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1.
Nutrients ; 13(8)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34444646

RESUMO

A poor understanding of malnutrition burden is a common reason for not prioritizing the care of small and nutritionally at-risk infants aged under-six months (infants u6m). We aimed to estimate the anthropometric deficit prevalence in infants u6m attending health centres, using the Composite Index of Anthropometric Failure (CIAF), and to assess the overlap of different individual indicators. We undertook a two-week survey of all infants u6m visiting 18 health centres in two zones of the Oromia region, Ethiopia. We measured weight, length, and MUAC (mid-upper arm circumference) and calculated weight-for-length (WLZ), length-for-age (LAZ), and weight-for-age z-scores (WAZ). Overall, 21.7% (95% CI: 19.2; 24.3) of infants u6m presented CIAF, and of these, 10.7% (95% CI: 8.93; 12.7) had multiple anthropometric deficits. Low MUAC overlapped with 47.5% (95% CI: 38.0; 57.3), 43.8% (95% CI: 34.9; 53.1), and 42.6% (95% CI: 36.3; 49.2) of the stunted, wasted, and CIAF prevalence, respectively. Underweight overlapped with 63.4% (95% CI: 53.6; 72.2), 52.7% (95% CI: 43.4; 61.7), and 59.6% (95% CI: 53.1; 65.9) of the stunted, wasted, and CIAF prevalence, respectively. Anthropometric deficits, single and multiple, are prevalent in infants attending health centres. WAZ overlaps more with other forms of anthropometric deficits than MUAC.


Assuntos
Centros Comunitários de Saúde , Transtornos da Nutrição do Lactente/epidemiologia , Antropometria , Estatura , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prevalência , Magreza
3.
Nutrients ; 13(2)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672692

RESUMO

Small and nutritionally at-risk infants under six months, defined as those with wasting, underweight, or other forms of growth failure, are at high-risk of mortality and morbidity. The World Health Organisation 2013 guidelines on severe acute malnutrition highlight the need to effectively manage this vulnerable group, but programmatic challenges are widely reported. This review aims to inform future management strategies for small and nutritionally at-risk infants under six months in low- and middle-income countries (LMICs) by synthesising evidence on existing breastfeeding support packages for all infants under six months. We searched PubMed, CINAHL, Cochrane Library, EMBASE, and Global Health databases from inception to 18 July 2018. Intervention of interest were breastfeeding support packages. Studies reporting breastfeeding practices and/or caregivers'/healthcare staffs' knowledge/skills/practices for infants under six months from LMICs were included. Study quality was assessed using NICE quality appraisal checklist for intervention studies. A narrative data synthesis using the Synthesis Without Meta-analysis (SWiM) reporting guideline was conducted and key features of successful programmes identified. Of 15,256 studies initially identified, 41 were eligible for inclusion. They were geographically diverse, representing 22 LMICs. Interventions were mainly targeted at mother-infant pairs and only 7% (n = 3) studies included at-risk infants. Studies were rated to be of good or adequate quality. Twenty studies focused on hospital-based interventions, another 20 on community-based and one study compared both. Among all interventions, breastfeeding counselling (n = 6) and education (n = 6) support packages showed the most positive effect on breastfeeding practices followed by breastfeeding training (n = 4), promotion (n = 4) and peer support (n = 3). Breastfeeding education support (n = 3) also improved caregivers' knowledge/skills/practices. Identified breastfeeding support packages can serve as "primary prevention" interventions for all infants under six months in LMICs. For at-risk infants, these packages need to be adapted and formally tested in future studies. Future work should also examine impacts of breastfeeding support on anthropometry and morbidity outcomes. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018102795).


Assuntos
Aleitamento Materno , Aconselhamento/métodos , Transtornos da Nutrição do Lactente/prevenção & controle , Mães/educação , Cuidado Pós-Natal/métodos , Adulto , Países em Desenvolvimento , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Avaliação de Programas e Projetos de Saúde , Apoio Social
4.
Nutrients ; 12(7)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32660020

RESUMO

(1) Introduction: Current evidence on managing infants under six months with growth failure or other nutrition-related risk is sparse and low quality. This review aims to inform research priorities to fill this evidence gap, focusing on breastfeeding practices. (2) Methods: We searched PubMed, CINAHL Plus, and Cochrane Library for studies on feeding interventions that aim to restore or improve the volume or quality of breastmilk and breastfeeding when breastfeeding practices are sub-optimal or prematurely stopped. We included studies from both low- and middle-income countries and high-income countries. (3) Results: Forty-seven studies met the inclusion criteria. Most were from high-income countries (n = 35, 74.5%) and included infants who were at risk of growth failure at birth (preterm infants/small for gestational age) and newborns with early growth faltering. Interventions included formula fortification or supplementation (n = 31, 66%), enteral feeds (n = 8, 17%), cup feeding (n = 2, 4.2%), and other (n = 6, 12.8%). Outcomes included anthropometric change (n = 40, 85.1%), reported feeding practices (n = 16, 34%), morbidity (n = 11, 23.4%), and mortality (n = 5, 10.6%). Of 31 studies that assessed formula fortification or supplementation, 30 reported anthropometric changes (n = 17 no effect, n = 9 positive, n = 4 mixed), seven morbidity (n = 3 no effect, n = 2 positive, n = 2 negative), five feeding (n = 2 positive, n = 2 no effect, n = 1 negative), and four mortality (n = 3 no effect, n = 1 negative). Of eight studies that assessed enteral feed interventions, seven reported anthropometric changes (n = 4 positive, n = 3 no effect), five feeding practices (n = 2 positive, n = 2 no effect, n = 1 negative), four morbidity (n = 4 no effect), and one reported mortality (n = 1 no effect). Overall, interventions with positive effects on feeding practices were cup feeding compared to bottle-feeding among preterm; nasogastric tube feed compared to bottle-feeding among low birth weight preterm; and early progressive feeding compared to delayed feeding among extremely low birth weight preterm. Bovine/cow milk feeding and high volume feeding interventions had an unfavourable effect, while electric breast pump and Galactagogue had a mixed effect. Regarding anthropometric outcomes, overall, macronutrient fortified formula, cream supplementation, and fortified human milk formula had a positive effect (weight gain) on preterm infants. Interventions comparing human breastmilk/donor milk with formula had mixed effects. Overall, only human milk compared to formula intervention had a positive effect on morbidity among preterm infants, while none of the interventions had any positive effect on mortality. Bovine/cow milk supplementation had unfavourable effects on both morbidity and mortality. (4) Conclusion: Future research should prioritise low- and middle-income countries, include infants presenting with growth failure in the post-neonatal period and record effects on morbidity and mortality outcomes.


Assuntos
Aleitamento Materno , Nutrição Enteral , Fórmulas Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Alimentação Artificial , Insuficiência de Crescimento , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Leite Humano , Ganho de Peso
5.
Indian J Dent Res ; 30(1): 112-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30900668

RESUMO

Context: The use of antioxidants immediately after bleaching showed increased bond strength. Aims: This study aimed to compare the effects of natural antioxidants on the shear bond strength of composite resin to bleached enamel. Materials and Methods: Fifty extracted single-rooted upper incisors were decoronated by sectioning the roots 2 mm below the cementoenamel junction, and then, crowns were embedded in autopolymerizing acrylic resin block (3.0 cm × 3.0 cm × 3.0 cm) with the labial surface exposed. They were randomly divided into five groups, depending on the type of antioxidant used (n = 10): (i) Group 1: control (no bleaching), (ii) Group 2: bleaching only, (iii) Group 3: bleaching + 10% sodium ascorbate (antioxidant), (iv) Group 4: bleaching + green tea, and (v) Group 5: bleaching + white tea. Labial surfaces of 40 teeth were bleached with 38% hydrogen peroxide for 20 min following manufacturer's instructions. After that, the experimental groups (Groups 3, 4, and 5) were treated with respective antioxidant solutions before composite restorations were done using a cylindrical plastic mold (3 mm × 5 mm). Shear bond strength of the specimens was tested under universal testing machine. Statistical Analysis: Data were analyzed with ANOVA and Tukey's post hoc test. Results: There were statistically significant differences between shear bond strength of control groups (Groups 1 and 2) and experimental groups (P < 0.05), but no significant difference in bond strength was observed among the antioxidants used. Conclusion: Application of antioxidants immediately after bleaching showed increased bond strength. Green tea and white tea extract can be used as alternative antioxidants in improving the bond strength of enamel.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Resinas Compostas , Colagem Dentária , Esmalte Dentário , Extratos Vegetais/farmacologia , Resistência ao Cisalhamento/efeitos dos fármacos , Chá/química , Clareamento Dental , Humanos , Peróxido de Hidrogênio , Incisivo , Maxila , Clareadores Dentários
6.
BMJ Open ; 8(6): e015919, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29991625

RESUMO

INTRODUCTION: Diabetes and hypertension are two leading non-communicable conditions, which are suboptimally managed in India. Thus, innovative comprehensive approaches that can concomitantly improve their detection, prevention and control are warranted. METHODS AND ANALYSIS: UDAY, a 5-year initiative, aims to reduce the risk of diabetes and hypertension and improve management by implementing a comprehensive intervention programme in the two selected study sites, Sonipat and Visakhapatnam (Vizag). It has a pre-post evaluation design with representative cross-sectional surveys before and after intervention. Within these two sites, urban and rural subsites each with a total population of approximately 100 000 people each were selected and a baseline and postintervention assessment was conducted deploying five surveys [among general population (including body measurements or biosamples), patients, healthcare providers including physicians and pharmacists, health facilities], which will determine the knowledge levels about diabetes and hypertension, the proportion treated and controlled; the patient knowledge and self-management skills; healthcare providers' management practices; the level of access and barriers to obtaining care.The interventions will include: tailored health promotion for improving public knowledge; screening of adults aged ≥ 30 years for identifying those at high risk of diabetes and/or hypertension for linkage to the healthcare system; patient education using technology enabled community health workers, geographic information system (GIS) based mapping of the communities, healthcare provider training on management guidelines, community based diabetes registry and; advocacy to improve access to healthcare. The baseline surveys have been completed, the study areas mapped using GIS and the interventions are being implemented. UDAY is expected to increase over baseline the levels of: public knowledge about diabetes and hypertension; those treated and controlled; patient self-management skills; the use of guideline based management by providers and; access to healthcare, leading to improved health outcomes and inform development of a India relevant chronic care model. ETHICS AND DISSEMINATION: Ethical clearance for conduct of the study was obtained from the Institutional Ethics Committee (IEC) of the Public Health Foundation of India. The findings will be targeted primarily at public health policymakers and advocates, but will be disseminated widely through other mechanisms including conference presentations and peer-reviewed publications, as well as to the participating communities.


Assuntos
Diabetes Mellitus/prevenção & controle , Equidade em Saúde/organização & administração , Promoção da Saúde/organização & administração , Hipertensão/prevenção & controle , Fortalecimento Institucional , Serviços de Saúde Comunitária , Estudos Transversais , Diabetes Mellitus/terapia , Feminino , Humanos , Hipertensão/terapia , Índia , Masculino , Medição de Risco , Autocuidado , Inquéritos e Questionários
7.
Indian J Community Med ; 43(Suppl 1): S12-S17, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30686868

RESUMO

Background: There are multiple risk factors during adolescence, which become precursors of various diseases and injuries inflicting high morbidity, mortality, and disability. There are several gaps in adolescent health research in India; one among them is that programs targeting adolescent health are constrained by the absence of rigorous interventional research informing interventions for improving adolescent health. This study aims to document the effectiveness of intervention on adolescent health and knowledge change on the risk factors among adolescents in one of the selected districts in Gujarat, India. Methods: This was an interventional study with quasi-experimental design executed in one of the blocks of Gujarat. Baseline was conducted in 2013-2014 followed by intervention and the end line during 2016-2017. A structured validated questionnaire after pilot testing was executed to collect information on sociodemographic profile, nutrition status, menstrual hygiene practices, reproductive and sexual health, substance abuse, program awareness and utilization, and empowerment through life skills of adolescents in baseline and end line survey. Data analysis was carried out using IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp). Results: This study documented increased awareness regarding anemia, knowledge about STD and HIV/AIDS, reduced addiction to tobacco, improved practices during menstrual hygiene and engagement with adolescent services/schemes in the intervention site. Conclusion: This study concludes that evidence-based interventions lead to increase in knowledge and practices; however, some improvements have also been documented in the nonintervention site. Therefore, changes due to interventions could not be attributed completely for improving adolescent health. Further long term interventional studies are required to develop a robust evidence on improving health of adolescents in India.

8.
J Clin Diagn Res ; 11(5): ZC68-ZC71, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28658911

RESUMO

INTRODUCTION: Mouth rinses have been popularly used as a supplementary oral hygiene aid. A lot of commercially available mouth rinses possess few adverse effects, which has necessitated the search for alternative and herbal mouth rinses. AIM: The aim of the study was to assess the effect of rinsing with green coffee bean extract in comparison with chlorhexidine mouthwash and sterile water on salivary Streptococcus mutans count. MATERIALS AND METHODS: A randomized parallel controlled clinical trial was planned and 45 subjects aged between 18-22 years were selected. The subjects were divided into three groups (n=15 in each group): Group A: Study group: 2% Green coffee bean extract, Group B: Positive control: 0.2% Chlorhexidine (CHX), Group C: Negative control: Sterile water. Group A subjects rinsed mouth with 5 ml of 2% Green coffee bean extract for one minute. Group B subjects rinsed mouth with 5 ml 0.2% CHX mouthwash for one minute. Group C subjects rinsed mouth with 5 ml of Sterile water for one minute twice daily for two weeks. Baseline samples (Pre rinse) were collected on day 1 and post rinsing saliva samples were collected after 14 days. The samples were cultured using Mitis Salivarius Agar enriched with Bacitracin and colonies were counted using a hand held digital colony counter. The statistical analysis was done using paired t-test, One-way variance ANOVA and Post-Hoc tests. RESULTS: The Green coffee bean extract group showed a statistical significant reduction in Streptococcus mutans colony count before and after intervention which was comparable with CHX group. CONCLUSION: Green coffee bean extract as a mouthwash can be explored as a safe and effective alternative to CHX mouthwash.

9.
Springerplus ; 5: 643, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27330909

RESUMO

INTRODUCTION: Although endometriosis with sigmoid serosal involvement is not uncommon in women of childbearing age, the mucosal and lymph node involvement is rare and differential diagnosis from colon cancer and diverticulitis may be difficult due to poor diagnostic accuracy of colonoscopy and colonic biopsies. CASE PRESENTATION: We present a case of a nulliparous woman presenting with large bowel obstruction. She underwent emergency sigmoid colectomy based on clinical and radiological findings. At operation, the pathology was thought to be primary sigmoid tumour. However, histopathological examination of the sigmoid colon led to the final diagnosis of large intestinal endometriosis. CONCLUSION: Rectosigmoid endometriosis is often difficult to diagnose but should be considered in differential diagnosis of child bearing aged women with lower gastrointestinal tract obstruction.

10.
Cutis ; 96(2): E27-30, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26367761

RESUMO

Pyogenic granuloma (PG) is a tumorlike growth of the oral mucosa or skin that is considered to be an exaggerated conditioned response to minor trauma. It usually is painless, bleeds easily, and is considered to be nonneoplastic in nature. Pyogenic granuloma predominantly occurs in the second decade of life, mostly among young adult females. Clinically, it is a smooth or lobulated exophytic lesion manifesting as small, red, erythematous papules on a pedunculated or sometimes sessile base that usually is hemorrhagic. We report the case of 30-year-old woman who presented with a PG in the anterior palatal region during pregnancy that recurred with a satellite lesion 1 year following surgical excision.


Assuntos
Granuloma Piogênico/diagnóstico , Doenças da Boca/diagnóstico , Palato/patologia , Complicações na Gravidez/diagnóstico , Adulto , Feminino , Granuloma Piogênico/patologia , Granuloma Piogênico/cirurgia , Humanos , Doenças da Boca/patologia , Doenças da Boca/cirurgia , Gravidez , Complicações na Gravidez/patologia , Complicações na Gravidez/cirurgia , Recidiva
11.
Acta Obstet Gynecol Scand ; 94(5): 542-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25737188

RESUMO

To explore the correlation between urinary protein:creatinine ratio and 24-h excretion of protein, we studied 149 women referred to a day assessment unit for investigations for suspected preeclampsia. Paired samples were obtained for measurement of urinary protein:creatinine ratio and 24-h protein excretion. Collection of a 24-h urine sample was validated by the daily creatinine excretion. The outcome measure was proteinuria of 300 mg/day or more. Inaccurate 24-h collection was observed in 17% of women. All women (n = 56) with a protein:creatinine ratio >60 mg/mM had significant proteinuria. No woman with protein:creatinine ratio <18 mg/mM (n = 20) had significant proteinuria. We recommend that a dual cut-off should be used for excluding and "ruling in" the diagnosis of significant proteinuria. A 24-h urine collection should be used only for urinary protein:creatinine ratio values between 18 and 60 mg/mM in the detection of significant proteinuria.


Assuntos
Creatinina/urina , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/urina , Proteinúria/diagnóstico , Proteinúria/urina , Adulto , Feminino , Humanos , Pré-Eclâmpsia/etiologia , Valor Preditivo dos Testes , Gravidez , Proteinúria/complicações , Curva ROC , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
12.
Cell Tissue Bank ; 15(3): 297-305, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24002077

RESUMO

As esthetics gain importance, periodontal plastic surgical procedures involving soft tissue grafts are becoming commoner both around natural teeth as well as around implants. Periodontal soft tissue grafts are primarily used for the purpose of root coverage and in pre-prosthetic surgery to thicken a gingival site or to improve the crestal volume. Soft tissue grafts are usually harvested from the palate. Periodontal plastic surgical procedures involving soft tissue grafts harvested from the palate have two surgical sites; a recipient site and another donor site. Many patients are apprehensive about the soft tissue graft procedures, especially the creation of the second/donor surgical site in the palate. In the past decade, newer techniques and products have emerged which provide an option for the periodontist/patient to avoid the second surgical site. MucoMatrixX, Alloderm(®), Platelet rich fibrin, Puros(®) Dermis and Mucograft(®) are the various options available to the practicing periodontist to avoid the second surgical site. Use of these soft tissue allografts in an apprehensive patient would decrease patient morbidity and increase patient's acceptance towards periodontal plastic surgical procedures.


Assuntos
Aloenxertos/cirurgia , Implantes Dentários , Gengivoplastia , Procedimentos Cirúrgicos Reconstrutivos , Raiz Dentária/cirurgia , Animais , Colágeno/uso terapêutico , Gengivoplastia/métodos , Humanos , Procedimentos Cirúrgicos Reconstrutivos/métodos
14.
J Food Sci Technol ; 50(6): 1212-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24426037

RESUMO

Iodine Deficiency Disorders (IDD) is a public health problem in India. It is because of poor iodine availability to the body either due to loss of iodine from iodized salt or due to cooking. Since there is lack of scientific evidence on loss of iodine during different cooking methods, present study was undertaken to study the effect of different cooking methods on iodine losses. Methods used were boiling, roasting, shallow frying, deep frying, pressure cooking and microwave cooking. The loss of iodine ranged from 6.58% to 51.08%. Minimum losses were found during shallow frying where cooking time of salt was 1 min and 15 s and maximum during pressure cooking where cooking time of salt was 26 min. Losses during boiling, roasting, deep frying and microwave cooking were found to be 40.23%, 10.57%, 10.40% and 27.13% respectively. From the obtained results, authors have concluded that the loss of iodine depends upon type of cooking method and time of addition of salt during cooking.

15.
Contemp Clin Dent ; 4(4): 556-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24403810

RESUMO

Ideal alveolar ridge width and height allows placement of a natural appearing pontic, which provides maintenance of a plaque-free environment. The contour of a partially edentulous ridge should be thoroughly evaluated before a fixed partial denture is undertaken. Localized alveolar ridge defect refers to a volumetric deficit of the limited extent of bone and soft-tissue within the alveolar process. These ridge defects can be corrected by hard tissue and/or soft-tissue augmentation. A 30-year-old male patient was referred to the Department of Periodontology for correction of Seibert's Class III ridge defect in the lower anterior region. Granulation tissue/connective tissue present at the base of the defect was removed after elevation of full thickness flap. MucoMatrixX, an animal derived, collagen based soft-tissue graft was sutured to the labial flap and bone graft was placed into the defect. If a soft-tissue graft material could be used to replace the palatal grafts, then all the possible complications associated with donor site would be eliminated and above all periodontal plastic surgery and ridge augmentation would be better accepted by patients.

16.
Drug Metab Dispos ; 41(2): 398-405, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23160820

RESUMO

The pregnane X receptor (PXR, NR1I2) plays a pivotal role in the disposition and detoxification of numerous foreign and endogenous chemicals by increasing transcription of numerous target genes, including phase I and II drug-metabolizing enzymes and transporters. In the present study, yeast two-hybrid screening identified an E3 ubiquitin ligase, RBCK1 (Ring-B-box-coiled-coil protein interacting with protein kinase C-1), as a human pregnane X receptor (hPXR)-interacting protein. Coimmunoprecipitation studies confirmed the interaction between RBCK1 and hPXR when both were ectopically expressed in AD-293 cells. Domain mapping studies showed that the interaction between RBCK1 and hPXR involves all RBCK1 domains. We further demonstrate that RBCK1 ubiquitinates hPXR, and this may target hPXR for degradation by the ubiquitin-proteasome pathway. Simultaneous ectopic overexpression of RBCK1 and PXR decreased PXR levels in AD-293 cells, and this decrease was inhibited by the proteasomal inhibitor MG-132 (carbobenzoxy-Leu-Leu-leucinal). Furthermore, overexpression of RBCK1 decreased endogenous levels of PXR in HepG2 cells. Of importance, ectopic overexpression and silencing of endogenous RBCK1 in primary human hepatocytes resulted in a decrease and increase, respectively, in endogenous PXR protein levels and in the induction of PXR target genes by rifampicin. These results suggest that RBCK1 is important for the ubiquitination of PXR and may play a role in its proteasomal degradation.


Assuntos
Hepatócitos/enzimologia , Receptores de Esteroides/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Imunoprecipitação , Leupeptinas/farmacologia , Receptor de Pregnano X , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Interferência de RNA , Receptores de Esteroides/genética , Fatores de Transcrição/genética , Transfecção , Técnicas do Sistema de Duplo-Híbrido , Ubiquitina-Proteína Ligases , Ubiquitinação
17.
Free Radic Biol Med ; 52(9): 1666-79, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22343416

RESUMO

While some studies show that carbon tetrachloride-mediated metabolic oxidative stress exacerbates steatohepatitic-like lesions in obese mice, the redox mechanisms that trigger the innate immune system and accentuate the inflammatory cascade remain unclear. Here we have explored the role of the purinergic receptor P2X7-NADPH oxidase axis as a primary event in recognizing the heightened release of extracellular ATP from CCl(4)-treated hepatocytes and generating redox-mediated Kupffer cell activation in obese mice. We found that an underlying condition of obesity led to the formation of protein radicals and posttranslational nitration, primarily in Kupffer cells, at 24h post-CCl(4) administration. The free radical-mediated oxidation of cellular macromolecules, which was NADPH oxidase and P2X7 receptor-dependent, correlated well with the release of TNF-α and MCP-2 from Kupffer cells. The Kupffer cells in CCl(4)-treated mice exhibited increased expression of MHC Class II proteins and showed an activated phenotype. Increased expression of MHC Class II was inhibited by the NADPH oxidase inhibitor apocynin , P2X7 receptor antagonist A438709 hydrochloride, and genetic deletions of the NADPH oxidase p47 phox subunit or the P2X7 receptor. The P2X7 receptor acted upstream of NADPH oxidase activation by up-regulating the expression of the p47 phox subunit and p47 phox binding to the membrane subunit, gp91 phox. We conclude that the P2X7 receptor is a primary mediator of oxidative stress-induced exacerbation of inflammatory liver injury in obese mice via NADPH oxidase-dependent mechanisms.


Assuntos
Tetracloreto de Carbono/toxicidade , Fígado Gorduroso/metabolismo , Macrófagos do Fígado/metabolismo , NADPH Oxidases/metabolismo , Obesidade/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Animais , Técnicas de Cocultura , Fígado Gorduroso/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Estresse Oxidativo , Reação em Cadeia da Polimerase em Tempo Real
19.
Pharmacol Res ; 63(5): 405-13, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21292004

RESUMO

CYP2Cs and CYP3A4 sub families of enzymes of the Cytochrome P450 super family metabolize clinically prescribed therapeutics. Constitutive and induced expressions of these enzymes are under the control of HNF4α and rifampicin activated PXR. In the present study, we show a mechanism for ligand dependent synergistic cross talk between PXR and HNF4α. Two-hybrid screening identified NCOA6 as a HNF4α interacting protein. NCOA6 was also found to interact with PXR through the first LXXLL motif in GST pull down and mammalian two hybrid assays. NCOA6 enhances the synergistic activation of CYP2C9 and CYP3A4 promoter activity by PXR and HNF4α in the presence of rifampicin. However silencing NCOA6 abrogated the synergistic activation and induction of CYP2C9 by PXR-HNF4α but not of CYP3A4. ChIP analysis revealed that NCOA6 could bridge HNF4α and PXR binding sites of the CYP2C9 promoter. Our results indicate that NCOA6 is responsible for the synergistic activation of CYP2C9 by HNF4α and PXR and NCOA6 differentially regulates CYP2C9 and CYP3A4 gene expression though both the genes are regulated by the same nuclear receptors.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP3A/genética , Regulação Enzimológica da Expressão Gênica , Coativadores de Receptor Nuclear/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Imunoprecipitação da Cromatina , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP3A/metabolismo , Células Hep G2 , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Coativadores de Receptor Nuclear/metabolismo , Receptor de Pregnano X , Mapeamento de Interação de Proteínas , Receptores de Esteroides/metabolismo , Técnicas do Sistema de Duplo-Híbrido
20.
Mol Cell Biol ; 31(3): 466-81, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21135126

RESUMO

Hepatocyte nuclear factor 4α (HNF4α) controls the expression of many critical metabolic pathways, and the Mediator complex occupies a central role in recruiting RNA polymerase II (Pol II) to these gene promoters. An impaired transcriptional HNF4α network in human liver is responsible for many pathological conditions, such as altered drug metabolism, fatty liver, and diabetes. Here, we report that Med25, an associated member of the Mediator complex, is required for the association of HNF4α with Mediator, its several cofactors, and RNA Pol II. Further, increases and decreases in endogenous Med25 levels are reflected in the composition of the transcriptional complex, Pol II recruitment, and the expression of HNF4α-bound target genes. A novel feature of Med25 is that it imparts "selectivity." Med25 affects only a significant subset of HNF4α target genes that selectively regulate drug and lipid metabolism. These results define a role for Med25 and the Mediator complex in the regulation of xenobiotic metabolism and lipid homeostasis.


Assuntos
Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Complexo Mediador/metabolismo , Regiões Promotoras Genéticas , RNA Polimerase II/metabolismo , Xenobióticos/metabolismo , Células Cultivadas , Sistema Enzimático do Citocromo P-450/metabolismo , Regulação para Baixo/genética , Inativação Gênica , Células HEK293 , Células Hep G2 , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Fígado/enzimologia , Preparações Farmacêuticas/metabolismo , Ligação Proteica , Transdução de Sinais , Transcrição Genética
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