RESUMO
Ageing is characterized by a progressive loss of complexity, which is an essential condition for making the organism capable of keeping homeostasis. Thus, senile loss of complexity makes old individuals frail: a syndrome characterized by the presence of shrinking (sarcopenia), weakness, poor endurance and energy, slowness, and low physical activity. Moreover, renal ageing progressively leads to a glomerular filtration rate (GFR) reduction, one of the main pharmacokinetic senile changes, which is not detectable by simply evaluating serum urea or creatinine values but measuring or calculating patient's GFR. Finally, current epidemiology has documented that detrimental social-behavioral factors such as low education level, poor financial-resource, depression, and isolation, also influence the onset and progression of chronic diseases, and even overall mortality, particularly in the elderly. Thus, we propose that these 3 variables: frailty phenotype, senile GFR, and detrimental social-behavioral factors, should be considered at time of prescribing drugs or medical procedures in the elderly. Additionally, they should also be considered for following patient's response to prescribed therapies in elderly patients suffering from chronic diseases (diabetes mellitus, chronic kidney disease, etc.), or on organ replacement treatments (dialysis and transplantation).
Assuntos
Envelhecimento , Doença Crônica/tratamento farmacológico , Progressão da Doença , Idoso Fragilizado/psicologia , Fatores Socioeconômicos , Idoso de 80 Anos ou mais , Depressão/fisiopatologia , Escolaridade , Taxa de Filtração Glomerular/fisiologia , Humanos , Isolamento SocialRESUMO
INTRODUCTION: Despite increasing use in clinical practice, an estimated glomerular filtration rate value (eGFR) of <60 ml/min/1.73 m2 does not necessarily indicate the existence of chronic renal insufficiency (CRI) and this may lead to an over-estimate of CRI particularly in persons seventy years or older. AIM: To find a screening test able to differentiate CRI from the decrease in GFR normally associated with the renal ageing process. METHODS: Medical information of 487 individuals of both sexes aged 16-102 was obtained from nephrologists, internal medicine physicians, cardiologists, geriatricians, family and nuclear medicine doctors from Argentina, Portugal and Spain. Data were assessed and statistically analysed using logistic regression techniques. From the discriminative variables it was derived the HUGE formula. RESULTS: A formula including haematocrit , blood urea, and gender (HUGE), diagnoses CRI regardless of the variables of age, blood creatinine, creatinine clearance, or other eGFR. The HUGE formula is: L = 2.505458 - (0.264418 x Hematocrit) + (0.118100 x Urea) [+ 1.383960 if male]. If L is a negative number the individual does not have CRI; if L is a positive number, CRI is present. Our data demonstrate that the HUGE formula is more reliable than MDRD and CKD-EPI, particularly in persons aged over 70. CONCLUSIONS: Our HUGE screening formula offers a straightforward, easily available and inexpensive method for differentiating between CRI and eGFR < 60 ml/min/1.73 m2 that will prevent a considerable number of aged healthy persons, as much as 1.700.000 in Spain and 2.600.000 in U.K., to be excluded from clinical assays or treatments contraindicated in CRI.
Assuntos
Hematócrito , Testes de Função Renal/métodos , Programas de Rastreamento/métodos , Insuficiência Renal Crônica/diagnóstico , Ureia/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Masculino , Matemática , Pessoa de Meia-Idade , Portugal , Insuficiência Renal Crônica/sangue , Reprodutibilidade dos Testes , Fatores Sexuais , Espanha , Adulto JovemRESUMO
El serogrupo Ballum de Leptospira constituye en la actualidad la primera causa de leptospirosis humana en Cuba. Vacunas de células enteras químicamente inactivadas fueron formuladas a partir de dos cepas clínicas de Leptospira interrogans serogrupo Ballum empleando como adyuvante hidróxido de aluminio. Los niveles de aglutininas inducidos en hamsters por una u otra preparación vacunal fueron estimados mediante aglutinación microscópica y la actividad IgG específica fue cuantificada mediante ELISA. La capacidad de protección homóloga y heteróloga contra la infección letal y subletal se determinó mediante el desafío con 100 y 10 000 DL50 de cinco cepas virulentas pertenecientes a los serogrupos Ballum, Canicola, Icterohaemorrhagiae y Pomona. Las evaluaciones realizadas demostraron que ambas vacunas fueron inmunogénicas e indujeron una completa protección homóloga en el modelo animal empleado. La protección cruzada frente a serogrupos heterólogos solo fue significativa en una de las preparaciones monovalentes frente al desafío con 100 DL50 de Canicola. Como resultado de este estudio se pudo comprobar la alta inmunogenicidad y capacidad protectora en hamsters de vacunas monovalentes de células enteras formuladas a partir de dos cepas candidatas vacunales del serogrupo de Leptospira de mayor circulación en humanos en Cuba no incluido en la vacuna actualmente disponible.
Leptospira serogroup Ballum is at present the first cause of human leptospirosis in Cuba. Killed whole-cell vaccines were formulated with two clinical isolates of Leptospira interrogans serogroup Ballum using aluminum hydroxide as adjuvant. Agglutinins levels induced by each vaccine in hamsters were estimated by microscopic agglutination test and specific IgG activities were quantified by a whole cell-based enzyme-linked immunosorbent assay. Homologous and cross protective capacity against lethal and sublethal infection were determined in vaccinated animals by challenge with 100 and 10 000 LD50 of five virulent strains belonging to serogroups Ballum, Canicola, Icterohaemorrhagiae and Pomona. Both monovalent serogroup Ballum vaccines were immunogenic and induced complete homologous protection in the animal model. Cross-protection was only significant in one of the two vaccines against challenge with 100 LD50 of serogroup Canicola. The results of this study demonstrate the high immunogenicity and protective capacity in hamsters of whole-cell monovalent vaccines formulated with two vaccine candidate strains belonging to the most prevalent serogroup of Leptospira in Cuba.
Assuntos
Animais , Cricetinae , Vacinas Bacterianas/imunologia , Leptospira interrogans/imunologia , Leptospirose/prevenção & controle , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Avaliação Pré-Clínica de Medicamentos , Imunoglobulina G/sangue , Leptospira interrogans serovar canicola/imunologia , Leptospira interrogans serovar icterohaemorrhagiae/imunologia , Leptospira interrogans serovar pomona/imunologia , Mesocricetus , VacinaçãoRESUMO
Leptospira serogroup Ballum is at present the first cause of human leptospirosis in Cuba. Killed whole-cell vaccines were formulated with two clinical isolates of Leptospira interrogans serogroup Ballum using aluminum hydroxide as adjuvant. Agglutinins levels induced by each vaccine in hamsters were estimated by microscopic agglutination test and specific IgG activities were quantified by a whole cell-based enzyme-linked immunosorbent assay. Homologous and cross protective capacity against lethal and sublethal infection were determined in vaccinated animals by challenge with 100 and 10,000 LD50 of five virulent strains belonging to serogroups Ballum, Canicola, Icterohaemorrhagiae and Pomona. Both monovalent serogroup Ballum vaccines were immunogenic and induced complete homologous protection in the animal model. Cross-protection was only significant in one of the two vaccines against challenge with 100 LD50 of serogroup Canicola. The results of this study demonstrate the high immunogenicity and protective capacity in hamsters of whole-cell monovalent vaccines formulated with two vaccine candidate strains belonging to the most prevalent serogroup of Leptospira in Cuba.
Assuntos
Vacinas Bacterianas/imunologia , Leptospira interrogans/imunologia , Leptospirose/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Imunoglobulina G/sangue , Leptospira interrogans serovar canicola/imunologia , Leptospira interrogans serovar icterohaemorrhagiae/imunologia , Leptospira interrogans serovar pomona/imunologia , Mesocricetus , VacinaçãoRESUMO
Leptospira serogroup Ballum is at present the first cause of human leptospirosis in Cuba. Killed whole-cell vaccines were formulated with two clinical isolates of Leptospira interrogans serogroup Ballum using aluminum hydroxide as adjuvant. Agglutinins levels induced by each vaccine in hamsters were estimated by microscopic agglutination test and specific IgG activities were quantified by a whole cell-based enzyme-linked immunosorbent assay. Homologous and cross protective capacity against lethal and sublethal infection were determined in vaccinated animals by challenge with 100 and 10,000 LD50 of five virulent strains belonging to serogroups Ballum, Canicola, Icterohaemorrhagiae and Pomona. Both monovalent serogroup Ballum vaccines were immunogenic and induced complete homologous protection in the animal model. Cross-protection was only significant in one of the two vaccines against challenge with 100 LD50 of serogroup Canicola. The results of this study demonstrate the high immunogenicity and protective capacity in hamsters of whole-cell monovalent vaccines formulated with two vaccine candidate strains belonging to the most prevalent serogroup of Leptospira in Cuba.
RESUMO
Some evidence on the possible use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to elicit antibodies against smooth- or rough-type bacterial lipopolysaccharides (LPS) is shown. Gel-separated LPS were negatively stained with zinc-imidazole to precisely localize the bands of interest under fully reversible conditions. Then the bands of interest were excised and the resulting gel slices washed in a solution of a zinc-complexing agent (e.g., 100 mM EDTA), after which they were extruded through a metal sieve of 32 microm average size contained in a 1 mL syringe, to generate homogeneous gel microparticles. The LPS-containing gel slurries were used directly to immunize female BALB/c mice. Using this procedure, positive mouse polyclonal antibody responses against gel-purified smooth- or rough-LPS forms from Escherichia coli K-235 or Bordetella pertussis were elicited, as tested by a dot-immunoblotting assay. Our results may encourage the use of SDS-PAGE-micropurified LPS to develop optimized immunization procedures for the generation of specific antibodies against LPS bands of defined sizes, and therefore they constitute an intermediate step toward that aim.