RESUMO
BACKGROUND: Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms' tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation. METHODS: Male spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups. RESULTS: The relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4. CONCLUSIONS: Our results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension.
Assuntos
Hipertensão/metabolismo , Rim/metabolismo , Mitocôndrias/ultraestrutura , Proteínas WT1/metabolismo , Animais , Animais Recém-Nascidos , Apoptose , Pressão Sanguínea , Peso Corporal , Fibrose , Proteínas de Choque Térmico HSP70/metabolismo , Hipertensão/patologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Rim/patologia , Córtex Renal/metabolismo , Masculino , Microscopia Confocal , Microscopia Eletrônica , Microscopia de Fluorescência , Tamanho do Órgão , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores de Calcitriol/metabolismoRESUMO
We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between "primary" (active ingredient) and "secondary" patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate "older" therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents.
Assuntos
Química Farmacêutica , Indústria Farmacêutica , Patentes como Assunto , Preparações Farmacêuticas , Chile , HumanosRESUMO
The invasive Pomacea canaliculata estivates during periods of drought and should cope with harmful effects of reoxygenation during arousal. We studied thiobarbituric acid reactive substances (TBARS), enzymatic (superoxide dismutase, SOD and catalase, CAT) and non-enzymatic antioxidants (uric acid and reduced glutathione), and heat shock protein expression (Hsc70, Hsp70 and Hsp90) in (1) active control snails, (2) snails after 45 days of estivation, and (3) aroused snails 20 min and (4) 24 h after water exposure, in midgut gland, kidney and foot. Both kidney and foot (but not the midgut gland) showed a TBARS increase during estivation and a decrease after arousal. Tissue SOD and CAT did not change in any experimental groups. Uric acid increased during estivation in all tissues, and it decreased after arousal in the kidney. Allantoin, the oxidation product of uric acid, remained constant in the midgut gland but it decreased in the kidney until 20 min after arousal; however, allantoin levels rose in both kidney and foot 24 h after arousal. Reduced glutathione decreased during estivation and arousal, in both midgut gland and kidney, and it remained constant in the foot. Hsc70 and Hsp70 kidney levels were stable during the activity-estivation cycle and Hsp90 expression decreases during estivation and recovers in the early arousal. In foot, the expression of Hsp70 and Hsp90 was high during activity and estivation periods and disminished after arousal. Results indicate that a panoply of antioxidant and molecular chaperone defences may be involved during the activity-estivation cycle in this freshwater gastropod.
Assuntos
Antioxidantes/metabolismo , Nível de Alerta/fisiologia , Estivação/imunologia , Caracois Helix/imunologia , Chaperonas Moleculares/metabolismo , Alantoína/metabolismo , Animais , Glutationa , Proteínas de Choque Térmico/metabolismo , Caracois Helix/enzimologia , Rim/citologia , Rim/metabolismo , Peroxidação de Lipídeos , Malus , Modelos Biológicos , América do Sul , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ácido Úrico/metabolismoRESUMO
This study sought to find a correlation between the prosthetic status and TMD and between the prosthetic status and self-perception of oral health in a Brazilian elderly population (n = 400). Prosthetic status was recorded in clinical examinations, and TMD was determined by applying the Helkimo index. Self-perception of oral health was evaluated based on the Geriatric Oral Health Assessment Index (GOHAI). The most prevalent prosthetic status was edentulous using complete dentures (47.5%). Absence of subjective TMD symptoms was found in 69.5%, and of clinical TMD signs in 38.3% of the population. The average GOHAI score was 33.02 +/- 2.85. A correlation was found between prosthetic status and TMD subjective symptoms (P = 0.017), but prosthetic status and TMD objective signs were uncorrelated (P = 0.061). Prosthetic status and self-perception of oral health were positively correlated (P = 0.001).
Assuntos
Prótese Dentária/psicologia , Arcada Edêntula/complicações , Saúde Bucal , Qualidade de Vida , Transtornos da Articulação Temporomandibular/etiologia , Idoso , Brasil , Distribuição de Qui-Quadrado , Prótese Dentária/efeitos adversos , Autoavaliação Diagnóstica , Feminino , Avaliação Geriátrica , Humanos , Vida Independente , Institucionalização , Arcada Edêntula/psicologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Perfil de Impacto da Doença , Estatísticas não Paramétricas , Transtornos da Articulação Temporomandibular/psicologiaRESUMO
The physiological ability to estivate is relevant for the maintenance of population size in the invasive Pomacea canaliculata. However, tissue reoxygenation during arousal from estivation poses the problem of acute oxidative stress. Uric acid is a potent antioxidant in several systems and it is stored in specialized tissues of P. canaliculata. Changes in tissue concentration of thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were measured during estivation and arousal in P. canaliculata. Both TBARS and uric acid increased two-fold during 45 days estivation, probably as a consequence of concomitant oxyradical production during uric acid synthesis by xanthine oxidase. However, after arousal was induced, uric acid and TBARS dropped to or near baseline levels within 20 min and remained low up to 24h after arousal induction, while the urate oxidation product allantoin continuously rose to a maximum at 24h after induction, indicating the participation of uric acid as an antioxidant during reoxygenation. Neither uric acid nor allantoin was detected in the excreta during this 24h period. Urate oxidase activity was also found in organs of active snails, but activity shut down during estivation and only a partial and sustained recovery was observed in the midgut gland.
Assuntos
Antioxidantes/metabolismo , Estivação , Caramujos/metabolismo , Ácido Úrico/metabolismo , Alantoína/metabolismo , Animais , Comportamento Animal , Feminino , Peroxidação de Lipídeos , Masculino , Caramujos/enzimologia , Caramujos/fisiologia , Urato Oxidase/metabolismoRESUMO
RATIONALE AND OBJECTIVES: Considering the controversy in the literature regarding several aspects of temporomandibular dysfunction (TMD) in elderly populations and the absence of reliable data on elderly Brazilians in this field, this study consisted of an evaluation of TMD prevalence and the self-perception of oral health among institutionalised and community-dwelling elderly in São José dos Campos, Brazil. METHODS: Two hundred and fifteen community-dwelling and 185 institutionalised elderly people were evaluated by the Helkimo anamnestic (Ai) and clinical dysfunction (Di) indices and answered a questionnaire using the Geriatric Oral Health Assessment Index (GOHAI). RESULTS: The major prevalence of TMD symptoms was for the Ai0 (symptom-free) group (69.5%), while the major prevalence of clinical signs was for the DiI (mild) group (56%). Women presented a higher AiII classification than men (chi(2) test, p = 0.049). Community-dwelling elderly presented a significantly lower Ai0 classification than the institutionalised ones (Two ratios equality test, p < 0.001). There was no relationship between the institutionalised status and the clinical dysfunction index for Di0 and DiIII classification (Two ratios equality test, p = 0.194 and 0.535 respectively). The institutionalised elderly presented greater (One-way ANOVA = 0.005) self-perception of oral health (33.45) than did the community-dwelling group (32.66). There were only weak Pearson's correlations among the anamnestic (-33.0%) or clinical (-14.7%) findings by the TMD and GOHAI indices. Symptom-free (Ai0) institutionalised elderly presented better scores in all GOHAI dimensions and elderly representing an absence of clinical TMD signs (Di0) presented higher GOHAI physical dimension scores in both groups. CONCLUSIONS: The prevalence of TMD symptoms among this sample of elderly individuals was relatively low, self-perception of oral health was reasonable and a weak, inverse correlation was found between TMD signs and symptoms and elderly self-perception of oral health measured by the GOHAI index.
Assuntos
Avaliação Geriátrica/estatística & dados numéricos , Institucionalização/estatística & dados numéricos , Transtornos da Articulação Temporomandibular/epidemiologia , Atividades Cotidianas , Idoso , Atitude Frente a Saúde , Brasil/epidemiologia , Deglutição/fisiologia , Ingestão de Alimentos/fisiologia , Estética Dentária , Feminino , Humanos , Masculino , Mastigação/fisiologia , Pessoa de Meia-Idade , Saúde Bucal , Prevalência , Autoimagem , Fatores Sexuais , Ajustamento Social , Fala/fisiologiaRESUMO
OBJECTIVES: To determine and compare the antioxidant power, cellular damage by lipidic peroxidation, and membrane damage in normal patients and patients with prostate cancer, so determining the antitumoral capacity. METHODS: The study population included 19 patients with elevated total PSA, greater than 4 ng/ml, with a minimum of 10 ultrasound guided transrectal biopsies, and 10 normal subjects as control group. In all cases, medical history, rectal digital examination, PSA determination and routine analyses were performed in addition to spectrophotometric tests to measure the antioxidant power. Membrane damage was measured by determination of malonyldialdehyde (MDA) and cellular damage by glutathione peroxidase. RESULTS: From a total of 19 cases: 6 (31.5%) presented prostate cancer (4 Gleason 7; 1 Gleason 6 and 1 Gleason 8); 8 presented histological benign prostatic hyperplasia with a component of chronic prostatitis; 3 patients prostatic hyperplasia and glandular atrophy; and 2 cases isolated benign prostatic hyperplasia. All 10 control patients presented values within normal range in all determinations, whereas study patients showed antioxidant power < 1.3 mmol/l in 13 cases; higher than 1.77 mmol/l in 4 and normal values in 2. MDA was elevated in 15 patients and normal in 4, all of them without histological chronic prostatitis. Four of the patients with prostate cancer presented a diminished antioxidant power below 0.90, with a relationship with glandular architecture, because those with Gleason 8 and 7 did not exceed 0.58 mmol/l. Two patients with prostate cancer with a lower Gleason score presented normal minimal values. CONCLUSIONS: Patients with prostate cancer or reactive processes, such as chronic prostatitis or atrophic prostatitis, present a decreased antioxidant power and an increase of lipidic peroxidation.
Assuntos
Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Antioxidantes , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Neoplasias da Próstata/etiologiaRESUMO
mujeres que cursan su segundo trimestre de embarazo, con bocas activas (gingivitis), pueden ejercer efectos antioxidantes sobre la lipoperoxidación que ocurre al ingerir un alimento lipídico (aceite insaturado).El estudio se realizó en 42 mujeres, 22 embarazadas en el segundo trimestre y 20 no embarazadas, a todas se les hizo un análisis bioquímico de saliva antes y después de realizar tratamiento odontológico para control de la placa bacteriana. Los resultados obtenidos nos indican que hay una producción de especies reactivas del oxígeno, que se manifiesta al actuar sobre el aceite y producir malonildialdehído, además la superóxido dismutasa en mayor grado y la glutarión peroxidasa ejercen sus efectos protectores; el ácido úrico parece ser el mejor antioxidante salival y es en el segundo trimestre de la gestación donde se produciren las variaciones más significativas, siendo evidente que el tratamiento odontológico mejora el desbalance oxidativo, encontrado en bocas con gingivitis...
Assuntos
Feminino , Gravidez , Gengivite , Peróxidos Lipídicos , Segundo Trimestre da Gravidez , Argentina , Odontologia , Gestantes , SalivaRESUMO
Día a día aparecen más enfermedades relacionadas con los radicales libres del oxígeno y el metabolismo oxidativo. En la mayoría de los casos no se sabe si son causa o efecto de un proceso determinado, pero sigue siendo valioso saber qué moléculas pueden bloquear o prevenir las reacciones de iniciación de los radicales libres, actuando como antioxidantes, e interpretar dónde están localizadas y cuál es su mecanismo de acción, lo que permitiría revertir las lesiones citotóxicas encontradas en los seres humanos.- En el presente trabajo, realizado con saliva total de 95 niños de una zona rural de la provincia de Mendoza (Argentina), los resultados obtenidos permiten confirmar que en los procesos cariosos existe un estrés radicalario, aparición de xantina-oxidasa que produce radicales libres y disminución de la superóxido dismutasa que trata de frenarlos.-Este estrés radicalario o desbalance oxidativo puede ser corregido por mecanismos endógenos de defensa (vitamina C, glutatión) y tratamiento adecuado de las caries...