RESUMEN
An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder. Aim of our research is to investigate the possible role of heavy metals in the severity of the disease. In this study, by the use of plasma mass (ICP-MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al, Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and controls; moreover we divided the patients in two groups for disease severity and analyzed the difference among the groups, in order to study a possible involvement of metals in the severity of the damage. Our results suggest a protective role of Selenium, involved in protective antioxidant mechanisms, and a risk factor in the case of presence of Lead in blood. The levels of the other metals are not easy to interpret, because these may be due to life style and for essential metals a consequence of the disease condition, not a cause.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Exposición a Riesgos Ambientales/estadística & datos numéricos , Oligoelementos/sangre , Adulto , Esclerosis Amiotrófica Lateral/epidemiología , Femenino , Cabello , Humanos , Masculino , Mercurio/metabolismo , Metales Pesados/metabolismo , Persona de Mediana Edad , Selenio/metabolismoRESUMEN
BACKGROUND: Hepatitis C virus infection and interferon treatment have shown to be risk factors for sleep disorder health-related quality of life. AIM: To determine whether the effects of resveratrol on sleep disorders were associated with different tests in subjects with chronic hepatitis C treated with Peg-IFN-α and RBV. PATIENTS AND METHODS: In this prospective, randomized, placebo controlled, double blind clinical trial, 30 subjects (Group A) with chronic hepatitis received Pegylated-Interferon-α2b (1.5 mg/kg per week), Ribavirin and placebo (N-acetylcysteine 600 mg and lactoferrin 23.6 g), while 30 subjects (Group B) received the same dosage of Pegylated-Interferon-α2b, Ribavirin and association of N-acetylcysteine 600 mg, lactoferrin 23.6 g and Resveratrol 19.8 mg for 12 months. All subjects underwent laboratory exams and questionnaires to evaluate mood and sleep disorders (General Health Questionnaire (GHQ), Profile of Mood States (POMS), Pittsburgh Sleep Quality Inventory (PSQI), Epworth Sleepiness Scale (ESS)). RESULTS: The comparison between Group A and Group B showed significant differences after six months in C-reactive protein (p < 0.0001); after 12 months in aspartate aminotransferase (AST) (p < 0.0001) Viremia (p < 0.0001), HAI (p < 0.0012) and C-reactive protein (p < 0.0001); and at follow up in AST (p < 0.0001), Viremia (p < 0.0026) and C-reactive protein (p < 0.0001). Significant differences were observed after 12 month and follow-up in General Health Questionnaire, after 1, 6, 12 and follow-up in Profile of Mood States, after 6, 12, follow-up in Pittsburgh Sleep Quality Inventory and Epworth Sleepiness Scale. CONCLUSIONS: Supplementation with Resveratrol decreased General Health Questionnaire score and reduced sleep disorders in patients treated with Peg-IFN-α and RBV.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Trastornos del Sueño-Vigilia/prevención & control , Estilbenos/uso terapéutico , Acetilcisteína/uso terapéutico , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Glucemia/metabolismo , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Interferón alfa-2 , Lactoferrina/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Proteínas Recombinantes/uso terapéutico , Resveratrol , Encuestas y CuestionariosRESUMEN
Mechanisms for the onset of diabetes and the development of diabetic complications remain under extensive investigations. One of these mechanisms is abnormal homeostasis of metals, as either deficiency or excess of metals, can contribute to certain diabetic outcomes. Therefore, this paper will report the blood levels of chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), and zinc (Zn) in subjects with type 1 diabetes (n = 192, mean age 48.8 years, mean disease duration 20.6 years), type 2 diabetes (n = 68, mean age 68.4 years, mean disease duration 10.2 years), and in control subjects (n = 59, mean age 57.2 years), and discuss the results indicating their possible role in diabetes. The metal concentrations were measured by sector field inductively coupled plasma mass spectrometry after microwave-induced acid digestion of blood samples. The accuracy was checked using a blood-based certified reference material, and recoveries of all elements were in the range of 92-101 % of certified values. Type 1 diabetes was found to be associated with Cr (p = 0.02), Mn (p < 0.001), Ni (p < 0.001), Pb (p = 0.02), and Zn (p < 0.001) deficiency, and type 2 diabetes with Cr (p = 0.014), Mn (p < 0.001), and Ni (p < 0.001) deficiency. These deficiencies were appreciated also subdividing the understudied patients for gender and age groups. Furthermore, in type 1 diabetes, there was a positive correlation between Pb and age (p < 0.001, ρ = 0.400) and Pb and BMI (p < 0.001, ρ = 0.309), while a negative correlation between Fe and age (p = 0.002, ρ = -0.218). In type 2 diabetes, there was a negative correlation between Fe and age (p = 0.017, ρ = -0.294) and Fe and BMI (p = 0.026, ρ = -0.301). Thus, these elements may play a role in both forms of diabetes and combined mineral supplementations could have beneficial effects.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Metales/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The limited ability of conventional therapies to achieve the long-term survival of metastatic lung and colon cancer patients suggests the need for new treatment options. In this respect, genes encoding cytotoxic proteins have been proposed as a new strategy to enhance the activity of drugs, and combined therapies involving such genes and classical antitumoral drugs have been studied intensively. The E gene from phiX174 encodes a membrane protein with a toxic domain that leads to a decrease in tumour cell growth rates. Therefore, in order to improve the anti-tumour effects of currently used chemotherapeutic drugs on cancer cells, we investigated the association of the E suicide gene with these antineoplastic drugs. The E gene has antitumoral effects in both lung and colon cancer cells. In addition, expression of this gene induces ultrastructural changes in lung cancer transfected cells (A-549), although the significance of these changes remains unknown. The effect of combined therapy (gene and cytotoxic therapy) enhances the inhibition of tumour cell proliferation in comparison to single treatments. Indeed, our in vitro results indicate that an experimental therapeutic strategy based on this combination of E gene therapy and cytotoxic drugs may result in a new treatment strategy for patients with advanced lung and colon cancer.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis , Bacteriófagos/genética , Neoplasias del Colon/terapia , Neoplasias Pulmonares/terapia , Proteínas Virales/toxicidad , Apoptosis/efectos de los fármacos , Bacteriófagos/metabolismo , Terapia Biológica , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/fisiopatología , Terapia Combinada , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatología , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
The reference ranges for blood Cu, Mn, Se and Zn of 215 adult subjects non-occupationally exposed and living in the Nuoro province (Sardinia, insular Italy) were assessed. Metals were determined by sector field inductively coupled plasma mass spectrometry after microwave-assisted acid digestion of blood. The blood reference ranges estimated as P5-P95 percentiles (geometric mean, GM) were 776-1495µg/L (1036µg/L) for Cu; 4.73-17.0µg/L (8.91µg/L) for Mn; 106-185µg/L (140µg/L) for Se and 4686-8585µg/L (6418µg/L) for Zn. These results were then stratified for sex, age, alcohol consumption, smoking habit and living area. The GM value of Cu was significantly higher in females (1127µg/L) than in males (957µg/L). Age, alcohol intake, smoking habit and residential area did not influence blood Cu. The GM of Mn was significantly higher in females (9.98µg/L) respect to males (8.01µg/L) and in drinkers (9.67µg/L) compared to non-drinkers (8.38µg/L). The other variables did not change the Mn data. Selenium concentrations did not differ significantly as a function of individuals factors. With reference to Zn, males had GM of 6804µg/L and females of 6031µg/L, and more blood Zn was found in subjects consuming alcohol (6618µg/L) respect to abstainers (6155µg/L). In addition, blood Zn was not affected by age, smoking habit and place of living.