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1.
Curr Oncol ; 21(3): e441-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24940104

RESUMO

BACKGROUND: Understanding factors relating to the perception of wait time by patients is key to improving the patient experience. METHODS: We surveyed 122 breast and 90 prostate cancer patients presenting at clinics or listed on the cancer registry in Newfoundland and Labrador and reviewed their charts. We compared the wait time (first visit to diagnosis) and the wait-related satisfaction for breast and prostate cancer patients who received regular screening tests and whose cancer was screening test-detected ("screen/screen"); who received regular screening tests and whose cancer was symptomatic ("screen/symptomatic"); who did not receive regular screening tests and whose cancer was screen test-detected ("no screen/screen"); and who did not receive regular screening tests and whose cancer was symptomatic ("no screen/symptomatic"). RESULTS: Although there were no group differences with respect to having a long wait (greater than the median of 47.5 days) for breast cancer patients (47.8% screen/screen, 54.7% screen/symptomatic, 50.0% no screen/ screen, 40.0% no screen/symptomatic; p = 0.814), a smaller proportion of the screen/symptomatic patients were satisfied with their wait (72.5% screen/ screen, 56.4% screen/symptomatic, 100% no screen/ screen, 90.9% no screen/symptomatic; p = 0.048). A larger proportion of screen/symptomatic prostate cancer patients had long waits (>104.5 days: 41.3% screen/screen, 92.0% screen/symptomatic, 46.0% no screen/screen, 40.0% no screen/symptomatic; p = 0.011) and a smaller proportion of screen/ symptomatic patients were satisfied with their wait (71.2% screen/screen, 30.8% screen/symptomatic, 76.9% no screen/screen, 90.9% no screen/symptomatic; p = 0.008). CONCLUSIONS: Diagnosis-related wait times and satisfaction were poorest among patients who received regular screening tests but whose cancer was not detected by those tests.

2.
Am J Ind Med ; 53(8): 836-41, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20213748

RESUMO

BACKGROUND: Exposure to methyl isocyanate and other toxic gases in Bhopal, India, on December 3, 1984 resulted in thousands of acute deaths, pregnancy loss and long-term effects. METHODS: From 1985 to 2007, we conducted successive surveys of vital status and health to determine whether the exposure of parents to toxic gases in the Bhopal incident affected the 5-year survival and anthropometric variables of their offspring. RESULTS: Initial 5-year mortality of offspring of exposed parents was very high. Male but not female offspring who were exposed to gases in utero or who were born to exposed parents were stunted in growth until puberty, which was followed by a period of accelerated growth. Results also suggest a post-puberty effect on head circumference of females exposed to gases in utero. CONCLUSION: Exposure of pregnant women to toxic gases in Bhopal in 1984 resulted in high pregnancy loss, increased first 5-year mortality and delayed development of male progeny.


Assuntos
Transtornos do Crescimento/induzido quimicamente , Isocianatos/toxicidade , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Praguicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Análise de Variância , Antropometria , Antidrepanocíticos/toxicidade , Estatura , Tamanho Corporal , Peso Corporal , Vazamento de Resíduos Químicos/estatística & dados numéricos , Pré-Escolar , Feminino , Transtornos do Crescimento/epidemiologia , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Masculino , Pico do Fluxo Expiratório , Gravidez , Puberdade , Fatores Sexuais , Estresse Fisiológico
3.
Neurology ; 53(3): 485-90, 1999 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-10449108

RESUMO

BACKGROUND: Utz et al., in a study of identical twins discordant for MS, showed that antigen-stimulated T cells from the MS twins have a major shift in their T-cell receptor (TCR) repertoires when compared with the healthy twins. We hypothesized that a shift in the TCR repertoire precedes the onset of MS and tested this hypothesis by studying unstimulated naive T cells because the TCR repertoires of these cells are largely unaffected by disease. OBJECTIVE: To investigate whether unstimulated naive T cells from MS patients have a detectable shift in their TCR repertoires. METHODS: We analyzed the TCR J beta (TCRBJ) repertoires of naive T cells from identical twin pairs discordant for MS, healthy identical twin pairs, healthy unrelated pairs, and unrelated MS patient pairs. The correlation coefficient (r value) was used as a measure of similarity of TCRBJ repertoires in each pair of individuals. Fisher's z transformation was then used to test for the significance of the difference between the r values from different pairs. RESULTS: The TCRBJ repertoires of the discordant MS twin pairs were significantly different from those of the healthy identical twin pairs, whereas MS patient pairs had TCRBJ repertoires similar to those of the healthy unrelated pairs formed from healthy twin pairs and discordant MS twin pairs. CONCLUSIONS: MS patients have a major shift in their naive T-cell TCRBJ repertoires compared with healthy individuals, implying that this shift precedes the disease onset. This shift could represent the nongenetic factor that explains MS discordance in genetically identical individuals.


Assuntos
Esclerose Múltipla/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Adolescente , Adulto , Doenças em Gêmeos , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Receptores de Antígenos de Linfócitos T/genética
4.
J Hypertens ; 18(5): 567-73, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10826559

RESUMO

BACKGROUND AND OBJECTIVES: In spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs. METHODS AND RESULTS: Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar- Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. CONCLUSIONS: Dietary alpha-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.


Assuntos
Suplementos Nutricionais , Hipertensão/dietoterapia , Ácido Tióctico/administração & dosagem , Aldeídos/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Glicemia/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cálcio/sangue , Hiperplasia , Hipertensão/patologia , Hipertensão/fisiopatologia , Insulina/sangue , Rim/irrigação sanguínea , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Músculo Liso Vascular/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
5.
Can J Public Health ; 87(2): 97-100, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8753636

RESUMO

Measles antibody levels were determined by the plaque reduction neutralization (PRN) test in 580 one-year-old children before vaccination and four to six weeks after MMR II vaccination. Fifty-one (8.8%) had maternally derived measles antibody at prevaccination, and this was more common among children of women born before 1967 (10.6%) vs. 4.3%; p < 0.01). Among those with maternal antibody, only 22 (43.1%) responded with a protective PRN titre of over 120, in contrast to 463 (87.5%) of the 529 without maternal antibody at prevaccination (p < 0.0001). Also, the geometric mean titre was significantly lower for the former (114.1 vs. 378.5; p < 0.0001). Overall, 15 (2.6%) of the 580 children had no antibody response after vaccination, and a further 80 (13.8%) had a subprotective response (PRN titre < 120). This lack of response could not be attributed entirely to the presence of maternal measles antibody at the time of vaccination. The MMR II vaccine may not be sufficiently immunogenic in inducing adequate measles antibody response after a single dose given at one year of age.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Vacina contra Caxumba/imunologia , Vacina contra Rubéola/imunologia , Fatores Etários , Feminino , Humanos , Imunidade Materno-Adquirida , Esquemas de Imunização , Lactente , Masculino , Idade Materna , Vacina contra Sarampo-Caxumba-Rubéola , Testes de Neutralização , Falha de Tratamento , Vacinas Combinadas/imunologia
6.
Can J Public Health ; 87(6): 407-10, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9009400

RESUMO

Measles serum antibody levels were determined by plaque reduction neutralization (PRN) test in 1,075 children in the age bracket of 5 to 17 years who received a single dose of measles-mumps-rubella (MMR II) vaccine at one year of age. Of these, 297 children (28%) had measles PRN titres < 120 which may not be protective against measles infection. The proportion of susceptible children by age ranged from 14 to 35%; however, there was no consistent age-dependent trend in susceptibility rates. The study data indicate the decline in protective immunity occurs before five years of age, and the proportion susceptible increases only slightly thereafter. This supports the current move towards a two-dose immunization strategy in the control and elimination of measles, with the second dose being given before school entry. The present data also underscore the need to consider a mass catch-up immunization program in the interim to prevent potential outbreaks of measles in school settings. The combination of the above approaches, if implemented as soon as possible, can potentially eliminate indigenous measles in Canada by the year 2000, the target date set by the Pan American Health Organization.


Assuntos
Surtos de Doenças/prevenção & controle , Programas de Imunização/organização & administração , Sarampo/prevenção & controle , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Humanos , Sarampo/epidemiologia , Sarampo/imunologia , Terra Nova e Labrador/epidemiologia , Instituições Acadêmicas , Estudos Soroepidemiológicos
7.
Can J Infect Dis ; 8(2): 85-8, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22514481

RESUMO

OBJECTIVE: To determine the prevailing levels of rubella immunity among school-aged children who received a single dose of measles-mumps-rubella (MMR) vaccine at one year of age. DESIGN: Cross-sectional study with a two stage cluster sampling of randomly picked schools across the province of Newfoundland. STUDY POPULATION AND METHODS: A total of 1053, five to 17-year-old children were enrolled; vaccination history was verified through official records; and a sample of blood was taken. Rubella immunity was determined by enzyme immunoassay based on a serum antibody protective cut-off titre of more than 10 IU. RESULTS: A total of 145 (13.8%) were found to be nonimmune. The rate of susceptibility ranged from 3.2% to 25.9% for different age groups. The proportion susceptible was significantly higher at 16.5% in the age group eight to 17 years old versus 3.9% for the age group five to eight years old (χ(2)=24.08; df=1, P<0.001). There was a significant regression of logarithm titre values on the age of children with an average decline in titre values of 8.1% per annum. CONCLUSIONS: A substantial number of those who were given a single dose of MMR II vaccine may not have protective immunity against rubella as they reach prime reproductive age. There is a definite need to consider a two-dose rubella vaccination strategy in Canada, and these data suggest the second dose given after eight years of age will be most beneficial. In the move towards a routine two-dose measles vaccination strategy in Canada, the MMR II vaccine is being used for the second dose and given either at 18 months of age or at school entry. While this approach will have an overall beneficial effect, the impact of the above timing of the second dose on long term rubella immunity cannot be predicted at this time. These data also underscore the continuing need for prenatal rubella screening program.

9.
Clin Exp Immunol ; 143(2): 305-13, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16412055

RESUMO

We have reported previously that naive T cells from relapsing-remitting multiple sclerosis (RRMS) patients have T cell receptor (TCR) repertoire shifts, but the basis of these TCR repertoire shifts was uncertain. Here, we questioned whether RRMS patients have altered naive CD4 and CD8 T cell homeostasis by studying homeostatic proliferation and thymic production in RRMS patients and healthy controls. We measured thymic production by quantifying signal joint T cell receptor excision circles (sjTRECs). Both naive T subsets from controls showed an age-associated decrease in sjTRECs, i.e. evidence of progressive thymic involution, but we detected no age-associated decrease in sjTRECs in RRMS patients. Instead, naive CD8 T cells from patients had lower sjTRECs (P = 0.012) and higher Ki-67 proliferation levels (P = 0.04) than controls. Naive CD4 T cell sjTRECs did not differ between patients and controls. However, in RRMS these sjTRECs correlated strongly with CD31, a marker expressed by newly generated CD4 T cells but not by naive CD4 T cells that have undergone homeostatic proliferation. HLA-DR2 positivity correlated negatively with naive CD4 T cell CD31 expression in RRMS (P = 0.002). We conclude in RRMS that naive T subsets have homeostatic abnormalities due probably to peripheral (non-thymic) mechanisms. These abnormalities could have relevance for MS pathogenesis, as naive T cell changes may precede MS onset.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Homeostase/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Timo/imunologia , Divisão Celular/imunologia , Rearranjo Gênico do Linfócito T/genética , Rearranjo Gênico do Linfócito T/imunologia , Genes Codificadores dos Receptores de Linfócitos T/genética , Genes Codificadores dos Receptores de Linfócitos T/imunologia , Antígeno HLA-DR2/análise , Homeostase/genética , Humanos , Imunofenotipagem/métodos , Antígeno Ki-67/análise , Esclerose Múltipla Recidivante-Remitente/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Receptores Imunológicos/imunologia , Reprodutibilidade dos Testes
10.
J Pediatr ; 127(3): 432-4, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7658276

RESUMO

The effect of concurrent afebrile viral upper respiratory tract infection (URI) on measles and rubella serum antibody response after measles-mumps-rubella (MMR) vaccination was determined in 580 1-year-old children, 369 with URI and 211 without URI, with the use of preimmunization and postimmunization sera. The presence of URI during the preceding 28 days, at the time of, or up to 7 days after immunization had no effect on the antibody response to either the measles or the rubella component of the vaccine. These findings support the recommendation that MMR vaccine be give to children at the recommended age regardless of the presence of afebrile viral URI.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Vacina contra Caxumba/imunologia , Infecções Respiratórias/imunologia , Vacina contra Rubéola/imunologia , Vírus da Rubéola/imunologia , Humanos , Lactente , Terra Nova e Labrador , Estudos Prospectivos , Fatores de Tempo , Vacinas Combinadas/imunologia
11.
Clin Exp Immunol ; 134(3): 532-7, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14632762

RESUMO

CD4 T-cells have an important role in the autoimmune response in multiple sclerosis (MS). We investigate the possibility that a shift occurs in the T-cell receptor (TR) repertoire of identical twins discordant for MS. We compare the CDR3 spectratype distributions of 24 different TR V beta (TRBV) segments in naïve CD4 T-cells from discordant MS twins and from healthy identical twins. We also compare the CDR3 spectratype distributions in unrelated healthy pairs, formed by combining members of different healthy twins, with the CDR3 spectratype distributions in unrelated pairs of MS patients and in unrelated pairs of their apparently healthy cotwins, formed by combining members of different discordant twins. We use the correlation coefficient (r-value) as a measure of similarity of CDR3 spectratypes in each pair, and we test for the significance of the difference between r-values from the different pairs. We observe that the r-value for the CDR3 spectratype distributions among discordant twins differs significantly from the corresponding r-value for the healthy twins for two TRBV segments. Further, the r-values, for both the unrelated MS patient pairs and the unrelated pairs of their apparently healthy cotwins, differ significantly from the r-values for healthy unrelated pairs of individuals. We conclude that both the MS patients and their apparently healthy cotwins have shifts in their CDR3 repertoires. Because we study naïve CD4 T-cells, we postulate that CDR3 repertoire shifts precede MS and predispose to MS, but are unlikely to be sufficient to cause MS.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Doenças em Gêmeos , Esclerose Múltipla/imunologia , Complexo Receptor-CD3 de Antígeno de Linfócitos T/análise , Gêmeos Monozigóticos , Adulto , Autorradiografia , Complexo CD3/análise , Estudos de Casos e Controles , Interpretação Estatística de Dados , Suscetibilidade a Doenças/imunologia , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Complexo Receptor-CD3 de Antígeno de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise
12.
J Clin Microbiol ; 33(4): 811-5, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7790442

RESUMO

Four commercially available enzyme immunoassay (EIA) kits were evaluated in comparison with the plaque reduction neutralization (PRN) test for detection of measles virus antibody. The EIA kits, Enzygnost (Behring), Diamedix, Vidas (bioMerieux Vitek), and Measlestat (Biowhittaker), were assessed with two PRN cutoff titers: a PRN titer of 8, the lowest detectable antibody level by the PRN test under the test conditions, and a titer of 120, which has been shown to be the minimum protective antibody titer. At a PRN cutoff titer of 8, the sensitivity was 88.2, 91.1, 74.6, and 69.8% for Behring, Diamedix, Vidas, and Biowhittaker EIA tests, respectively, with negative predictive values ranging from 22.7 to 45.5%. The specificity was 93.8% for Diamedix and 100% for the rest. At a PRN cutoff titer of 120, the sensitivity and specificity, respectively, were 100 and 90.7% (Behring), 98.2 and 58.8% (Diamedix), 90.6 and 94.5% (Vidas), and 85.7 and 96.4% (Biowhittaker). At this PRN cutoff titer, the negative predictive values of all EIA tests improved considerably, ranging from 70.7 to 100%. The EIA results showed an excellent association with PRN results when the PRN titers of the test samples were either < 8 or > 1,052. Discrepancies occurred especially when testing samples having PRN titers in the range of 8 to 120, indicating lack of sensitivity of the EIA tests in detecting measles virus antibody at low levels. Maternally derived measles virus antibody at this level has been shown to interfere with measles vaccine response in children and hence has implications from the standpoint of measles immunization. The ready availability, ease of operation, and rapid turnaround time are strong plus points of the EIA kits, and they could be useful in a clinical laboratory setting for routine application, but they may have limited use in vaccine-related studies and seroepidemiological surveys.


Assuntos
Anticorpos Antivirais/sangue , Técnicas Imunoenzimáticas , Vírus do Sarampo/imunologia , Testes de Neutralização/métodos , Ensaio de Placa Viral/métodos , Criança , Estudos de Avaliação como Assunto , Humanos , Técnicas Imunoenzimáticas/estatística & dados numéricos , Sarampo/imunologia , Sarampo/prevenção & controle , Vacina contra Sarampo/imunologia , Testes de Neutralização/estatística & dados numéricos , Padrões de Referência , Sensibilidade e Especificidade , Ensaio de Placa Viral/estatística & dados numéricos
13.
Artery ; 23(1): 10-36, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-10846614

RESUMO

Methylglyoxal, a highly reactive endogenous aldehyde is formed in the tissue of humans and animals as an intermediate of glucose and fructose metabolism. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet [Ca2+]i, circulating nitric oxide levels, tissue aldehyde conjugates and renal vascular changes in chronic methyglyoxal treated Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals, age seven weeks, were divided into three groups of six animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-methylglyoxal (chow diet and methyglyoxal in drinking water); WKY-methyglyoxal + NAC (1.5% NAC in diet and methylglyoxal in drinking water) for the next 18 weeks. Methylgyoxal in drinking water was given at a concentration of 0.2% during weeks 0-5; 0.4%, weeks 6-10; and 0.8%, weeks 11-18. After 18 weeks systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were significantly higher and serum nitric oxide levels lower in methylglyoxal treated rats. Methylglyoxal treated rats also showed smooth muscle cell hyperplasia in the small artery and arterioles of the kidney. N-acetyl cysteine, an aldehyde binding thiol compound, prevented these changes.


Assuntos
Acetilcisteína/uso terapêutico , Hipertensão/induzido quimicamente , Aldeído Pirúvico/toxicidade , Acetilcisteína/administração & dosagem , Aldeídos/análise , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Plaquetas/química , Plaquetas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Metabolismo dos Carboidratos , Dieta , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Hiperplasia , Hipertensão/prevenção & controle , Resistência à Insulina , Rim/irrigação sanguínea , Masculino , Músculo Esquelético/química , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Nitratos/sangue , Óxido Nítrico/sangue , Nitritos/sangue , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos WKY , Artéria Renal/efeitos dos fármacos , Artéria Renal/patologia , Vísceras/química
14.
Mol Cell Biochem ; 218(1-2): 97-103, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11330844

RESUMO

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. Vitamin C can increase tissue cysteine and glutathione levels. The aim of the present study was to investigate whether a dietary supplementation of vitamin C can lower tissue aldehydes and blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into 3 groups of 6 animals each. Animals in the WKY-control group and SHR-control group were given a normal diet and the SHR-vitamin C group a diet supplemented with vitamin C (1000 mg/kg feed) for the next 9 weeks. After nine weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared to WKY controls and the SHR-vitamin C group. SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin C supplementation in SHRs lowered the systolic blood pressure, tissue aldehyde conjugates and attenuated adverse renal vascular changes.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Fígado/efeitos dos fármacos , Aldeídos/metabolismo , Animais , Plaquetas/metabolismo , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Suplementos Nutricionais , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hiperplasia/patologia , Hipertensão/patologia , Fígado/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
15.
Mol Cell Biochem ; 238(1-2): 111-7, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12349898

RESUMO

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. Vitamin E increases tissue glutathione levels--a storage form of cysteine. The aim of the present study was to investigate whether a dietary supplementation of vitamin E lowers blood pressure and prevents renal vascular changes by normalizing tissue aldehyde conjugates and cytosolic [Ca2+] in SHRs. Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the WKY-control group and SHR-control group were given a normal diet and the SHR-vitamin E group a diet supplemented with vitamin E (34 mg/ kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared to WKY controls and the SHR-vitamin E group. SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidney. Dietary vitamin E supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+], tissue aldehyde conjugates and attenuated adverse renal vascular changes.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Vitamina E/farmacologia , Administração Oral , Aldeídos/análise , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Suplementos Nutricionais , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fatores de Tempo , Vitamina E/administração & dosagem , Vitamina E/uso terapêutico
16.
Mol Cell Biochem ; 241(1-2): 107-14, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12482032

RESUMO

In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents fructose-induced hypertension by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether dietary supplementation of vitamin E and vitamin C which are known to increase tissue glutathione, a storage form of cysteine, prevents this hypertension and its associated biochemical and histopathological changes. Starting at 7 weeks of age, animals were divided into four groups of six animals each and treated as follows: control group, normal diet and normal drinking water; fructose group, normal diet and 4% fructose in drinking water; fructose + vitamin E group, diet supplemented with vitamin E (34 mg/ kg feed) and 4% fructose in drinking water; fructose + vitamin C group, diet supplemented with vitamin C (1,000 mg/kg feed) and 4% fructose in drinking water. At 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugates were significantly higher in the fructose group. These animals also displayed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin E and C supplementation in fructose-treated WKY rats prevented the increase in systolic blood pressure by normalizing cytosolic [Ca2+]i and kidney and aortic aldehyde conjugates and preventing adverse renal vascular changes.


Assuntos
Ácido Ascórbico/administração & dosagem , Frutose/administração & dosagem , Hipertensão/induzido quimicamente , Vitamina E/administração & dosagem , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Peso Corporal , Cálcio/metabolismo , Comportamento de Ingestão de Líquido , Comportamento Alimentar , Hipertensão/prevenção & controle , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos WKY
17.
Nutr Metab Cardiovasc Dis ; 10(6): 339-46, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11302009

RESUMO

BACKGROUND AND AIMS: In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, alter membrane Ca2+ channels and increase cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents such hypertension by binding these aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of this work was to investigate whether dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound known to increase cysteine and glutathione, prevents this hypertension and its associated biochemical and histopathological changes. METHODS AND RESULTS: Starting at seven weeks of age, animals were divided into three groups of six animals each and treated as follows: control (normal diet and normal drinking water); fructose (normal diet and 4% fructose in drinking water); fructose + lipoic acid (diet supplemented with lipoic acid 500 mg/kg feed and 4% fructose in drinking water). After 14 weeks, systolic blood pressure, platelet [Ca2+]i, plasma glucose and insulin and kidney and aortic aldehyde conjugates were significantly higher in the fructose group. These also displayed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. CONCLUSION: Dietary alpha-lipoic acid supplementation in fructose-treated WKY rats may prevent their increase in systolic blood pressure by normalizing cytosolic [Ca2+], blood glucose and insulin, kidney and aortic aldehyde conjugates and preventing adverse renal vascular changes.


Assuntos
Hipertensão/prevenção & controle , Ácido Tióctico/administração & dosagem , Aldeídos/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Frutose/toxicidade , Hipertensão/sangue , Hipertensão/induzido quimicamente , Insulina , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ratos , Ratos Endogâmicos WKY , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico
18.
Mol Cell Biochem ; 181(1-2): 1-9, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9562236

RESUMO

Aldehydes are formed in tissues of humans and animals as intermediates of glucose and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals age 7 weeks were divided into three groups of 6 animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4% fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4% fructose in drinking water). After 11 weeks, systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose treated rats. NAC treatment prevented these changes. These results suggest that aldehydes may be the cause of fructose induced hypertension and elevated cytosolic free calcium.


Assuntos
Acetilcisteína/farmacologia , Aldeídos/análise , Frutose/farmacologia , Hipertensão/metabolismo , Animais , Plaquetas/química , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal , Cálcio/sangue , Dieta , Ingestão de Líquidos , Ingestão de Alimentos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Rim/química , Lipofuscina/análise , Tamanho do Órgão , Ratos , Ratos Endogâmicos WKY
19.
Mol Cell Biochem ; 200(1-2): 85-92, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10569187

RESUMO

Light to moderate drinking in humans lowers the risk of coronary heart disease and may lower blood pressure. We examined the effect of chronic low daily alcohol consumption on blood pressure, platelet cytosolic free calcium [Ca2+]i, tissue aldehyde conjugates and renal vascular changes in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). We also examined the effects of the same weekly amount of alcohol consumption over a one day period each week simulating weekend drinking in humans. Animals, age 7 weeks, were divided into six groups of six animals each and were treated as follows: WKY and SHR control, normal drinking water; WKY and SHR, 0.5% ethanol in drinking water; WKY and SHR, 3.5% ethanol in drinking water one day/week. After 14 weeks systolic blood pressure, platelet [Ca2+]i, liver, kidney and aortic aldehyde conjugates were significantly higher (p < 0.05) in untreated SHRs as compared to untreated WKYs. Daily 0.5% ethanol consumption in SHRs significantly (p < 0.05) attenuated these changes and also attenuated smooth muscle cell hyperplasia and narrowing of the lumen in small arteries and arterioles of the kidney. WKY rats treated with 0.5% ethanol had lower aldehyde conjugates without any significant effect on blood pressure and platelet [Ca2+]i as compared to WKY controls. Consumption of 3.5% ethanol one day/week did not affect blood pressure and associated changes in normotensive WKY rats or hypertensive SHRs as compared to their respective controls. These results suggest that chronic daily low ethanol intake lowers blood pressure in SHRs by lowering tissue aldehyde conjugates and cytosolic free calcium.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Etanol/administração & dosagem , Hipertensão/terapia , Consumo de Bebidas Alcoólicas/patologia , Aldeídos/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Distribuição Tecidual
20.
Mol Cell Biochem ; 200(1-2): 155-62, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10569195

RESUMO

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels, increasing cytosolic free calcium and blood pressure. N-acetyl cysteine normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. It is known that dietary vitamin B6 supplementation can increase the level of endogenous cysteine. Our objective was to investigate whether a dietary supplementation of vitamin B6 can prevent hypertension and associated changes in SHRs. Starting at 7 weeks of age, animals were divided into three groups of six animals each. Animals in WKY-control group and SHR-control group were given a normal vitamin B6 diet; and SHR-vitamin B6 group, a high vitamin B6 diet (20 times the recommended dietary intake; RDA) for the next 14 weeks. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls compared to WKY controls. These animals also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation attenuated the increase in systolic blood pressure, tissue aldehyde conjugates and associated changes. These results further support the hypothesis that aldehydes are involved in increased systolic blood pressure in SHRs and suggest that vitamin B6 supplementation may be an effective antihypertensive.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Piridoxina/administração & dosagem , Aldeídos/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Plaquetas/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cálcio/sangue , Hipertensão/patologia , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
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