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1.
Child Dev ; 91(2): e345-e364, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30937897

RESUMO

A multifaceted, relationally focused intervention involving group and individual pre- and postnatal counseling, print resources, and community resources encouraged 390 fathers of newborn infants in Vietnam to responsively support mothers and work with them as a parenting team. Both partners completed questionnaires prebirth and 1-, 4-, and 9-months postbirth on measures of breastfeeding support, exclusive breastfeeding duration, relationship quality, and infant development. Compared to 412 comparison group couples, intervention couples evidenced greater father support, especially in terms of helping and responsiveness to the mother's needs. This support predicted longer exclusive breastfeeding duration, improved relationship quality, and higher levels of infant development at 9 months. Sensitively working together with mothers as a coordinated team enhanced couple's relationship functioning and improved children's developmental outcomes.


Assuntos
Aconselhamento , Relações Pai-Filho , Relações Mãe-Filho , Poder Familiar/psicologia , Adulto , Aleitamento Materno/estatística & dados numéricos , Desenvolvimento Infantil , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Vietnã
2.
Anticancer Agents Med Chem ; 19(12): 1543-1557, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31267876

RESUMO

BACKGROUND: Target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development worldwide, and Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. AIMS: This study aims at developing novel HDAC inhibitors bearing quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. METHODS: A series of novel N-hydroxyheptanamides incorporating 6-hydroxy-2 methylquinazolin-4(3H)-ones (14a-m) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2 (liver cancer), MCF-7 (breast cancer) and SKLu-1 (lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships. ADME-T predictions for selected compounds were also performed to predict some important features contributing to the absorption profile of the present hydroxamic derivatives. RESULTS: It was found that the N-hydroxyheptanamide 14i and 14j were the most potent, both in terms of HDAC inhibition and cytotoxicity. These compounds displayed up to 21-71-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in terms of cytotoxicity, and strong inhibition against the whole cell HDAC enzymes with IC50 values of 7.07-9.24µM. Docking experiments on HDAC2 isozyme using Autodock Vina showed all compounds bound to HDAC2 with relatively higher affinities (from -7.02 to -11.23 kcal/mol) compared to SAHA (-7.4 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward breast cancer cells (MCF-7) than liver (HepG2), and lung (SKLu-1) cancer cells.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinazolinas/química , Relação Estrutura-Atividade
3.
Glob Health Action ; 8: 27554, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26160770

RESUMO

BACKGROUND: Vietnam has achieved great improvements in maternal healthcare outcomes, but there is evidence of increasing inequity. Disadvantaged groups, predominantly ethnic minorities and people living in remote mountainous areas, do not gain access to maternal health improvements despite targeted efforts from policymakers. OBJECTIVE: This study identifies underlying structural barriers to equitable maternal health care in Nghe An province, Vietnam. Experiences of social inequity and limited access among child-bearing ethnic and minority women are explored in relation to barriers of care provision experienced by maternal health professionals to gain deeper understanding on health outcomes. DESIGN: In 2012, 11 focus group discussions with women and medical care professionals at local community health centers and district hospitals were conducted using a hermeneutic-dialectic method and analyzed for interpretation using framework analysis. RESULTS: The social determinants 'limited negotiation power' and 'limited autonomy' orchestrate cyclical effects of shared marginalization for both women and care professionals within the provincial health system's infrastructure. Under-staffed and poorly equipped community health facilities refer women and create overload at receiving health centers. Limited resources appear diverted away from local community centers as compensation to the district for overloaded facilities. Poor reputation for low care quality exists, and professionals are held in low repute for causing overload and resulting adverse outcomes. Country-wide reforms force women to bear responsibility for limited treatment adherence and health insight, but overlook providers' limited professional development. Ethnic minority women are hindered by relatives from accessing care choices and costs, despite having advanced insight about government reforms to alleviate poverty. Communication challenges are worsened by non-existent interpretation systems. CONCLUSIONS: For maternal health policy outcomes to become effective, it is important to understand that limited negotiation power and limited autonomy simultaneously confront childbearing women and health professionals. These two determinants underlie the inequitable economic, social, and political forces in Vietnam's disadvantaged communities, and result in marginalized status shared by both in the poorest sectors.


Assuntos
Acessibilidade aos Serviços de Saúde/organização & administração , Disparidades em Assistência à Saúde/etnologia , Serviços de Saúde Materna/organização & administração , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Determinantes Sociais da Saúde/etnologia , Adulto , Feminino , Grupos Focais , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/normas , Humanos , Masculino , Serviços de Saúde Materna/normas , Autonomia Pessoal , Qualidade da Assistência à Saúde/organização & administração , Características de Residência , Fatores Socioeconômicos , Vietnã
4.
Comput Methods Programs Biomed ; 113(1): 153-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24184112

RESUMO

An abdominal wall hernia is a protrusion of the intestine through an opening or area of weakness in the abdominal wall. Correct pre-operative identification of abdominal wall hernia meshes could help surgeons adjust the surgical plan to meet the expected difficulty and morbidity of operating through or removing the previous mesh. First, we present herein for the first time the application of image analysis for automated identification of hernia meshes. Second, we discuss the novel development of a new entropy-based image texture feature using geostatistics and indicator kriging. Third, we seek to enhance the hernia mesh identification by combining the new texture feature with the gray-level co-occurrence matrix feature of the image. The two features can characterize complementary information of anatomic details of the abdominal hernia wall and its mesh on computed tomography. Experimental results have demonstrated the effectiveness of the proposed study. The new computational tool has potential for personalized mesh identification which can assist surgeons in the diagnosis and repair of complex abdominal wall hernias.


Assuntos
Hérnia Ventral/diagnóstico por imagem , Telas Cirúrgicas , Tomografia Computadorizada por Raios X , Humanos , Probabilidade
5.
Eur J Neurosci ; 20(2): 441-58, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15233753

RESUMO

Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons. It was located mostly on the membrane surface of intracellular organelles known to store Ca(2+) (e.g. mitochondria, smooth endoplasmic reticulum), less frequently on the somatic or dendritic plasma membrane. MGL immunoreactivity was found in axon terminals of granule cells, CA3 pyramidal cells and some interneurons. In the cerebellum, Purkinje cells and their dendrites are intensively immunoreactive for FAAH, together with a sparse axon plexus at the border of the Purkinje cell/granule cell layers. Immunostaining for MGL was complementary, the axons in the molecular layer were intensively labelled leaving the Purkinje cell dendrites blank. FAAH distribution in the amygdala was similar to that of the CB(1) cannabinoid receptor: evident signal in neuronal somata and proximal dendrites in the basolateral nucleus, and hardly any labelling in the central nucleus. MGL staining was restricted to axons in the neuropil, with similar relative signal intensities seen for FAAH in different nuclei. Thus, FAAH is primarily a postsynaptic enzyme, whereas MGL is presynaptic. FAAH is associated with membranes of cytoplasmic organelles. The differential compartmentalization of the two enzymes suggests that anandamide and 2-AG signalling may subserve functional roles that are spatially segregated at least at the stage of metabolism.


Assuntos
Amidoidrolases/metabolismo , Tonsila do Cerebelo/enzimologia , Cerebelo/enzimologia , Hipocampo/enzimologia , Monoacilglicerol Lipases/metabolismo , Terminações Pré-Sinápticas/enzimologia , Sinapses/enzimologia , Amidoidrolases/genética , Tonsila do Cerebelo/ultraestrutura , Animais , Calbindina 2 , Calbindinas , Cerebelo/ultraestrutura , Colecistocinina/metabolismo , Imunofluorescência/métodos , Glutamato Descarboxilase/metabolismo , Hipocampo/ultraestrutura , Isoenzimas/metabolismo , Masculino , Camundongos , Camundongos Knockout , Microscopia Imunoeletrônica/métodos , Parvalbuminas/metabolismo , Ratos , Ratos Wistar , Proteína G de Ligação ao Cálcio S100/metabolismo , Sinapses/ultraestrutura
6.
Proc Natl Acad Sci U S A ; 99(16): 10819-24, 2002 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-12136125

RESUMO

The endogenous cannabinoids (endocannabinoids) are lipid molecules that may mediate retrograde signaling at central synapses and other forms of short-range neuronal communication. The monoglyceride 2-arachidonoylglycerol (2-AG) meets several criteria of an endocannabinoid substance: (i) it activates cannabinoid receptors; (ii) it is produced by neurons in an activity-dependent manner; and (iii) it is rapidly eliminated. 2-AG inactivation is only partially understood, but it may occur by transport into cells and enzymatic hydrolysis. Here we tested the hypothesis that monoglyceride lipase (MGL), a serine hydrolase that converts monoglycerides to fatty acid and glycerol, participates in 2-AG inactivation. We cloned MGL by homology from a rat brain cDNA library. Its cDNA sequence encoded for a 303-aa protein with a calculated molecular weight of 33,367 daltons. Northern blot and in situ hybridization analyses revealed that MGL mRNA is heterogeneously expressed in the rat brain, with highest levels in regions where CB(1) cannabinoid receptors are also present (hippocampus, cortex, anterior thalamus, and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased MGL expression and attenuated N-methyl-D-aspartate/carbachol-induced 2-AG accumulation in these cells. No such effect was observed on the accumulation of anandamide, another endocannabinoid lipid. The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons.


Assuntos
Encéfalo/enzimologia , Glicerídeos/metabolismo , Monoacilglicerol Lipases/metabolismo , Sequência de Aminoácidos , Animais , Ácidos Araquidônicos/metabolismo , Sequência de Bases , Encéfalo/citologia , Células COS , Moduladores de Receptores de Canabinoides , Canabinoides/metabolismo , Células Cultivadas , Chlorocebus aethiops , DNA Complementar , Endocanabinoides , Expressão Gênica , Células HeLa , Humanos , Hidrólise , Dados de Sequência Molecular , Monoacilglicerol Lipases/genética , Neurônios/citologia , Neurônios/enzimologia , Alcamidas Poli-Insaturadas , Ratos , Ratos Wistar
7.
Am J Physiol Regul Integr Comp Physiol ; 279(6): R2208-13, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11080087

RESUMO

The addition to the respiratory system of a resistive load results in breathing pattern changes and in negative intrathoracic pressure increases. The aim of this study was to use resistive load breathing as a stimulus to the cardiorespiratory interaction and to examine the extent of the changes in heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) in relation to the breathing pattern changes. HRV and RSA were studied in seven healthy subjects where four resistive loads were applied in a random order during the breath and 8-min recording made in each condition. The HRV spectral power components were computed from the R-R interval sequences, and the RSA amplitude and phase were computed from the sinusoid fitting the instantaneous heart rate within each breath. Adding resistive loads resulted in 1) increasing respiratory period, 2) unchanging heart rate, and 3) increasing HRV and changing RSA characteristics. HRV and RSA characteristics are linearly correlated to the respiratory period. These modifications appear to be linked to load-induced changes in the respiratory period in each individual, because HRV and RSA characteristics are similar at a respiratory period obtained either by loading or by imposed frequency breathing. The present results are discussed with regard to the importance of the breathing cycle duration in these cardiorespiratory interactions, suggesting that these interactions may depend on the time necessary for activation and dissipation of neurotransmitters involved in RSA.


Assuntos
Frequência Cardíaca/fisiologia , Coração/fisiologia , Mecânica Respiratória/fisiologia , Adulto , Resistência das Vias Respiratórias , Homeostase , Humanos , Pessoa de Meia-Idade , Análise de Regressão
8.
IEEE Trans Biomed Eng ; 46(9): 1161-5, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10493079

RESUMO

A statistical method with the advantages of 1) enabling graphical representation of within-respiratory cycle heart rate variations, 2) detecting the presence of respiratory sinus arrhythmia (RSA) in a moving window, and 3) providing breath-by-breath RSA amplitude and phase obtained from the fitting of a sinusoid to the instantaneous relative heart rate is presented.


Assuntos
Arritmia Sinusal/diagnóstico , Frequência Cardíaca/fisiologia , Modelos Estatísticos , Processamento de Sinais Assistido por Computador , Adolescente , Adulto , Apresentação de Dados , Eletrocardiografia , Humanos , Modelos Cardiovasculares , Valores de Referência , Respiração
9.
Respir Physiol ; 113(2): 167-79, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9832235

RESUMO

In order to determine changes in breathing patterns brought about by resistive loading, ventilation was recorded in 11 healthy subjects with four linear resistances (3.57, 5.75, 8.76 and 13.13 cmH2O L(-1) sec) added in a random order throughout the entire breath. At steady state, a breath-by-breath analysis of airflow was used to quantify the pattern of breathing in terms of respiratory variables: TI, TE, Tt, VT, VT/TI, TI/Tt, and by taking TI, TE, VT all together (TRIAD) and also the shape of the entire airflow profile quantified by harmonic analysis (ASTER). Group analysis using ANOVA showed significant changes in all variables. There were increasing changes with increasing loads in all variables, the smallest changes being in TI/Tt. Within to between-individual comparisons between two loads showed that only TI/Tt and the ASTER were more similar within than between-individuals for all comparisons. It was concluded that at steady state mechanisms of load compensation come into play inducing changes in the pattern of breathing proportional to the loads while maintaining some of the individual characteristics.


Assuntos
Resistência das Vias Respiratórias/fisiologia , Mecânica Respiratória/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Pressão do Ar , Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência
11.
Acta Genet Med Gemellol (Roma) ; 42(2): 171-84, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7976112

RESUMO

To better understand behavioural and genetic influences upon breathing, the breathing patterns of 8 pairs of monozygous (MZ) twins were measured under 4 behavioural conditions; relaxed without standardisation; eyes closed; eyes open; and reading. Breathing was quantified by inspiratory and expiratory durations (TI, TE), tidal volume (VT) and derived variables. Airflow shape was normalised and quantified using 8 dimensions. Reading caused breathing to increase by > 500 ml/min compared to the other four conditions. Differences in breathing between combinations of two conditions were compared by testing whether the differences within an individual were smaller than the differences between random pairs of individuals from the same 16 subjects. For almost all respiratory variables, and whatever the behavioural condition, there were highly significant similarities within an individual (p < 0.00025 on 32/80 comparisons). Under each condition, the differences within MZ twin-pairs were compared to the differences within random-pairs from the same subject population. There were highly significant similarities within twin-pairs for the airflow shape across all conditions. However, TI, TE and VT failed to consistently show significant similarities within twin pairs. Hence, an individual's airflow shape appears to be a fundamental characteristic which is conserved when behavioural condition and level of ventilation changes. Further, MZ twins have similar airflow shapes--whatever the behavioural situation. Hence, behavioural influences upon airflow shape act upon monozygous twin pairs in similar ways, or such influences were negligible under the conditions of the present study.


Assuntos
Comportamento/fisiologia , Respiração/genética , Gêmeos Monozigóticos , Adolescente , Adulto , Feminino , Fixação Ocular/fisiologia , Humanos , Masculino , Leitura , Relaxamento/fisiologia , Vigília/fisiologia
12.
Respir Physiol ; 75(2): 199-209, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2711051

RESUMO

Sixteen healthy adult subjects underwent two studies separated by 4-5 years to test whether their resting pattern of breathing was reproducible over time. From breath-by-breath analysis of airflow, measured with a pneumotachometer, the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), tidal volume (VT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the shape of the entire airflow profile was quantified by harmonic analysis (ASTER). A statistical analysis was designed to compare differences between the 1st and the 2nd recording within individuals with those differences observed between random pairs of recordings from the two studies in the same 16 individuals. It was found that all variables were significantly more similar within-individuals than between-individuals; this is best demonstrated when considering the ASTER and/or the TRIAD. It was concluded that the individuality of breathing pattern is maintained over a long period despite changes in smoking habit, weight, mild respiratory diseases, and other changes which occurred between the two studies in our subjects.


Assuntos
Respiração , Adulto , Feminino , Humanos , Individualidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Espirometria
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