic diseases, but little is known about the association between birth month and atopic dermatitis (AD). OBJECTIVE: The aim of this study was to investigate the risk of AD in children born in various months. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a case-control study that included 31 237 AD cases and 124 948 age- and gender-matched controls without AD. Data regarding sociodemographic factors and coexisting medical conditions were collected and controlled in the multivariate logistic regression to determine the adjusted odds ratios and 95% confidence intervals for AD associated with the participant's birth month. RESULTS: Compared with people born in May, people born in December had the highest risk of AD (OR 1.17, 95% CI 1.10-1.25), followed by people born in October (OR 1.15, 95% CI 1.08-1.22) and November (OR 1.13, 95% CI 1.06-1.20). Low income (OR 1.28), asthma (OR 1.88), allergic rhinitis (OR 1.70), psoriasis (OR 2.36), vitiligo (OR 1.99), urticaria (OR 2.14), and systemic lupus erythematosus (OR 1.91) were significant coexisting medical conditions associated with AD. CONCLUSION: Being born in December, October, or November may be associated with an increased risk of AD. Future investigations are needed to evaluate the possible mechanism behind the association between birth month and AD.


Assuntos
Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Parto , Vigilância da População , Estações do Ano , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Razão de Chances , Prevalência , Fatores Socioeconômicos , Taiwan/epidemiologia , Adulto Jovem
8.
Phys Rev Lett ; 116(3): 031302, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26849583

RESUMO

We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross-spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed ΛCDM is detected at modest significance in the 95×150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23×95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23×353. We take the likelihood of all the spectra for a multicomponent model including lensed ΛCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves.

9.
J Laryngol Otol ; 129(12): 1201-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26490496

RESUMO

OBJECTIVE: To evaluate the chance of improvement and risk of decline in olfaction among patients with post-traumatic olfactory loss. METHODS: This study comprised 80 patients. Changes in olfaction were determined using a visual analogue scale and the 'Sniffin' Sticks' test. Logistic regression was used to identify predictors for olfactory changes. RESULTS: Olfactory changes were observed in 9-35 per cent of patients. The rates of improvement and decline according to visual analogue scale scores were 35 per cent and 10 per cent respectively, whereas those in the Sniffin' Sticks test were 9 per cent and 11 per cent respectively. There was a predictive link between non-anosmia and decline in Sniffin' Sticks test scores (odds ratio = 16.61, p = 0.003). A positive correlation was observed between the scores in the first and last examinations (rho = 0.532, p < 0.001). CONCLUSION: Patients should be informed that they may experience an improvement or decline in olfaction following post-traumatic olfactory dysfunction. This study provides evidence to support comprehensive counselling regarding prognosis as an integral part of management strategies.


Assuntos
Traumatismos Craniocerebrais/complicações , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Traumatismos Craniocerebrais/diagnóstico , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Transtornos do Olfato/epidemiologia , Prognóstico , Qualidade de Vida , Remissão Espontânea , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Adulto Jovem
10.
Phys Rev Lett ; 112(24): 241101, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24996078

RESUMO

We report results from the BICEP2 experiment, a cosmic microwave background (CMB) polarimeter specifically designed to search for the signal of inflationary gravitational waves in the B-mode power spectrum around ℓ∼80. The telescope comprised a 26 cm aperture all-cold refracting optical system equipped with a focal plane of 512 antenna coupled transition edge sensor 150 GHz bolometers each with temperature sensitivity of ≈300 µK(CMB)√s. BICEP2 observed from the South Pole for three seasons from 2010 to 2012. A low-foreground region of sky with an effective area of 380 square deg was observed to a depth of 87 nK deg in Stokes Q and U. In this paper we describe the observations, data reduction, maps, simulations, and results. We find an excess of B-mode power over the base lensed-ΛCDM expectation in the range 30 < ℓ < 150, inconsistent with the null hypothesis at a significance of >5σ. Through jackknife tests and simulations based on detailed calibration measurements we show that systematic contamination is much smaller than the observed excess. Cross correlating against WMAP 23 GHz maps we find that Galactic synchrotron makes a negligible contribution to the observed signal. We also examine a number of available models of polarized dust emission and find that at their default parameter values they predict power ∼(5-10)× smaller than the observed excess signal (with no significant cross-correlation with our maps). However, these models are not sufficiently constrained by external public data to exclude the possibility of dust emission bright enough to explain the entire excess signal. Cross correlating BICEP2 against 100 GHz maps from the BICEP1 experiment, the excess signal is confirmed with 3σ significance and its spectral index is found to be consistent with that of the CMB, disfavoring dust at 1.7σ. The observed B-mode power spectrum is well fit by a lensed-ΛCDM+tensor theoretical model with tensor-to-scalar ratio r = 0.20_(-0.05)(+0.07), with r = 0 disfavored at 7.0σ. Accounting for the contribution of foreground, dust will shift this value downward by an amount which will be better constrained with upcoming data sets.

11.
J Laryngol Otol ; 127(4): 415-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23448530

RESUMO

OBJECTIVE: We report a rare case of concurrent myeloid sarcoma and acute fulminant invasive fungal sinusitis in a patient with relapsed acute myeloid leukaemia. CASE REPORT: A 73-year-old man was diagnosed with acute myeloid leukaemia and developed relapse one year later. After two courses of azacytidine, he began suffering from a dull pain in the left temporal and orbital regions. Sinus computed tomography showed a localised lesion in the left ethmoid sinus, which rapidly progressed to an extensive intracranial mass within one month. Surgical debridement was performed, and histopathological analysis revealed the coexistence of myeloid sarcoma and acute fulminant invasive fungal sinusitis. The patient responded well to prompt surgical debridement, antifungal medication and radiotherapy. CONCLUSION: Coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis poses an urgent diagnostic and management challenge to clinicians. Timely recognition of this rare comorbid condition is warranted as application of appropriate treatment can save lives.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Micoses/diagnóstico , Sarcoma Mieloide/diagnóstico , Sinusite/diagnóstico , Idoso , Antifúngicos/uso terapêutico , Comorbidade , Desbridamento , Diagnóstico Diferencial , Fungos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Micoses/tratamento farmacológico , Seios Paranasais , Sarcoma Mieloide/tratamento farmacológico , Sinusite/tratamento farmacológico
12.
Eur J Clin Nutr ; 61(8): 996-1003, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17228344

RESUMO

OBJECTIVE: Plasma B-group vitamins and age may affect the carotid intima-media thickness (IMT) in subjects with different 677TT genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. DESIGN: A hospital-based cross-study. SETTING: Genomic and Vascular Center, Changhua Christian Hospital, Changhua, Taiwan. SUBJECTS: Five hundred and forty-one clinically healthy subjects. INTERVENTION: Fasting plasma, homocysteine (Hcy), vitamin B(6), vitamin B(12), folate and B-mode carotid ultrasound. RESULTS: MTHFR genotype, plasma concentrations of folate, vitamin B(6) and vitamin B(12) and age were significantly correlated to the plasma Hcy concentration. MTHFR 677TT carriers had higher concentrations of Hcy than did subjects with the CC and CT genotypes. Age, sex, body mass index and plasma Hcy were independent contributors to increase carotid IMT. However, with stratification by mean value of age and B-group vitamins concentrations, we found that at advanced age, lower plasma folate and vitamin B(12) were three risk factors involved in the enhancing effect of the MTHFR 677TT genotype on the increase of plasma Hcy and carotid IMT. CONCLUSION: MTHFR 677TT-related carotid atherosclerosis was only identified in healthy elderly subjects with lower level of plasma folate and vitamin B(12). SPONSORSHIP: Changhua Christian Hospital.


Assuntos
Carbono-Nitrogênio Ligases/genética , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/genética , Polimorfismo Genético , Túnica Íntima/patologia , Complexo Vitamínico B/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/sangue , Estudos Transversais , Feminino , Ácido Fólico/sangue , Genótipo , Homocisteína/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Vitamina B 12/sangue
13.
Br J Ophthalmol ; 89(11): 1468-73, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16234455

RESUMO

AIMS: To compare the in vitro killing effect of different agents on Demodex and to report the in vivo killing effect of tea tree oil (TTO) on ocular Demodex. METHODS: Survival time of Demodex was measured under the microscope. Sampling and counting of Demodex was performed by a modified method. RESULTS: Demodex folliculorum survived for more than 150 minutes in 10% povidone-iodine, 75% alcohol, 50% baby shampoo, and 4% pilocarpine. However, the survival time was significantly shortened to within 15 minutes in 100% alcohol, 100% TTO, 100% caraway oil, or 100% dill weed oil. TTO's in vitro killing effect was dose dependent. Lid scrub with 50% TTO, but not with 50% baby shampoo, can further stimulate Demodex to move out to the skin. The Demodex count did not reach zero in any of the seven patients receiving daily lid scrub with baby shampoo for 40-350 days. In contrast, the Demodex count dropped to zero in seven of nine patients receiving TTO scrub in 4 weeks without recurrence. CONCLUSIONS: Demodex is resistant to a wide range of antiseptic solutions. Weekly lid scrub with 50% TTO and daily lid scrub with tea tree shampoo is effective in eradicating ocular Demodex.


Assuntos
Infecções Oculares Parasitárias/tratamento farmacológico , Doenças Palpebrais/tratamento farmacológico , Infestações por Ácaros/tratamento farmacológico , Fitoterapia , Óleo de Melaleuca/uso terapêutico , Animais , Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/uso terapêutico , Relação Dose-Resposta a Droga , Infecções Oculares Parasitárias/parasitologia , Infecções Oculares Parasitárias/patologia , Pestanas/parasitologia , Pestanas/patologia , Doenças Palpebrais/parasitologia , Doenças Palpebrais/patologia , Humanos , Técnicas In Vitro , Infestações por Ácaros/parasitologia , Infestações por Ácaros/patologia , Ácaros/efeitos dos fármacos , Óleo de Melaleuca/farmacologia
14.
J Clin Pharm Ther ; 29(3): 279-98, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15153091

RESUMO

BACKGROUND: From the deductive point of view, neurotransmitter receptors can be divided into categories such as cholinergic (muscarinic, nicotinic), adrenergic (alpha- and beta-), dopaminergic, serotoninergic (5-HT1 approximately 5-HT5), and histaminergic (H1 and H2). Selective agonists and antagonists of each receptor subtype can have specific useful therapeutic applications. For understanding the molecular mechanisms of action, an inductive method of analysis is useful. OBJECTIVE: The aim of the present study is to examine the structure-activity relationships of agents acting on G-protein coupled receptors. METHOD: Representative sets of G-PCR agonists and antagonists were identified from the literature and Medline [P.M. Walsh (2003) Physicians' Desk Reference; M.J. O'Neil (2001) The Merck Index]. The molecular weight (MW), calculated logarithm of octanol/water partition coefficient (C log P) and molar refraction (CMR), dipole moment (DM), E(lumo) (the energy of the lowest unoccupied molecular orbital, a measure of the electron affinity of a molecule and its reactivity as an electrophile), E(homo) (the energy of the highest occupied molecular orbital, related to the ionization potential of a molecule, and its reactivity as a nucleophile), and the total number of hydrogen bonds (H(b)) (donors and receptors), were chosen as molecular descriptors for SAR analyses. RESULTS: The data suggest that not only do neurotransmitters share common structural features but their receptors belong to the same ensemble of G-protein coupled receptor with seven to eight transmembrane domains with their resultant dipoles in an antiparallel configuration. Moreover, the analysis indicates that the receptor exists in a dynamic equilibrium between the closed state and the open state. The energy needed to open the closed state is provided by the hydrolysis of GTP. A composite 3-D parameter frame setting of all the neurotransmitter agonists and antagonists are presented using MW, Hb and mu as independent variables. CONCLUSION: It appears that all neurotransmitters examined in this study operate by a similar mechanism with the G-protein coupled receptors.


Assuntos
Neurotransmissores/antagonistas & inibidores , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/fisiologia , Relação Estrutura-Atividade , Agonistas Adrenérgicos/química , Agonistas Adrenérgicos/classificação , Antagonistas Adrenérgicos/química , Antagonistas Adrenérgicos/classificação , Fenômenos Químicos , Físico-Química , Agonistas Colinérgicos/química , Agonistas Colinérgicos/classificação , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/classificação , Agonistas de Dopamina/química , Agonistas de Dopamina/classificação , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/química , Antagonistas de Dopamina/classificação , Antagonistas de Dopamina/farmacologia , Agonistas dos Receptores Histamínicos/química , Agonistas dos Receptores Histamínicos/classificação , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/química , Antagonistas dos Receptores Histamínicos/classificação , Antagonistas dos Receptores Histamínicos/farmacologia , Modelos Biológicos , Estrutura Molecular , Neurotransmissores/agonistas , Neurotransmissores/química , Receptores Adrenérgicos/classificação , Receptores Adrenérgicos/efeitos dos fármacos , Receptores Adrenérgicos/fisiologia , Receptores Colinérgicos/classificação , Receptores Colinérgicos/efeitos dos fármacos , Receptores Colinérgicos/fisiologia , Receptores Histamínicos/classificação , Receptores Histamínicos/efeitos dos fármacos , Receptores Histamínicos/fisiologia , Antagonistas da Serotonina/química , Antagonistas da Serotonina/classificação , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/classificação , Agonistas do Receptor de Serotonina/farmacologia
15.
J Clin Pharm Ther ; 28(3): 203-28, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12795780

RESUMO

OBJECTIVE: A large number of structurally and functionally diverse compounds act as substrates or modulators of p-glycoprotein (p-gp). Some of them possess multiple drug resistance (MDR)-reversing activity, but only a small number of them have entered clinical study. In order to uncover the factors which exert a significant impact on the interaction between substrates/modulators and p-gp, we have performed structure-activity relationship (SAR) analyses, including molecular modelling, two-dimensional (2D) and three-dimensional (3D) parameter-frame-setting analysis, quantitative structure activity relationship (QSAR) analysis among substrates/modulators, as well as clinically promising MDR-reversing agents. METHODS: The physicochemical parameters C log P, CMR and all regression equations were derived by using C log P version 4.0 and the latest CQSAR software, respectively. Molecular modelling and all other parameter calculations were performed by using HyperChem version 5.0 program, after geometry optimization and energy minimization using the AM1 semiempirical method. RESULTS: SAR analyses indicate that MDR reversal activity is correlated with the lipophilicity (C log P), molecular weight (log Mw), longest chain (Nlc) of the molecule and the energy of the highest occupied orbital (Ehomo). In addition, the presence of a basic tertiary nitrogen atom in the structure is also an important contributor to p-gp inhibitory activity. Some separation in space is achieved for different subsets of p-gp substrates and inhibitors using Nlc, C log P and Ehomo as three independent parameters in the 3D-parameter-frame setting. CONCLUSION: A highly effective p-gp modulator candidate should possess a log P value of 2.92 or higher, 18-atom-long or longer molecular axis, and a high Ehomo value, as well as at least one tertiary basic nitrogen atom. The results obtained may be useful in explaining drug-p-gp interactions for different compounds, including drug interactions and the development of new MDR chemosensitizers.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Flavonoides/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/efeitos da radiação , Proteínas de Transporte/fisiologia , Flavonoides/química , Humanos , Modelos Moleculares , Estrutura Molecular , Piperidinas/química , Piperidinas/metabolismo , Proteína Quinase C/fisiologia , Piridinas/química , Piridinas/metabolismo , Análise de Regressão , Relação Estrutura-Atividade
17.
J Urol ; 167(6): 2594-7, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11992093

RESUMO

PURPOSE: We have previously developed and reported an ultrasound based real-time tracking system for renal stones. In the current study we continued to verify the reliability of this tracking system by a simulated animal test. MATERIALS AND METHODS: We used 13 prerecorded ultrasound stone trajectories to test the system. The real-time tracking system was implemented on the Litemed 9200 electrohydraulic lithotriptor (LiteMed Co., Taipei, Taiwan). An artificial stone and tap water were sealed in a balloon. The balloon was inserted into the pelvis of a pig kidney. While the kidney was affixed to and moved by a simulator, it was immersed in a specifically designed simulated animal model tank containing tap water. The stone was localized by ultrasound. The kidney was moved by the simulator according to a prerecorded stone trajectory. A total of 3,000 shock waves were delivered to the stone. For each recorded stone trajectory experiments were done under nontracking and tracking conditions. We performed tests of the fragment-to-weight ratio, which denotes the performance of a shock wave lithotriptor when fragmenting a stone. RESULTS: The mean fragment-to-weight ratio was 55.3% +/- 25.9% in the nontracking and 100% +/- 0% in the tracking group. The difference in these 2 groups was statistically significant (paired t test p <0.01). CONCLUSIONS: The ultrasound based real-time tracking system proved to improve the performance of a shock wave lithotriptor significantly when fragmenting stones in a simulated animal test. We believe that the tracking system would greatly reduce the number of shocks and time needed for treating renal stones.


Assuntos
Cálculos Renais/terapia , Litotripsia , Ultrassonografia de Intervenção , Animais , Técnicas In Vitro , Cálculos Renais/diagnóstico por imagem , Modelos Anatômicos , Suínos
18.
Biol Pharm Bull ; 24(11): 1311-5, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11725970

RESUMO

A protocol for de novo regeneration and rapid micropropagation of Scrophularia yoshimurae (Scrophulariaceae) has been developed. Multiple shoot development was achieved by culturing the shoot-tip, leaf-base, stem-node and stem-internode explants on Murashige and Skoog (MS) medium supplemented with 4.44 microM N6-benzyladenine (BA) and 1.07 microM alpha-naphthaleneacetic acid (NAA). Stem-node and shoot-tip explants showed the highest response (100%) followed by stem-internode (74.4%) and leaf-base (7.7%) explants. The shoots were multiplied by subculturing on the same medium used for shoot induction. Shoots were rooted on growth regulator-free MS basal medium and the plantlets were transplanted to soil and acclimatized in the growth chamber. The content of harpagoside, a quantitatively predominant iridoid glycoside, in different plant material was determined by high performance liquid chromatography (HPLC). The analysis revealed that the content of harpagoside in the aerial and underground parts of S. yoshimurae was significantly higher than the marketed crude drug (underground parts of Scrophularia ningpoensis).


Assuntos
Glucosídeos/análise , Glicosídeos/análise , Piranos/análise , Regeneração/fisiologia , Scrophulariaceae/química , Scrophulariaceae/fisiologia , Cromatografia Líquida de Alta Pressão/métodos , Técnicas de Cultura/métodos , Glicosídeos/fisiologia , Iridoides , Extratos Vegetais/análise , Raízes de Plantas/química , Raízes de Plantas/fisiologia , Brotos de Planta/química , Brotos de Planta/fisiologia
20.
J Urol ; 166(1): 28-32, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11435816

RESUMO

PURPOSE: We developed a real-time tracking system for renal stones that decreases the number of shock waves and treatment time of shock wave lithotripsy. MATERIALS AND METHODS: Ultrasound images were analyzed to identify the renal stones. A computer software module for ultrasound image processing was developed to monitor stone location instantaneously. Another computer software module controlled generator movement in real time for tracking the stone. We used 13 ultrasound stone trajectories recorded from patients to test the system in vitro. Two tests were established to verify tracking system reliability. One test focused on improvement in the coincidence ratio, which denotes the matching extent of the stone within the effective focal area. The other test focused on improvement in the efficiency ratio, that is a decrease in the number of shocks for stone fragmentation. For each recorded stone trajectory 2 experiments were done under tracking and nontracking conditions. RESULTS: The average coincidence and efficiency ratios plus or minus standard deviation were 79.6% +/- 9.8% and 45.0% +/- 12.7% without tracking, and 97.0% +/- 3.0% and 85.5 +/- 6.8% with tracking, respectively. All tests were statistically significant (paired t test p <0.01). CONCLUSIONS: An ultrasound based real-time tracking system proved to be significantly helpful for in vitro lithotripsy. It appears that the tracking system may greatly decrease the number of shocks and treatment time for renal stones.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/terapia , Litotripsia/métodos , Seguimentos , Humanos , Monitorização Fisiológica , Movimento , Sensibilidade e Especificidade , Fatores de Tempo , Ultrassonografia
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