5-AMINOLEVULINIC ACID-INDUCED ALTERATIONS OF OXIDATIVE-METABOLISM IN SEDENTARY AND EXERCISE-TRAINED RATS

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.

Surface dental enamel lead levels and antisocial behavior in Brazilian adolescents

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reajustando o limite de tolerância biológica aplicado à plumbemia no Brasil

Foram alocados aleatoriamente vinte trabalhadores expostos ocupacionalmente ao chumbo em uma indústria de acumuladores elétricos de médio porte, no interior do Estado de São Paulo, os quais apresentavam plumbemia e excreção urinária do ácido delta-aminolevulínico, nos últimos dois anos, sempre menores que 60 µg/dL e 10 mg/L, respectivamente. Os trabalhadores foram submetidos a eletroneurografia do nervo radial direito e a dosagem de plumbemia. Com estas medidas ajustou-se um modelo de regressão linear simples de primeira ordem, tendo como variável dependente a velocidade de condução e como variável independente a plumbemia. Analisando-se a regressão ajustada, infere-se que o valor preditivo negativo do limite de tolerância biológica brasileiro aplicado à plumbemia seja de apenas 0,63. O estudo sugere que o valor do referido limite de tolerância deva ser reduzido do atual valor de 60 µg/dL para 32 µg/dL, para ter um valor preditivo negativo de 0,99.

Distúrbios neurológicos em trabalhadores com baixos níveis de chumbo no sangue. I: Neuropatia periférica

This is a cross-sectional study with a randomized choice of individuals aiming at studying the validity of the Brazilian biological exposure limits applied to lead level in the blood (PbB) and delta-aminolevulinic acid in the urine (ALAU), which are 60 μg/dl and 10 mg/g.creat., respectively. For this purpose, twenty workers, whose PbB and ALAU values have been below these limits over the past two years, were selected at random at a battery production plant in the State of S. Paulo, Brazil. The workers were submitted to a peripheral nerve conduction study. The results were compared with those obtained for workers of a control group also chosen at random. The lead workers showed a decrease in the velocity conduction of the radial nerves. Comparing this group with a randomized control group, a significant difference was observed (p-value = 0.0067). The results suggest that the Brazilian biological exposure limits above should be rearranged.

Distúrbios neurológicos em trabalhadores com baixos níveis de chumbo no sangue. II-Disfunc̈ões neurocomportamentais

This is a cross-sectional study with a randomized choice of individuals aiming at studying the validity of the Brazilian biological exposure limits applied to lead level in the blood (PbB) and delta-aminolevulinic acid in the urine (ALAU), which are 60 μ/dl and 10 mg/g.creat., respectively. Thus, twenty workers, whose PbB and ALAU values have been below these limits over the past two years, were selected at random at a battery plant in the State of S. Paulo, Brazil. The workers were submitted to a variation of the WHO Neurobehavioral Core Test Battery. The results were compared with those obtained for workers of a control group also chosen at random. The lead workers showed memory, mood and motor coordination disorders. Comparing these results with those obtained from the control group, a significant difference was observed (p-value < 0.02). The results indicate that the Brazilian biological exposure limits above should be reconsidered.

Can trifluoperazine protect mitochondria against reactive oxygen species-induced damage?

Trifluoperazine (TFP) (35 μM) prevents mitochondrial transmembrane potential (ΔΨ) collapse and swelling induced by 10 μM Ca2+ plus oxyradicals generated from δ-aminolevulinic acid autoxidation. In contrast with EGTA, TFP cannot restore the totally collapsed ΔΨ. So, TFP might not remove Ca2+ from its 'harmful site', but could impair the ROS-driven cross-linking between membrane -SH proteins. Our data are correlated with the protective uses of TFP against oxidative processes promoted by oxyradicals plus Ca2+.

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise comparativa entre terapia fotodinâmica com ácido 5-aminolevulínico versus crioterapia no tratamento da queratose actínica: estudo prospectivo randonizado

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Tratamento de queratose actínica disseminada através da terapia fotodinâmica

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Queratoses actínias disseminadas de membros superiores: comparação da terapia fotodinâmica com ácido aminolevulínico 15%¨e metil aminolevulínico 15 % através do protótico kerato PDT

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Assessment of ALA-induced PpIX production in porcine skin pretreated with microneedles

Photodynamic therapy (PDT) is used for skin treatments of premalignant and cancer lesions and recognized as a non-invasive technique that combines tissue photosensitization and subsequent exposure to light to induce cell death. However, it is limited to the treatment of superficial lesions, mainly due to the low cream penetration. Therefore, the improvement of transdermal distribution of aminolevulinic acid (ALA) is needed. In this study, the kinetics and homogeneity of production of ALA-induced PpIX after the skin pre-treatment with microneedles rollers of 0.5, 1.0 and 1.5 mm length were investigated. An improvement in homogeneity and production of PpIX was shown in a porcine model. Widefield fluorescence imaging three hours after the topical application of ALA-cream in the combined treatment with microeedles rollers.