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OBJECTIVES: Despite robust evidence on health inequalities in adulthood, less attention has been paid to inequalities in adolescence. The aim of this overview was to examine systematic review (SR) evidence on the equity impact of population-level interventions intended to improve health, happiness and wellbeing for adolescents. STUDY DESIGN: An overview (review of systematic reviews). METHODS: Eleven electronic databases were systematically searched to identify SRs of population-level interventions for adolescent health. A secondary data analysis of socioeconomic inequality was conducted to identify whether SRs reported on primary studies in terms of disadvantage, by measures of socioeconomic status (SES) and by differential effects. RESULTS: 35,310 review titles were screened; 566 full texts were retrieved and 140 SRs met the predefined selection criteria. Differential intervention effects were considered in 42/140 (30%) SRs, 18/140 (13%) reported primary studies using an SES measure and 16/140 (11%) explicitly reported differential effects. 15/140 SRs (11%) explicitly focused on socioeconomic inequalities; of these 4/15 reported differential intervention effects in more detail, 7/15 concluded there was insufficient primary evidence to identify the impact of interventions on socioeconomic inequalities and 4/15 planned to examine differential effects by SES, but this was not reported further. CONCLUSIONS: Our overview identifies that there is limited SR evidence on the equity impact of population-level interventions for adolescent health. Strengthening the evidence on whether interventions narrow or widen inequalities for adolescents must be a priority for public health research.
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Saúde do Adolescente , Equidade em Saúde , Promoção da Saúde , Adolescente , Disparidades nos Níveis de Saúde , Humanos , Avaliação de Programas e Projetos de Saúde , Fatores Socioeconômicos , Revisões Sistemáticas como AssuntoRESUMO
OBJECTIVE: Pilot trial to compare prism therapy and visual search training, for homonymous hemianopia, to standard care (information only). METHODS: Prospective, multicentre, parallel, single-blind, three-arm RCT across fifteen UK acute stroke units. PARTICIPANTS: Stroke survivors with homonymous hemianopia. INTERVENTIONS: Arm a (Fresnel prisms) for minimum 2 hours, 5 days per week over 6 weeks. Arm b (visual search training) for minimum 30 minutes, 5 days per week over 6 weeks. Arm c (standard care-information only). INCLUSION CRITERIA: Adult stroke survivors (>18 years), stable hemianopia, visual acuity better than 0.5 logMAR, refractive error within ±5 dioptres, ability to read/understand English and provide consent. OUTCOMES: Primary outcomes were change in visual field area from baseline to 26 weeks and calculation of sample size for a definitive trial. Secondary measures included Rivermead Mobility Index, Visual Function Questionnaire 25/10, Nottingham Extended Activities of Daily Living, Euro Qual, Short Form-12 questionnaires and Radner reading ability. Measures were post-randomization at baseline and 6, 12 and 26 weeks. RANDOMIZATION: Randomization block lists stratified by site and partial/complete hemianopia. BLINDING: Allocations disclosed to patients. Primary outcome assessor blind to treatment allocation. RESULTS: Eighty-seven patients were recruited: 27-Fresnel prisms, 30-visual search training and 30-standard care; 69% male; mean age 69 years (SD 12). At 26 weeks, full results for 24, 24 and 22 patients, respectively, were compared to baseline. Sample size calculation for a definitive trial determined as 269 participants per arm for a 200 degree2 visual field area change at 90% power. Non-significant relative change in area of visual field was 5%, 8% and 3.5%, respectively, for the three groups. Visual Function Questionnaire responses improved significantly from baseline to 26 weeks with visual search training (60 [SD 19] to 68.4 [SD 20]) compared to Fresnel prisms (68.5 [SD 16.4] to 68.2 [18.4]: 7% difference) and standard care (63.7 [SD 19.4] to 59.8 [SD 22.7]: 10% difference), P=.05. Related adverse events were common with Fresnel prisms (69.2%; typically headaches). CONCLUSIONS: No significant change occurred for area of visual field area across arms over follow-up. Visual search training had significant improvement in vision-related quality of life. Prism therapy produced adverse events in 69%. Visual search training results warrant further investigation.
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Atividades Cotidianas , Óculos , Hemianopsia/reabilitação , Qualidade de Vida , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemianopsia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Método Simples-Cego , Inquéritos e Questionários , Resultado do Tratamento , Acuidade Visual/fisiologia , Campos Visuais/fisiologiaRESUMO
Background: This is the first research to examine how the policy of patient choice and commercial contracting where NHS funds are given to private providers to tackle waiting times, impacted on direct NHS provision and treatment inequalities. Methods: An ecological study of NHS funded elective primary hip arthroplasties in Scotland using routinely collected inpatient data 1 April 1993-31 March 2013. Results: An increased use of private sector provision by NHS Boards was associated with a significant decrease in direct NHS provision in 2008/09 (P < 0.01) and with widening inequalities by age and socio-economic deprivation. National treatment rate fell from 143.8 (140.3, 147.3) per 100 000 in 2006/07 to 137.8 (134.4, 141.2) per 100 000 in 2007/08. By 2012/13, territorial NHS Boards had not recovered 2006/07 levels of provision; this was most marked for NHS Boards with the greatest use of private sector, namely Fife, Grampian and Lothian. Patients aged 85 years and over or living in the more deprived areas of Scotland appear to have been disadvantaged since the onset of patient choice in 2002. Conclusions: NHS funding of private sector provision for elective hip arthroplasty was associated with a decrease in public provision and may have contributed to an increase in age and socio-economic inequalities in treatment rates.
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Artroplastia de Quadril/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Preferência do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/psicologia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Setor Privado/estatística & dados numéricos , Privatização/organização & administração , Privatização/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Escócia , Medicina Estatal/organização & administração , Medicina Estatal/estatística & dados numéricos , Listas de EsperaRESUMO
AIMS: To determine if children and young people aged < 23 years with Type 1 diabetes differ in academic ability from age-matched control subjects without Type 1 diabetes and whether academic scores are related to glycaemic control. METHODS: Using a cross-sectional study design, we administered cognitive and academic tests (Woodcock-Johnson III Spatial Relations, General Information, Letter-Word Recognition, Calculation and Spelling tests) to young people with Type 1 diabetes (n=61) and control subjects (n=26) aged 9-22 years. The groups did not differ in age or gender. Participants with Type 1 diabetes had a disease duration of 5-17.7 years. History of glycaemic control (HbA1c , diabetic ketoacidosis and severe hypoglycaemic episodes) was obtained via medical records and interviews. RESULTS: The participants with Type 1 diabetes had a lower mean estimated verbal intelligence (IQ) level compared with those in the control group (P=0.04). Greater exposure to hyperglycaemia over time was associated with lower spelling abilities within the group with Type 1 diabetes (P=0.048), even after controlling for age, gender, socio-economic status, blood glucose level at time of testing and verbal IQ (P=0.01). History of severe hypoglycaemia or ketoacidosis was not associated with differences in academic abilities. CONCLUSIONS: In children and young people, Type 1 diabetes was associated with a lower verbal IQ. Moreover, increased exposure to hyperglycaemia was associated with lower spelling performance. These results imply that hyperglycaemia can affect cognitive function and/or learning processes that may affect academic achievement.
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Transtornos Cognitivos/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Escolaridade , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Deficiências da Aprendizagem/prevenção & controle , Adolescente , Desenvolvimento do Adolescente/efeitos dos fármacos , Adulto , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Transtornos Cognitivos/complicações , Transtornos Cognitivos/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Inteligência/efeitos dos fármacos , Deficiências da Aprendizagem/complicações , Deficiências da Aprendizagem/epidemiologia , Masculino , Missouri/epidemiologia , Risco , Adulto JovemRESUMO
OBJECTIVES: To audit national drug registers (NDRs) in Kenya, United Republic of Tanzania and Uganda with respect to national Essential Medicine Lists (EMLs) and to conduct an analysis of highly registered products including a sub-analysis of highly registered antimicrobial products. DESIGN: Retrospective analysis of registration of essential medicines and medicinal products on NDRs as of February 2018. SETTING: Not applicable. PARTICIPANTS: None. MAIN OUTCOME MEASURES: Registration status of essential medicines by country, essential medicine status of registered products by country and medicines with more than 50 registrations across all three countries. RESULTS: A high proportion of essential medicines are not registered: Kenya 28% (175/632), United Republic of Tanzania 50% (400/797) and Uganda 40% (266/663). Of registered products on the NDRs, more than half are not essential: Kenya 71% (4350/6151), United Republic of Tanzania 64% (2278/3590) and Uganda 58% (2268/3896). When the three NDRs were combined, there were 42 medicines with over 50 registered products, accounting for 30% (4153/13637) of products, many of which were non-essential. CONCLUSIONS: Non-registration of essential medicines is a barrier to availability. Over-registration of medicines, particularly non-essential medicines, diverts regulatory resources towards registering non-priority and, sometimes, clinically sub-optimal medicines. The East African Community Medicines Registration Harmonization Project has the potential to improve access to key medicines if registration of essential medicines is prioritised and registration of non-essential medicines is restricted.
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Medicamentos Essenciais , Humanos , Quênia , Uganda , Tanzânia , Estudos RetrospectivosRESUMO
Objectives: To critically appraise the quality of the studies underpinning the Global Burden of Disease (GBD) 2017 estimates for Major Depressive Disorder (MDD) with respect to i) the GBD 2017 inclusion criteria and ii) population coverage. Design: Systematic critical appraisal. Setting: Not applicable. Participants: Not applicable. Main outcome measures: Each study was critically appraised with respect to the four GBD 2017 inclusion criteria: representativeness, study method and sample, diagnostic criteria and publication from 1980 onwards. Population coverage was calculated. Results: Less than half of studies (221/467, 47.3%) were nationally representative. Only 262/467 (56.1%) of studies reported specifically on MDD and more than a third did not use DSM or ICD diagnostic criteria: 94/467 (20.1%) did not specify any diagnostic criteria and 68/467 (14.6%) relied on self-reported depression for diagnosis. Only 62/467 (13.3%) of studies were conducted during the period 2011-2017. Only 107/195 (54.9%) of countries had one or more prevalence studies. Conclusions: GBD 2017 estimates for MDD are based on incomplete country and population coverage. The inclusion of studies with non-representative populations, that do not use diagnostic criteria and the lack of specific data on MDD reduces the reliability of estimates and limits their value for policy making.
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The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs. 41%) and faster second phase (27% vs. 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles=3.24, 95% CI=0.98-10.66, p-trend=0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals.
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Dano ao DNA , Neoplasias Induzidas por Radiação/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Idoso , Biópsia , Ensaio Cometa , Reparo do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/patologia , Fenótipo , Projetos Piloto , Próstata/patologia , Próstata/efeitos da radiação , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Infantile hemangiomas are common lesions in the pediatric population; in rare cases, an infantile hemangioma can be detected along the neural axis. The purposes of our study included determination of the incidence, location, and imaging appearance of neuroaxial infantile hemangiomas and their syndromic association. We also assessed additional features of cerebral and cardiovascular anomalies that may be associated with neuroaxial lesions. MATERIALS AND METHODS: A retrospective cohort study was performed, searching the radiology database for patients with segmental infantile hemangiomas referred for assessment of possible hemangioma syndromes. We retrospectively reviewed brain and spine MR imaging studies, with particular attention paid to neuroaxial vascular lesions, as well as the relevant clinical data. Neuroaxial hemangioma imaging findings were described, and comparison of segmental cutaneous infantile hemangioma location with the imaging findings was performed in patients with confirmed hemangioma syndromes and in patients with isolated skin infantile hemangioma. RESULTS: Ninety-five patients with segmental infantile hemangioma were included in the study, 42 of whom had a hemangioma syndrome; of those, 41 had posterior fossa brain malformations, hemangioma, arterial lesions, cardiac abnormalities, and eye abnormalities (PHACE) syndrome and 1 had diffuse neonatal hemangiomatosis. Neuroaxial involvement was detected in 20/42 patients (48%) with hemangioma syndromes and in no subjects with isolated segmental infantile hemangioma (P < .001). The most common intracranial hemangioma location was within the ipsilateral internal auditory canal (83%). CONCLUSIONS: Many pediatric patients with segmental infantile hemangioma in the setting of hemangioma syndromes, especially those with PHACE, had neuroaxial hemangiomas. This finding may potentially lead to requiring additional clinical evaluation and management of these patients.
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Anormalidades do Olho , Hemangioma , Síndromes Neurocutâneas , Neoplasias Cutâneas , Criança , Hemangioma/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Síndromes Neurocutâneas/diagnóstico por imagem , Estudos Retrospectivos , SíndromeRESUMO
We have previously shown that in vitro culture of rat natural killer (NK) cells in high concentrations of recombinant interleukin 2 (rIL-2) leads to the expression of a surface glycoprotein with a molecular mass of approximately 42 kD. This glycoprotein, gp42, is not induced on other lymphocytes and thus provides a lineage-specific marker for rIL-2-activated NK cells. We here present the nucleotide sequence for gp42 cDNA. The open reading frame encodes 233 amino acids with three potential sites for N-linked glycosylation. The deduced amino acid sequence lacks an apparent transmembrane domain and instead contains a hydrophobic COOH terminus that is characteristic of glycosylphosphatidylinositol (GPI)-anchored surface proteins. Consistent with this, gp42 is cleaved from the NK-like cell line, RNK-16, by phosphatidylinositol-specific phospholipase C (PI-PLC), as is gp42 expressed on CHO cells that have been transformed with gp42 cDNA. On rIL-2-activated NK cells, gp42 is resistant to PI-PLC, though our studies suggest that gp42 on these cells is still expressed as a GPI-anchored molecule. Antibody to gp42 stimulates in RNK-16 cells an increase in inositol phosphates and in intracellular calciu, signals that are associated with the activation of lymphocytes, including NK cells. rIL-2-activated NK cells, however, lack this response to gp42 as well as to other stimuli. Thus, gp42, the only NK-specific activation antigen, is a GPI-anchored surface molecule with the capacity to stimulate transmembrane signaling.
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Interleucina-2/fisiologia , Células Matadoras Naturais/imunologia , Glicoproteínas de Membrana/genética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Sequência de Bases , Cálcio/metabolismo , Células Cultivadas , Clonagem Molecular , Glicolipídeos/fisiologia , Glicosilfosfatidilinositóis , Glicoproteínas de Membrana/imunologia , Dados de Sequência Molecular , Fosfatidilinositol Diacilglicerol-Liase , Fosfatidilinositóis/metabolismo , Fosfatidilinositóis/fisiologia , Fosfoinositídeo Fosfolipase C , Diester Fosfórico Hidrolases , Ratos , Transdução de Sinais/imunologia , TransfecçãoRESUMO
OBJECTIVES: The measurement of access to health care in the National Health Service is dominated by waiting list and waiting time targets which depend on the collection and publication of a range of government statistics. The aim of this study was to describe the purposes for which waiting statistics are collected, and the different methods of data collection in the countries of Britain, in order to assess the extent to which published data meet their objectives. STUDY DESIGN: Systematic review. METHODS: A systematic evaluation of waiting statistics in England, Scotland and Wales based on official published data collections in each country, plus a review of the relevant literature. RESULTS: Waiting statistics are collected for a number of purposes, but are primarily for performance monitoring against waiting time targets and for local planning. One method of data collection may not best serve all objectives, and there are differences in the practices of the countries of Britain. An important purpose should be to measure access to health care according to individual patient need, and limitations in the statistics were identified in this respect due to methodological issues, omissions and exclusions, hidden waits, the emphasis on achieving targets, and interpretation. CONCLUSIONS: Although there are merits in maintaining the existing series, the use of waiting statistics as the primary method of measuring and monitoring access to services has limitations, not least because statistics do not contain the information required to assess whether time waited is appropriate to need.
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Medicina Estatal , Listas de Espera , Acessibilidade aos Serviços de Saúde , Humanos , Fatores de Tempo , Reino UnidoRESUMO
Cutaneous bronchogenic cyst remains a very rare cause of a midline swelling in children. The authors report a case of a 14-month-old boy who presented with a sternal sinus and consequent abscess. Histopathological analysis revealed this to be a cutaneous bronchogenic cyst. This is a very rare lesion with only 65 cases reported in the literature. It is caused by an abnormal development in the distal tracheobronchial tree, and diagnosis is confirmed by ciliated and mucin-producing pseudostratified columnar epithelium of respiratory type on histopathological analysis. It is managed by resection of the cyst, as these cysts are often foci for subsequent infections and malignant potential has been reported.
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Cisto Broncogênico/diagnóstico , Dermatopatias/diagnóstico , Cisto Broncogênico/cirurgia , Diagnóstico Diferencial , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Dermatopatias/cirurgia , Parede TorácicaRESUMO
Sodium-phosphate cotransport in the PTH-responsive opossum kidney (OK) cell line is inhibited by PTH, cAMP, and activators of protein kinase C. In order to probe the role of cAMP, we stably transfected OK cells with an expression vector for a cAMP-binding mutation of the murine protein kinase A regulatory subunit. Two-dimensional electrophoresis of cAMP-binding proteins from transfected cells indicated a 20-fold overexpression of the mutant regulatory unit. Protein kinase A from these cells had a 20-fold increase in the concentration of cAMP required for half-maximal activation, 2.8 microM vs. 0.15 microM for wild type cells. In the transfected cells, Na-phosphate cotransport was insensitive to up to 1 mM 8-Br-cAMP and 1 microM PTH, while these same agonists caused a significant inhibition of transport in the wild type cells. The effects on Na-phosphate cotransport of the protein kinase C activators oleoyl-acetyl glycerol and tetradecanoyl-phorbol acetate, which were marked in the wild type cells, were still present, although attenuated, in the transfected mutants. With prolonged passage, the cAMP-insensitive phenotype reverted to wild type cAMP sensitivity despite continued selection for the cotransfected neo marker. The revertant cells had a normal cAMP requirement for half-maximal activation of protein kinase A, 0.13 microM, and the PTH and cAMP-sensitive inhibition of Na-phosphate cotransport was restored. We suggest that an intact and normally cAMP-sensitive protein kinase A pathway is an absolute requirement for PTH inhibition of Na-phosphate cotransport in the OK cell.
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Proteínas de Transporte/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Rim/metabolismo , Hormônio Paratireóideo/farmacologia , Fosfatos/metabolismo , Proteínas Quinases/metabolismo , Sódio/metabolismo , Simportadores , Animais , Transporte Biológico , Proteínas de Transporte/genética , Linhagem Celular , AMP Cíclico/metabolismo , Rim/citologia , Camundongos , Mutação , Gambás , Fenótipo , Proteínas Quinases/genética , Proteínas Cotransportadoras de Sódio-Fosfato , TransfecçãoRESUMO
The development of progressive glomerulosclerosis in the renal ablation model has been ascribed to a number of humoral and hemodynamic events, including the peptide growth factor, transforming growth factor-beta 1 (TGF-beta 1). An important role has also been attributed to angiotensin II (AII), which, in addition to its hemodynamic effects, can stimulate transcription of TGF-beta 1. We postulated that increased glomerular production of AII, resulting from enhanced intrinsic angiotensinogen expression, stimulates local TGF-beta 1 synthesis, activating glomerular matrix protein synthesis, and leads to sclerosis. Using in situ reverse transcription, the glomerular cell sites of alpha-1 (IV) collagen, fibronectin, laminin B1, angiotensinogen, and TGF-beta 1 mRNA synthesis were determined at sequential periods following renal ablation. The early hypertrophic phase was associated with global, but transient, increases in the mRNA for alpha-1 (IV) collagen. No changes were noted for fibronectin, TGF-beta 1, and angiotensinogen mRNAs. At 24 d after ablation, at which time sclerosis is not evident, endothelial cells, particularly in the dilated capillaries at the vascular pole, expressed angiotensinogen and TGF-beta 1 mRNAs, as well as fibronectin and laminin B1 RNA transcripts. By 74 d after ablation angiotensinogen and TGF-beta 1 mRNAs were widely distributed among endothelial and mesangial cells, and were particularly prominent in regions of evolving sclerosis. These same regions were also notable for enhanced expression of matrix protein mRNAs, particularly fibronectin. All receptor blockade inhibited angiotensinogen, TGF-beta 1, fibronectin, and laminin B1 mRNA expression by the endothelium. We conclude that, as a result of hemodynamic changes, injured or activated endothelium synthesizes angiotensinogen, triggering a cascade of TGF-beta 1 and matrix protein gene expression with resultant development of the segmental glomerular sclerotic lesion.
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Angiotensina II/fisiologia , Endotélio Vascular/lesões , Proteínas da Matriz Extracelular/biossíntese , Glomerulosclerose Segmentar e Focal/fisiopatologia , Fator de Crescimento Transformador beta/biossíntese , Angiotensina II/biossíntese , Angiotensina II/genética , Animais , Sequência de Bases , Progressão da Doença , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica , Glomerulosclerose Segmentar e Focal/etiologia , Hipertrofia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Dados de Sequência Molecular , Nefrectomia/efeitos adversos , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Circulação Renal , Fator de Crescimento Transformador beta/genéticaRESUMO
To examine the role of cytokines in mediating the lipogenic effects of endotoxin (LPS), we studied the effects of LPS and cytokines on hepatic fatty acid synthesis in LPS-sensitive C3H/OuJ mice and in LPS-resistant C3H/HeJ mice, whose macrophages are defective in the ability to produce tumor necrosis factor (TNF) and IL-1 in response to LPS. HeJ mice were 16-fold less sensitive than OuJ mice to the lipogenic effect of LPS. In OuJ mice, 10 micrograms of LPS caused a maximal increase in hepatic lipogenesis (3.86 +/- 0.41-fold), whereas in HeJ mice the maximal increase was only 1.79 +/- 0.32-fold after 100 micrograms of LPS. This lipogenic response paralleled the decreased ability of LPS to increase hepatic and splenic levels of mRNAs for TNF and IL-1 and serum levels of TNF in HeJ mice. In contrast, the maximal effect of TNF on lipogenesis was greater and the sensitivity to TNF was increased 2.4-fold in HeJ mice compared to OuJ mice. Administration of IFN-gamma before LPS in HeJ mice had no effect on IL-1 mRNA, but partially restored the LPS-induced increase in hepatic and splenic mRNA for TNF and serum TNF levels, which may account for the partial restoration of sensitivity to the lipogenic effect of LPS after IFN-gamma treatment. These results indicate that cytokines produced by mononuclear leukocytes mediate the lipogenic effects of LPS.
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Endotoxinas/farmacologia , Interferon gama/farmacologia , Monocinas/fisiologia , Animais , Ácidos Graxos/biossíntese , Expressão Gênica , Interleucina-1/genética , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C3H , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The role of the glomerular visceral epithelial cell in the physiologic turnover and pathologic breakdown of the glomerular extracellular matrix has remained largely unexplored. In this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form. In addition, the protein was heavily glycosylated and demonstrated proteolytic activity against Type I gelatin, Type IV collagen gelatin, and fibronectin. The similarity in molecular mass and substrate specificities to the 92-kD human matrix metalloproteinase-9 (MMP-9, or gelatinase B) suggested the identity of this activity, which was confirmed by immunoprecipitation and Northern blot analysis. The differences in molecular mass (98 vs. 92 kD) were not due to species-specific differences in glycosylation patterns, since cultured rat peritoneal macrophages secreted MMP-9 as a 92-kD enzyme. Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product. Using a specific monoclonal anti-MMP-9 antibody and in situ reverse transcription (ISRT) analysis of MMP-9 mRNA, the expression of this enzyme was evaluated in vivo. Normal rat glomeruli expressed little immunohistochemical or ISRT staining for MMP-9, while in rats with passive Heymann nephritis there was a major increase in MMP-9 protein and mRNA staining within the visceral epithelial cells. The temporal patterns of MMP-9 expression correlated with the period of proteinuria associated with this model, suggesting that a causal relationship may exist between GEC MMP-9 expression and changes in glomerular capillary permeability.
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Colagenases/metabolismo , Glomerulonefrite/enzimologia , Glomérulos Renais/enzimologia , Animais , Células Cultivadas , Epitélio/enzimologia , Proteínas da Matriz Extracelular/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Expressão Gênica , Hibridização In Situ , Metaloproteinase 9 da Matriz , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética , RatosRESUMO
BACKGROUND: There are a number of different approaches to physiotherapy treatment following stroke that, broadly speaking, are based on neurophysiological, motor learning and orthopaedic principles. Some physiotherapists base their treatment on a single approach, while others use a mixture of components from a number of different approaches. OBJECTIVES: To determine if there is a difference in the recovery of postural control and lower limb function in patients with stroke if physiotherapy treatment is based on orthopaedic or neurophysiological or motor learning principles, or on a mixture of these treatment principles. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched May 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of physiotherapy treatment approaches aimed at promoting the recovery of postural control and lower limb function in adult participants with a clinical diagnosis of stroke. Outcomes included measures of disability, motor impairment or participation. DATA COLLECTION AND ANALYSIS: Two review authors independently categorised the identified trials according to the inclusion and exclusion criteria, documented their methodological quality, and extracted the data. MAIN RESULTS: Twenty-one trials were included in the review, five of which were included in two comparisons. Eight trials compared a neurophysiological approach with another approach; eight compared a motor learning approach with another approach; and eight compared a mixed approach with another approach. A mixed approach was significantly more effective than no treatment or placebo control for improving functional independence (standardised mean difference (SMD) 0.94, 95% confidence intervals (CI) 0.08 to 1.80). There was no significant evidence that any single approach had a better outcome than any other single approach or no treatment control. AUTHORS' CONCLUSIONS: There is evidence that physiotherapy intervention, using a mix of components from different approaches, is significantly more effective than no treatment or placebo control in the recovery of functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy approach is more effective in promoting recovery of lower limb function or postural control following stroke than any other approach. We recommend that future research should concentrate on investigating the effectiveness of clearly described individual techniques and task-specific treatments, regardless of their historical or philsophical origin.
Assuntos
Biorretroalimentação Psicológica/métodos , Postura , Reabilitação do Acidente Vascular Cerebral , Adulto , Humanos , Perna (Membro)/fisiologia , Destreza Motora , Modalidades de Fisioterapia , Propriocepção/fisiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Electrostimulation might improve motor recovery after stroke by providing neuromuscular re-training. OBJECTIVES: To find if electrostimulation improved functional motor ability, and the ability to undertake activities of daily living. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), CINAHL (1982 to January 2004), AMED - Allied and Complementary Medicine Database (1985 to January 2004), Physiotherapy Evidence Database (PEDro), REHABDATA and the ISI Science Citation Index (1981 to 2003). We placed a request on the PHYSIO e-mail discussion list and contacted authors of relevant studies to elicit any unpublished or ongoing studies, searched the reference lists of included trials and contacted trialists. SELECTION CRITERIA: Randomised controlled trials of electrostimulation delivered to the peripheral neuromuscular system which was designed to improve voluntary movement control, functional motor ability and activities of daily living. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Of the 2077 references identified, 24 trials were included in this review. For electrostimulation compared with no treatment this review found that electrostimulation improved some aspects of functional motor ability and some aspects of motor impairment and normality of movement. In addition, there was a significant difference in favour of no treatment compared with electrostimulation for an aspect of functional motor ability. For electrostimulation compared with placebo this review found that electrostimulation improved an aspect of functional motor ability. For electrostimulation compared with conventional physical therapy this review found that electrostimulation improved an aspect of motor impairment. There were no statistically significant differences between electrostimulation and control treatment for all other outcomes. However, these results need to be interpreted with reference to the following: (1) the majority of analyses only contained one trial; (2) variation was found between included trials in time after stroke, level of functional deficit, and dose of electrostimulation; and (3) the possibility of selection and detection bias in the majority of included trials. AUTHORS' CONCLUSIONS: At present, there are insufficient robust data to inform clinical use of electrostimulation for neuromuscular re-training. Research is needed to address specific questions about the type of electrostimulation that might be most effective, in what dose and at what time after stroke.
Assuntos
Terapia por Estimulação Elétrica/métodos , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral , Atividades Cotidianas , Terapia por Estimulação Elétrica/efeitos adversos , Humanos , Atividade Motora , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
These studies examined the effects of cycloheximide on the Na+/H+ antiporter in cultured opossum kidney cells. The effects of cycloheximide on antiporter activity depended on the basal level of activity. These data suggest that the Na+/H+ antiporter may be regulated by several processes which are sensitive to protein synthesis inhibition.
Assuntos
Proteínas de Transporte/metabolismo , Cicloeximida/farmacologia , Rim/metabolismo , Gambás/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Amilorida/farmacologia , Animais , Proteínas de Transporte/antagonistas & inibidores , Células Cultivadas , Rim/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio , Simportadores de Cloreto de Sódio-PotássioRESUMO
BACKGROUND: Treadmill training, with or without some body weight supported using a harness, is a method of treating walking after stroke. A systematic review is required to assess the cost, effectiveness, and acceptability of this treatment. OBJECTIVES: To assess the effectiveness of treadmill training and body weight support, individually or in combination, in the treatment of walking after stroke. The primary outcomes investigated were walking speed, endurance and dependency. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 2 March 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1980 to February 2005), CINAHL (1982 to February 2005) and PEDro (last searched 2 March 2005). In addition, we handsearched relevant conference proceedings, screened reference lists and contacted trialists to identify further published and unpublished trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled and cross-over trials of treadmill training and body weight support, individually or in combination, for the treatment of walking after stroke were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed quality. We contacted trialists for additional information. We used a fixed-effect model for analysis, but if heterogeneity existed a random-effects model was used. We analysed the results as weighted mean differences (WMD) for continuous variables and relative risk (RR) for dichotomous variables. MAIN RESULTS: Fifteen trials (622 participants) were included. There were no statistically significant differences between treadmill training, with or without body weight support, and other interventions for walking speed or dependence. Among participants who could walk independently at the start of treatment, treadmill training with body weight support tended to produce higher walking speeds (WMD 0.09 m/s, 95% confidence interval (CI) -0.02 to 0.20 for speed; fixed-effect), but this result was not statistically significant. An individual trial tended to support the use of treadmill training with body weight support for dependent walkers as compared to treadmill training alone. One of three individual trials indicated that independent walkers may benefit from treadmill training combined with other task-orientated exercise. However, data are very limited. Adverse events occurred more frequently in participants receiving treadmill training but these were not judged to be clinically serious events. AUTHORS' CONCLUSIONS: Overall no statistically significant effect of treadmill training with or without body weight support was detected. Although individual studies suggested that treadmill training with body weight support may be more effective than treadmill training alone and that treadmill training plus task-oriented exercise may be more effective than sham exercises, further trials are required to confirm these findings.