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1.
J Intellect Disabil Res ; 68(5): 387-445, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38414293

RESUMO

BACKGROUND: Adults with intellectual disabilities (IDs) are susceptible to multiple health risk behaviours such as alcohol consumption, smoking, low physical activity, sedentary behaviour and poor diet. Lifestyle modification interventions can prevent or reduce negative health consequences caused by these behaviours. We aim to determine the effectiveness of lifestyle modification interventions and their components in targeting health risk behaviours in adults with IDs. METHODS: A systematic review and meta-analysis were conducted. Electronic databases, clinical trial registries, grey literature and citations of systematic reviews and included studies were searched in January 2021 (updated February 2022). Randomised controlled trials and non-randomised controlled trials targeting alcohol consumption, smoking, low physical activity, sedentary behaviours and poor diet in adults (aged ≥ 18 years) with ID were included. Meta-analysis was conducted at the intervention level (pairwise and network meta-analysis) and the component-level (component network meta-analysis). Studies were coded using Michie's 19-item theory coding scheme and 94-item behaviour change taxonomies. Risk of bias was assessed using the Cochrane Risk of Bias (ROB) Version 2 and Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I). The study involved a patient and public involvement (PPI) group, including people with lived experience, who contributed extensively by shaping the methodology, providing valuable insights in interpreting results and organising of dissemination events. RESULTS: Our literature search identified 12 180 articles, of which 80 studies with 4805 participants were included in the review. The complexity of lifestyle modification intervention was dismantled by identifying six core components that influenced outcomes. Interventions targeting single or multiple health risk behaviours could have a single or combination of multiple core-components. Interventions (2 RCTS; 4 non-RCTs; 228 participants) targeting alcohol consumption and smoking behaviour were effective but based on limited evidence. Similarly, interventions targeting low physical activity only (16 RCTs; 17 non-RCTs; 1413 participants) or multiple behaviours (low physical activity only, sedentary behaviours and poor diet) (17 RCTs; 24 non-RCTs; 3164 participants) yielded mixed effectiveness in outcomes. Most interventions targeting low physical activity only or multiple behaviours generated positive effects on various outcomes while some interventions led to no change or worsened outcomes, which could be attributed to the presence of a single core-component or a combination of similar core components in interventions. The intervention-level meta-analysis for weight management outcomes showed that none of the interventions were associated with a statistically significant change in outcomes when compared with treatment-as-usual and each other. Interventions with core-components combination of energy deficit diet, aerobic exercise and behaviour change techniques showed the highest weight loss [mean difference (MD) = -3.61, 95% credible interval (CrI) -9.68 to 1.95] and those with core-components combination dietary advice and aerobic exercise showed a weight gain (MD 0.94, 95% CrI -3.93 to 4.91). Similar findings were found with the component network meta-analysis for which additional components were identified. Most studies had a high and moderate risk of bias. Various theories and behaviour change techniques were used in intervention development and adaptation. CONCLUSION: Our systematic review is the first to comprehensively explore lifestyle modification interventions targeting a range of single and multiple health risk behaviours in adults with ID, co-produced with people with lived experience. It has practical implications for future research as it highlights the importance of mixed-methods research in understanding lifestyle modification interventions and the need for population-specific improvements in the field (e.g., tailored interventions, development of evaluation instruments or tools, use of rigorous research methodologies and comprehensive reporting frameworks). Wide dissemination of related knowledge and the involvement of PPI groups, including people with lived experience, will help future researchers design interventions that consider the unique needs, desires and abilities of people with ID.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/reabilitação , Adulto , Comportamentos de Risco à Saúde , Exercício Físico , Consumo de Bebidas Alcoólicas/terapia , Consumo de Bebidas Alcoólicas/prevenção & controle
2.
J Intellect Disabil Res ; 68(4): 293-316, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38379511

RESUMO

BACKGROUND: Lifestyle modification interventions for adults with intellectual disabilities have had, to date, mixed effectiveness. This study aimed to understand how lifestyle modification interventions for adults with intellectual disabilities work, for whom they work and in what circumstances. METHODS: A realist evidence synthesis was conducted that incorporated input from adults with intellectual disabilities and expert researchers. Following the development of an initial programme theory based on key literature and input from people with lived experience and academics working in this field, five major databases (MEDLINE, EMBASE, CINAHL, PsycINFO and ASSIA) and clinical trial repositories were systematically searched. Data from 79 studies were synthesised to develop context, mechanism and outcome configurations (CMOCs). RESULTS: The contexts and mechanisms identified related to the ability of adults with intellectual disabilities to actively take part in the intervention, which in turn contributes to what works, for whom and in what circumstances. The included CMOCs related to support involvement, negotiating the balance between autonomy and behaviour change, fostering social connectedness and fun, accessibility and suitability of intervention strategies and delivery and broader behavioural pathways to lifestyle change. It is also essential to work with people with lived experiences when developing and evaluating interventions. CONCLUSIONS: Future lifestyle interventions research should be participatory in nature, and accessible data collection methods should also be explored as a way of including people with severe and profound intellectual disabilities in research. More emphasis should be given to the broader benefits of lifestyle change, such as opportunities for social interaction and connectedness.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/reabilitação , Adulto , Participação do Paciente
3.
Plant Pathol ; 68(8): 1472-1480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32406415

RESUMO

Virus-related degeneration constrains production of quality sweet potato seed, especially under open field conditions. Once in the open, virus-indexed seed is prone to virus infection leading to decline in performance. Insect-proof net tunnels have been proven to reduce virus infection under researcher management. However, their effectiveness under farmer-multiplier management is not known. This study investigated the ability of net tunnels to reduce degeneration in sweet potato under farmer-multiplier management. Infection and degeneration were assessed for two cultivars, Kabode and Polista, grown in net tunnels and open fields at two sites with varying virus pressures. There was zero virus incidence at both sites during the first five generations. Sweet potato feathery mottle virus and sweet potato chlorotic stunt virus were present in the last three generations, occurring singly or in combination to form sweet potato virus disease. Virus infection increased successively, with higher incidences recorded at the high virus pressure site. Seed degeneration modelling illustrated that for both varieties, degeneration was reduced by the maintenance of vines under net tunnel conditions. The time series of likely degeneration based on a generic model of yield loss suggested that, under the conditions experienced during the experimental period, infection and losses within the net tunnels would be limited. By comparison, in the open field most of the yield could be lost after a small number of generations without the input of seed with lower disease incidence. Adopting the technology at the farmer-multiplier level can increase availability of clean seed, particularly in high virus pressure areas.

4.
Oncogene ; 25(6): 838-48, 2006 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-16247474

RESUMO

c-FLIP inhibits caspase 8 activation and apoptosis mediated by death receptors such as Fas and DR5. We studied the effect of c-FLIP on the apoptotic response to chemotherapies used in colorectal cancer (CRC) (5-fluorouracil, oxaliplatin and irinotecan). Simultaneous downregulation of both c-FLIP splice forms c-FLIP(L) and c-FLIP(S) with siRNA synergistically enhanced chemotherapy-induced apoptosis in p53 wild-type (HCT116p53(+/+), RKO), null (HCT116p53(-/-)) and mutant (H630) CRC cell lines. Furthermore, overexpression of c-FLIP(L), but not c-FLIP(S), potently inhibited apoptosis induced by chemotherapy in HCT116p53(+/+) cells, suggesting that c-FLIP(L) was the more important splice form in mediating chemoresistance. In support of this, siRNA specifically targeted against c-FLIP(L) synergistically enhanced chemotherapy-induced apoptosis in a manner similar to the siRNA targeted against both splice forms. Inhibition of caspase 8 blocked the enhanced apoptosis induced by c-FLIP-targeted (FT) siRNA and chemotherapy. Furthermore, we found that downregulating cell surface DR5, but not Fas, also inhibited apoptosis induced by FT siRNA and chemotherapy. Interestingly, these effects were not dependent on activation of DR5 by its ligand TRAIL. These results indicate that c-FLIP inhibits TRAIL-independent, DR5- and caspase 8-dependent apoptosis in response to chemotherapy in CRC cells. Moreover, targeting c-FLIP in combination with existing chemotherapies may have therapeutic potential for the treatment of CRC.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Antineoplásicos/farmacologia , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Caspase 8 , Inibidores de Caspase , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Glicoproteínas de Membrana/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Mutação , Processamento de Proteína , RNA Interferente Pequeno , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Receptores do Fator de Necrose Tumoral/efeitos dos fármacos , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Receptor fas/efeitos dos fármacos , Receptor fas/genética , Receptor fas/metabolismo
5.
N Z Med J ; 129(1429): 64-70, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26914301

RESUMO

AIMS: Urinalysis for microscopy and culture is one of the most frequently requested tests for microbiology laboratories, particularly from elderly patients. This study sought to describe the clinical appropriateness of urinalysis from community-dwelling elderly patients and subsequent antibiotic prescription. METHODS: Demographic, laboratory, and antibiotic prescription data were collected on all samples submitted from patients ≥ 70 years during August 2014 to Labtests Auckland. In addition, clinical data were collected by questionnaire from a subgroup of 200 patients. RESULTS: During August 2014, approximately 7% of the Auckland population aged ≥ 70 years had urinalysis submitted. Urine dipstick was not routinely performed before specimen submission, particularly from patients living at home rather than a long-term care facility, and nearly 50% of samples were not cultured due to absence of pyuria. Escherichia coli was isolated from 23% of female and 7% of male specimens. E. coli isolates from our cohort were less susceptible to all antibiotics tested against compared with all E. coli isolated from all urines in 2014. Clinical indications were absent in 40% of the subgroup of patients. Antibiotic prescription within 7 days of urinalysis was common (36%). CONCLUSIONS: This study highlights the frequency of urinalysis testing among the elderly residing in the community. Clinical indications are often absent, and treatment of asymptomatic bacteriuria is likely to be contributing to excessive antibiotic prescription in this group of patients.


Assuntos
Infecções por Escherichia coli/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Procedimentos Desnecessários/estatística & dados numéricos , Urinálise/estatística & dados numéricos , Infecções Urinárias/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/urina , Feminino , Pesquisas sobre Atenção à Saúde , Instituição de Longa Permanência para Idosos , Humanos , Vida Independente , Assistência de Longa Duração , Masculino , Auditoria Médica , Nova Zelândia , Casas de Saúde , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Infecções Urinárias/urina
6.
Arch Intern Med ; 144(11): 2154-7, 1984 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6388521

RESUMO

In a randomized, controlled trial, ten patients with pulmonary heart disease due to severe chronic airflow obstruction were stratified into two groups: group 1 had clinical features of congestive heart failure during respiratory failure and were regularly receiving diuretics; group 2 had no such clinical features and were not receiving diuretics. In group 1, when placebo was substituted for diuretics, pulmonary edema developed in three patients; exercise performance and ventricular function of the remaining two patients deteriorated. In group 2, there was no difference in exercise tolerance or ventricular function between placebo and diuretic therapy. The clinical deterioration in group 1 was related to abnormal left ventricular function. Thus, diuretics benefit only patients who have clinical features of congestive heart failure. In patients with isolated abnormal right ventricular function, diuretics may be harmful.


Assuntos
Débito Cardíaco/efeitos dos fármacos , Diuréticos/uso terapêutico , Pneumopatias Obstrutivas/complicações , Pulmão/efeitos dos fármacos , Edema Pulmonar/tratamento farmacológico , Volume Sistólico/efeitos dos fármacos , Idoso , Ensaios Clínicos como Assunto , Método Duplo-Cego , Teste de Esforço , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/etiologia , Distribuição Aleatória , Testes de Função Respiratória , Insuficiência Respiratória/etiologia
7.
J Invest Dermatol ; 89(1): 82-6, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3110297

RESUMO

Significant levels of intracellular catecholamines were found in a human melanoma cell line and were enhanced by increasing the extracellular tyrosine concentration. Intracellular dopa, 5-cysteinyldopa, tyrosinase, and melanin also rose under these conditions. 5-HT (serotonin) was synthesized by the melanoma cells but further study was hindered by the high level of 5-HT in fetal calf serum. A 5-HT uptake antagonist, DU 24565 (6-nitroquipazine), was employed as an alternative method for studying 5-HT action. This compound, which in contrast to tunicamycin had no inhibitory effects on cell proliferation or tyrosinase activity, strongly inhibited melanization and decreased the levels of dopa, 5-cysteinyldopa, dopamine, noradrenaline, adrenaline, and 3,4-dihydroxyphenylacetic acid. DU 24565 had little effect on 5-HT or tyrosine accumulation in these cells but suppressed the uptake of extracellular dopa. The results show that human melanoma cells synthesize a wide range of biogenic amines in culture and suggest a new approach to regulating intracellular levels of dopa and of a variety of dopa products.


Assuntos
Melaninas/metabolismo , Melanoma/metabolismo , Quinolinas , Quipazina/análogos & derivados , Antagonistas da Serotonina/farmacologia , Catecolaminas/metabolismo , Linhagem Celular , Di-Hidroxifenilalanina/metabolismo , Humanos , Melanoma/patologia , Quipazina/farmacologia , Serotonina/metabolismo , Estimulação Química , Tirosina/metabolismo , Tirosina/farmacologia
8.
J Invest Dermatol ; 97(5): 868-73, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1680932

RESUMO

In cultured human melanoma cells, histamine H1 (mepyramine) and H2 receptor antagonists (cimetidine, ranitidine, impromidine) increased tyrosinase activity, whereas H2 agonists (dimaprit, nordimaprit) decreased activity. Mixtures of agonist and antagonist either decreased or increased tyrosinase activity, depending on the relative concentrations of each drug. Nordimaprit, the most effective inhibitor, lowered tyrosinase activity significantly within 36 h and caused a slower loss of tyrosinase protein as judged by reactivity with two monoclonal antibodies. Prolonged treatment of a melanotic cell line with nordimaprit led to complete loss of pigment, with no loss of the 56-kDa melanosomal antigen 1C11. Cells remained amelanotic for 8 weeks after removal of the drug and, even after 26 weeks, melanin content and tyrosinase expression and activity had not fully recovered. Nordimaprit increased the rate of degradation of tyrosinase and of nordimaprit binding proteins. Whereas nordimprit did not directly inhibit tyrosinase, lysates of treated cells contained an inhibitory activity that partitioned approximately equally across a 10-kDa ultrafiltration membrane. Overall, these results showed that melanogenesis can be controlled via histamine receptors, the mechanism for the H2 agonist nordimaprit consisting of three components: induction of a tyrosinase inhibitor, increased degradation of tyrosinase, and long-term down-regulation of tyrosinase expression.


Assuntos
Dimaprit/análogos & derivados , Melanoma/patologia , Monofenol Mono-Oxigenase/genética , Receptores Histamínicos H2/fisiologia , Citometria de Fluxo , Regulação Enzimológica da Expressão Gênica , Antagonistas dos Receptores H2 da Histamina/farmacologia , Humanos , Metionina , Radioisótopos de Enxofre , Tioureia/análogos & derivados , Tioureia/farmacologia , Células Tumorais Cultivadas
9.
J Invest Dermatol ; 90(4): 515-9, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3127479

RESUMO

Human tyrosinase was partially purified from the lysate of a melanoma cell line and used to immunize BALB/c mice. Spleen cells from the immunized mice were fused with a murine myeloma cell line (NS-1), yielding a hybridoma (5C12) that produced monoclonal antibody directed against tyrosinase. 5C12 antibody reacted with normal human melanocytes, neval cells, primary cultures of melanoma biopsies, and most melanoma cell lines, including amelanotic lines with very low levels of enzyme activity. No reaction was found with keratinocytes, lymphoid cells, fibroblasts, and nonmelanoma cell lines. The 5C12 antibody was used to affinity-purify tyrosinase directly from a cell lysate, giving a single protein of 60,000 daltons, electrophoretically identical with enzyme activity and immunoreactivity with 5C12 antibody. Treatment of melanoma cells with periodate significantly reduced antigenicity. It can be inferred from these results that 5C12 antibody is directed against a carbohydrate moiety present in active and inactive tyrosinase, and that amelanotic melanoma cells may contain significant levels of the latter protein.


Assuntos
Anticorpos Monoclonais/imunologia , Catecol Oxidase/imunologia , Melanoma/patologia , Monofenol Mono-Oxigenase/imunologia , Animais , Especificidade de Anticorpos , Fusão Celular , Linhagem Celular , Eletroforese em Gel de Poliacrilamida , Humanos , Melanócitos/enzimologia , Melanoma/enzimologia , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Monofenol Mono-Oxigenase/isolamento & purificação
10.
Am J Med ; 96(6A): 45S-54S, 1994 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-8017467

RESUMO

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.


Assuntos
Anticolesterolemiantes/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Genfibrozila/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Indóis/administração & dosagem , Adulto , Idoso , Análise de Variância , Anticolesterolemiantes/efeitos adversos , Método Duplo-Cego , Ácidos Graxos Monoinsaturados/efeitos adversos , Feminino , Fluvastatina , Genfibrozila/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia/sangue , Indóis/efeitos adversos , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Biochem Pharmacol ; 43(10): 2083-90, 1992 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-1534659

RESUMO

Human melanoma cells were treated in culture with the histamine (H2) agonist S-(3-(N-N-dimethylamino)propyl)isothiourea (dimaprit), a partial agonist, S-(2-(N,N-dimethylamino)ethyl)-isothiourea (nordimaprit), and two analogues of nordimaprit, S-(2-(N,N-diethylamino)ethyl)isothiourea (DENOR) and S-(2-(N,N-diisopropylamino)ethyl)isothiourea (DINOR), to investigate the effects on toxicity and tyrosinase activity. Cell survival studies showed highest toxicity in the constitutively pigmented human melanoma cell line MM418, DINOR being the most effective agent. Toxicity was not blocked by the H2 antagonist cimetidine. Dimaprit and its derivatives decreased tyrosinase activity in the amelanotic human melanoma cell line MM96E and inhibited expression of a melanosomal antigen. Loss of tyrosinase activity could be prevented by cimetidine and ranitidine, an H2 antagonist. Although the tyrosinase activity in MM418 cells was much more resistant to inhibition by these agents compared with that in MM96E cells, prolonged growth in the presence of non-toxic levels of DINOR caused a decrease in tyrosinase activity and subsequent depigmentation. Ultrastructural examination of the depigmented cells showed a decrease in the number of melanized melanosomes and the appearance of premelanosomes. These results indicate that bulky substituents on the tertiary amine group in nordimaprit significantly enhance potency for depigmentation and cell killing but only the former effect is mediated by the H2 receptor.


Assuntos
Receptores Histamínicos H2 , Tioureia/análogos & derivados , Tioureia/farmacologia , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular , Cimetidina/farmacologia , Dimaprit , Humanos , Immunoblotting , Melanoma/metabolismo , Microscopia Eletrônica , Monofenol Mono-Oxigenase/análise , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pigmentação/efeitos dos fármacos , Ranitidina/farmacologia , Receptores Histamínicos H2/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos dos fármacos
12.
J Am Soc Mass Spectrom ; 12(5): 557-64, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11349953

RESUMO

The ion-molecule reactivity of the products formed in the association reactions of HCNH+ with C2H2 (C3H4N+) and C2H4 (C3H6N+) has been investigated to provide information on the structures of the adducts thus formed. The C3H4N+ and C3H6N+ adducts were formed in the reaction flow tube of a flowing afterglow sourced-selected ion flow tube (FA-SIFT) and their reactivity with a neutral molecular "probe" examined. The reactivity of possible known structural isomers for the C3H4N+ and C3H6N+ ions was investigated in both the FA-SIFT and an ion cyclotron resonance spectrometer (ICR). Ab initio investigations of the potential energy surfaces for both structures at the G2(MP2) level have also been performed and structures corresponding to local minima on both surfaces have been identified and evaluated. The results of these experimental and theoretical studies show that at room temperature, the C3H4N+ adduct ion contains two isomers; a less reactive one that is likely to be a four-membered cyclic covalent isomer (approximately 70%) and a faster reacting component that is probably an electrostatic complex (approximately 30%). The C3H6N+ adduct ion formed from HCNH+ + C2H4 at room temperature is a single isomer that is likely to be the four-membered covalently bound cyclic CH2CH2CHNH+ species.

13.
Melanoma Res ; 1(2): 97-104, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1823629

RESUMO

Systemically administered 4-S-cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-CAP inhibited the growth of xenografts of a human melanoma cell line but not of an ovarian tumour cell line. No selective cytotoxicity for melanoma cells was observed in culture, however. Further study of the in vitro mechanism of 4-S-CAP toxicity showed minimal inhibition of tyrosinase activity or DNA, RNA and protein synthesis, and there was no phase-specific arrest of the cell cycle. However, expression of an 80 kD melanosomal antigen was decreased. Cytotoxicity of 4-S-CAP in culture was decreased by simultaneous treatment with a monoamine oxidase inhibitor. An affinity column prepared from 4-S-CAP retained several proteins from a melanoma cell lysate. One protein, found also in HeLa cells, was identified by N-terminal sequencing as protein disulphide isomerase, a molecule which has multiple roles in the modification of secretory proteins. These results identify a protein target for 4-S-CAP as one possible mechanism of cytotoxicity.


Assuntos
Antineoplásicos/farmacologia , Cisteamina/análogos & derivados , Isomerases/antagonistas & inibidores , Melanoma Experimental/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Fenóis/farmacologia , Sequência de Aminoácidos , Animais , Antineoplásicos/uso terapêutico , Cisteamina/farmacologia , Cisteamina/uso terapêutico , Di-Hidroxifenilalanina/metabolismo , Feminino , Células HeLa/efeitos dos fármacos , Células HeLa/enzimologia , Humanos , Melanoma/patologia , Camundongos , Dados de Sequência Molecular , Monoaminoxidase/metabolismo , Transplante de Neoplasias , Neoplasias Ovarianas/patologia , Fenóis/uso terapêutico , Isomerases de Dissulfetos de Proteínas , Transplante Heterólogo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/enzimologia , Células Tumorais Cultivadas/patologia
14.
Redox Rep ; 5(2-3): 151-3, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10939300

RESUMO

We show how the concentration of the breath gases ammonia, acetone, and isoprene vary with time during exercise using the new selected ion flow tube mass spectrometry (SIFT-MS) technique. The expired breath concentrations of ammonia, acetone and isoprene were observed within the range of 50-500, 100-1400 and 5-400 ppb, respectively. Increasing acetone levels were observed for most subjects during the exercise period. However, isoprene levels decreased with time during exercise. Older subjects showed higher levels of isoprene compared with younger subjects. The ammonia time profile with exercise showed both decreasing and increasing patterns for different subjects.


Assuntos
Acetona/análise , Amônia/análise , Butadienos/análise , Exercício Físico/fisiologia , Hemiterpenos , Pentanos , Esportes/fisiologia , Adolescente , Adulto , Testes Respiratórios , Feminino , Humanos , Masculino , Espectrometria de Massas/instrumentação , Espectrometria de Massas/métodos , Corrida , Fatores de Tempo
15.
Redox Rep ; 6(3): 185-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11523595

RESUMO

The selected ion flow tube mass spectrometry (SIFT-MS) technique enables real time analysis of trace volatiles at ppb levels without preconcentration steps or chemical derivatization. Most previous studies of trace compounds on the breath were analyzed using gas chromatography where enhanced detection sensitivity was achieved by concentrating the breath using cryogenic or adsorption trapping techniques. In this paper, we have examined volatile organic substances, isoprene, acetone, ammonia and ethanol in breath before and after smoking a cigarette. It is interesting that isoprene levels increased in all the subjects after smoking one cigarette with a mean increase of 70%. The mean increase for acetone was found to be 22%. In contrast to isoprene, a decreasing ethanol level was observed in all the subjects except one with the negative mean decrease of 28%. Further SIFT-MS studies also have high-lighted some organic substances produced even by unburned cigarettes, US and New Zealand products. Certain US brands have shown much higher levels of volatile species than cigarettes produced in New Zealand.


Assuntos
Acetona/análise , Amônia/análise , Testes Respiratórios/métodos , Butadienos/análise , Etanol/análise , Hemiterpenos , Espectrometria de Massas/métodos , Pentanos , Fumar/metabolismo , Adulto , Sistemas Computacionais , Feminino , Humanos , Masculino , Metanol/análise , Pessoa de Meia-Idade , Nova Zelândia , Propilenoglicol/análise , Estados Unidos , Volatilização
16.
Seizure ; 13(1): 3-14, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14741177

RESUMO

A sizeable literature focusing on QOL in children and adolescents with epilepsy has been produced over the last few years. However, relatively little emphasis has been placed on defining these issues from direct exploration of children's and adolescents' views. Qualitative methodologies are proposed in this review as an appropriate means of eliciting such information. This review systematically investigated the extent to which studies of QOL in children and adolescents with epilepsy have used recognised qualitative methodology. Articles for inclusion were identified by searching the term 'epilepsy', combined with 'adolescent(s) and/or child(ren)' and 'psychosocial and/or quality of life'. Selected articles were reviewed and rated using CASP Guidelines for qualitative research by two independent raters. Seventeen studies were retrieved through literature search. Of these six used some form of qualitative methodology either individually or combined with quantitative methods. However, only one study met quality criteria for selection in this systematic review. A summary of both selected and excluded studies is presented and methodological limitations discussed. Recommendations for appropriate methodology for investigation of QOL issues in children and adolescents are given.


Assuntos
Epilepsia/psicologia , Nível de Saúde , Qualidade de Vida , Projetos de Pesquisa/normas , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Armazenamento e Recuperação da Informação , Masculino , Psicometria , Inquéritos e Questionários
17.
Seizure ; 13(1): 15-31, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14741178

RESUMO

The majority of previous studies investigating the impact of epilepsy on the QOL of adolescents have used proxy opinions from clinicians and/or parents. This study highlights the need for research to investigate QOL from the direct perspective of adolescents and consider issues in the context of a developmental perspective. A focus group technique was used. Twenty-two adolescents aged between 12 years 4 months and 18 years 0 months (6 males and 16 females) were stratified by age (12-13, 14-15 and 16+ years) into six focus groups. Data were transcribed and QSR NUD*IST 4.0 was used to help generate central themes. Several procedures were undertaken to increase validity and reliability of findings. Analysis identified two main themes comprising (a) issues related to adolescent development (identity formation) and (b) epilepsy related variables, with five and four main sub-themes, respectively ('peer acceptance', 'development of autonomy', 'school related issues', 'epilepsy as part of me' and 'future', and 'medication issues', 'seizures', 'knowledge of epilepsy' and 'sense of uncertainty'). The main issues related to peer acceptance and development of autonomy. In contrast to previous studies, academic difficulties were not highlighted as an issue. No significant age-related differences in issues were identified. A conceptual model representing these findings is presented and clinical implications and suggestions for future research are reported.


Assuntos
Epilepsia/psicologia , Grupos Focais/métodos , Psicologia , Qualidade de Vida , Adolescente , Fatores Etários , Atitude Frente a Saúde , Criança , Epilepsia/epidemiologia , Feminino , Indicadores Básicos de Saúde , Inquéritos Epidemiológicos , Humanos , Identificação Psicológica , Relações Interpessoais , Masculino , Modelos Psicológicos , Autonomia Pessoal , Psicologia do Adolescente , Reprodutibilidade dos Testes , Convulsões/psicologia , Comportamento Social , Inquéritos e Questionários
18.
J Environ Qual ; 31(2): 515-24, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11931442

RESUMO

A new technique is presented for the rapid, high-resolution identification and quantification of multiple trace gases above soils, at concentrations down to 0.01 microL L(-1) (10 ppb). The technique, selected ion flow tube mass spectrometry (SIFT-MS), utilizes chemical ionization reagent ions that react with trace gases but not with the major air components (N2, O2, Ar, CO2). This allows the real-time measurement of multiple trace gases without the need for preconcentration, trapping, or chromatographic separation. The technique is demonstrated by monitoring the emission of ammonia and nitric oxide, and the search for volatile organics, above containerized soil samples treated with synthetic cattle urine. In this model system, NH3 emissions peaked after 24 h at 2000 nmol m(-2) s(-1) and integrated to approximately 7% of the urea N applied, while NO emissions peaked about 25 d after urine addition at approximately 140 nmol m(-2) s(-1) and integrated to approximately 10% of the applied urea N. The monitoring of organics along with NH3 and NO was demonstrated in soils treated with synthetic urine, pyridine, and dimethylamine. No emission of volatile nitrogen organics from the urine treatments was observed at levels >0.01% of the applied nitrogen. The SIFT method allows the simultaneous in situ measurement of multiple gas components with a high spatial resolution of < 10 cm and time resolution <20 s. These capabilities allow, for example, identification of emission hotspots, and measurement of localized and rapid variations above agricultural and contaminated soils, as well as integrated emissions over longer periods.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Agricultura , Gases , Íons , Espectrometria de Massas/métodos , Sensibilidade e Especificidade , Poluentes do Solo , Volatilização
19.
Percept Mot Skills ; 72(1): 75-9, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2038537

RESUMO

The influences of early crawling experience on motor skill development were examined in children identified by parents as crawlers or noncrawlers during early infancy. Relative to the performance of crawlers, noncrawlers showed lower average and subtest-specific performance on selected measures of the Miller Assessment for Preschoolers. These results, interpreted through Ayres' sensory integration theory and applied to current occupational therapy practice, support Farber's hypothesized importance of early crawling experience in the development of sensory and motor systems of the body and general motor skill development.


Assuntos
Desenvolvimento Infantil , Comportamento Exploratório , Locomoção , Destreza Motora , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Orientação , Desempenho Psicomotor
20.
Percept Mot Skills ; 79(2): 907-11, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7532855

RESUMO

The effectiveness of an early intervention program to remediate developmental delays in children age birth to 3 years was examined in part- and full-time groups (Study 1). Significant improvements on age-appropriate measures of developmental standing were observed for both groups, with the greatest gains observed for the full-time group. In Study 2, the stress of parents with developmentally delayed children was measured on the Parental Stress Inventory. Reductions in stress related to children's characteristics and dysfunctional parenting skills were observed on some subscales, supporting prior research which indicated extension of the outcomes of early intervention beyond the child was desirable.


Assuntos
Deficiências do Desenvolvimento/reabilitação , Intervenção Educacional Precoce/métodos , Pré-Escolar , Efeitos Psicossociais da Doença , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes Neuropsicológicos , Pais/psicologia , Equipe de Assistência ao Paciente , Inventário de Personalidade , Resultado do Tratamento
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