Flagellar beating forces of human spermatozoa with different motility behaviors.

BACKGROUND: One of the causes of male infertility is associated with altered spermatozoa motility. These sperm features are frequently analyzed by image-based approaches, which, despite allowing the acquisition of crucial parameters to assess sperm motility, they are unable to provide details regarding the flagellar beating forces, which have been neglected until now. RESULTS: In this work we exploit Fluidic Force Microscopy to investigate and quantify the forces associated with the flagellar beating frequencies of human spermatozoa. The analysis is performed on two groups divided according to the progressive motility of semen samples, as identified by standard clinical protocols. In the first group, 100% of the spermatozoa swim linearly (100% progressive motility), while, in the other, spermatozoa show both linear and circular motility (identified as 80 - 20% progressive motility). Significant differences in flagellar beating forces between spermatozoa from semen sample with different progressive motility are observed. Particularly, linear motile spermatozoa exhibit forces higher than those with a circular movement. CONCLUSIONS: This research can increase our understanding of sperm motility and the role of mechanics in fertilization, which could help us unveil some of the causes of idiopathic male infertility.

FTIR Spectroscopy to Reveal Lipid and Protein Changes Induced on Sperm by Capacitation: Bases for an Improvement of Sample Selection in ART.

Although being a crucial step for Assisted Reproduction Technologies (ART) success, to date sperm selection is based only on morphology, motility and concentration characteristics. Considering the many possible alterations, there is a great need for analytical approaches allowing more effective sperm selections. The use of Fourier Transform Infrared (FTIR) may represent an interesting possibility, being able to reveal many macromolecular changes in a single measurement in a nondestructive way. As a proof of concept, in this observational study, we used a FTIR approach to reveal features related to sperm quality and chemical changes promoted by in vitro capacitation. We found indication that α-helix content is increased in capacitated sperm, while high percentages of the ß-structures seem to correlate to poor-quality spermatozoa. The most interesting observation was related to the lipid composition, when measured as CH2/CH3 vibrations (ratio 2853/2870), which resulted in being strongly influenced by capacitation and well correlated with sperm motility. Interestingly, this ratio is higher than 1 in infertile samples, suggesting that motility is related to sperm membranes stiffness and lipid composition. Although further analyses are requested, our results support the concept that FTIR can be proposed as a new smart diagnostic tool for semen quality assessment in ART.

Ultra-structural analysis of human spermatozoa by aperture scanning near-field optical microscopy.

Scanning near-field optical microscopy (SNOM) represents a potential candidate for investigation of ultrastructure in human spermatozoa. It is a noninvasive optical technique that offers two main advantages: minimal sample preparation and simultaneous topographical and optical images acquisition with a spatial resolution beyond the diffraction limit. This enables the combination of surface characterization and information from the inner cellular organization in a single acquisition providing an immediate and comprehensive analysis of the cellular portions. In this work spermatozoa are immobilized on poly-L-lysine coated coverslips, fixed according to a standard protocol and imaged by aperture-SNOM in air. In the SNOM images, all peculiar sperm portions show well-resolved optical features, which exhibit good similarities with the structures revealed in transmission electron microscopy images, as compared with literature data. The optical features of anomalous spermatozoa are clearly different as respect with those observed for healthy ones. This analysis reveals the potentialities of SNOM and opens to its application to high-resolution analysis of sperm morphological alterations, which might be relevant in reproductive medicine.

Exercise and non-exercise aerobic power prediction models using six-minute walk test / Equações de predição da potência aeróbica usando o teste de caminhada de seis minutos

BACKGROUND AND OBJECTIVE: A simple, low-cost approach commonly used to objectively analyze the cardiorespiratory fitness of individuals with different health conditions is the six-minute walk test (6-MWT). Our objective was to develop peak aerobic power prediction using the six-minute walk test in healthy older men. METHODS: We measured body composition (body mass [BM], body mass index [BMI], fat percentage [FAT]) and peak aerobic power breath-by-breath during cardiopulmonary exercise testing (CPET [velocity, heart rate [HR] and VO2 at the anaerobic threshold and peak]) and a 6-MWT (distance [D], weight by distance [WxD], HR and oxygen consumption [VO2] at peak) in 76 healthy older men aged 65 to 80 years (69.1 ± 0.3 yrs-old). RESULTS: We observed significant correlations for VO2peak during the 6-MWT as a function of WxD (R = 0.75, P < 0.0005), BM (R = 0.56, P < 0.0005), D (R = 0.43, P = 0.0004) and maximum HR (R = 0.37, P = 0.001). Distance correlated significantly with FAT (R = -0.43, P = 0.005), BMI (R = -0.36, P = 0.021) and age (R = -0.31, P < 0.045), whereas WxD correlated with BM (R = 0.86, P<0.005).The inclusion of WxD increased the R2 from 0.65 to 0.74 and decreased the estimative error while yielding the following equation (R = 0.86, standard error of the estimate (SEE) = 182.1 mL•min-1, P < 0.0005) to predict VO2peak: VO2peak = 962.2 + (0.037 x WxD) + (8.565 x maximum HR). A non-exercise model was obtained by univariate regressions but not multiple regressions. The FAT (R = 0.43, SEE = 702.2 m, P < 0.005) yielded the best model for predicting distance, i.e., distance = 702.2 - (3.067 x FAT). CONCLUSION: Our prediction model seems to accurately estimate VO2peak in healthy older men primarily when WxD is considered.

OBJETIVO: O teste de caminhada de seis minutos (TC6M) é uma estrategia simples e de baixo custo operacional que objetivamente mede a aptidão cardiorrespiratória de indivíduos com diferentes condições de saúde. Nosso objetivo foi desenvolver equações de predição da potência aeróbica em homens idosos saudáveis usando o TC6M. MÉTODOS: Foram medidos a composição corporal (massa corporal [MC], índice de massa corporal [BMI], porcentagem de gordura [%G]) e potência aeróbica de pico através de teste cardiopulmonar de exercício máximo (velocidade, frequência cardíaca [FC] e consumo de oxigênio [VO2] no limiar anaeróbico e no pico]) e através do TC6M (distancia [D], produto massa corporal x distância, FC e VO2de pico) em 76 idosos saudáveis com idade entre 65 e 80 anos (69.1 ± 0.3 anos). RESULTADOS: Foram observadas correlações significativas para VO2pico no TC6M em função do produto MCxD (R = 0,75, P < 0,0005), MC (R = 0,56, P < 0,0005), D (R = 0,43, P = 0,0004) e FC máxima (R = 0,37, P = 0,001). A correlacionou-se significativamente com %G (R = -0,43, P = 0,005), IMC (R = -0,36, P = 0,021) e idade (R = -0,31, P < 0,045), enquanto que a MCxD correlacionou-se com MC (R = 0,86, P < 0,005). A inclusão da MCxD aumentou o R 2 de 0,65 para 0,74 e diminuiu o erro padrão da estimativa (EPE) gerando a equação (R = 0,86, EPE = 182,1 mL·min-1, P < 0,0005) para a predição do VO2peak: VO2peak = 962,2 + (0,037 x MCxD) + (8,565 x FC máxima). Foi também gerado um modelo preditivo não dependente de exercício através de regressão univariada, mas não múltipla. A %G (R=0,43, EPE = 702,2 m, P < 0,005) gerou o melhor modelo para a predição da distancia, i.e., distancia = 702,2 - (3,067 x %G). CONCLUSÃO: Nossas modelos de predição parecem estimar precisamente o VO2pico de idosos saudáveis, especialmente quando a MCxD é considerada.

Predictors of muscle strength in older individuals / Preditores de força muscular em idosos

PURPOSE: To analyze possible relationships between load, body mass and lean body mass in an effort to provide norm-referenced standards for the one repetition maximum test and to predict whole body muscle strength (WBMS) in older individuals. METHODS: We measured body mass, lean body mass and the one repetition maximum (1RM) test in different exercises in 189 older men and women aged 61 to 82 years. Whole body muscle strength (WBMS) was calculated as the sum of loads of the different exercises. RESULTS: For women, the inclusion of body mass or lean body mass increased the R2 from 0.41 to 0.82, and yielded the following equation: WBMS = 75.788 + (2.288 × load in kg of latissimus pull down) + (0.799 × lean body mass in kg). For men, the inclusion of either body mass (WBMS = 290.33 - [3.140 × age in years] + [1.236 × body mass in kg] + [1.549 × load in kg of leg press]) or, in particular, lean body mass (WBMS = 343.25 - [3.298 × age in years] + [.415 × lean body mass in kg] + [1.737 × load in kg of leg press]) decreased the standard error of the estimate. CONCLUSION: Our data support the idea that load correlates with body mass and lean body mass and that the load used for a specific exercise is significantly associated with WBMS, thereby permitting the development of a predictive model of WBMS with increased accuracy.

OBJETIVO: Analisar as relações entre carga, massa corporal e massa magra na tentativa de fornecer normas padrão de referencia para o teste de uma repetição máxima e predizer a forca muscular corporal em idosos. MÉTODOS: A massa corporal, a massa magra e o teste de uma repetição máxima (1RM) foram medidos em 189 idosos com idade entre 61 e 82 anos. A forca muscular corporal (FMC) foi calculada como a somatória das cargas dos diferentes exercícios. RESULTADOS: Para mulheres, a inclusão da massa corporal ou da massa magra aumentou o R2 de 0.41 para 0.82, e resultou na equação: FMC = 75.788 + (2.288 × carga em kg para o puxador) + (0.799 × massa magra em kg). Para homens, a inclusão da massa corporal (FMC = 290.33 - [3.140 × idade em anos] + [1.236 × massa corporal em kg] + [1.549 × carga em kg para o leg press]) ou da massa magra (FMC = 343.25 - [3.298 × idade em anos] + [.415 × massa magra em kg] + [1.737 × carga em kg para o leg press]) diminuiu o erro padrão da estimativa. CONCLUSÃO: Nossos resultados suportam a ideia de que a carga correlaciona-se com a massa corporal e massa magra, e que a carga empregada em determinado exercício está significativamente associada com a forca muscular corporal. Portanto, isso permite o desenvolvimento de um modelo preditivo de forca muscular corporal com substancial acurácia.

Ultrastructural Morphology of Sperm from Human Globozoospermia.

Globozoospermia is a rare disorder characterized by the presence of sperm with round head, lacking acrosome. Coiling tail around the nucleus has been reported since early human studies, but no specific significance has conferred it. By contrast, studies on animal models suggest that coiling tail around the nucleus could represent a crucial step of defective spermatogenesis, resulting in round-headed sperm. No observations, so far, support the transfer of this hypothesis to human globozoospermia. The purpose of this work was to compare ultrastructural morphology of human and mouse model globozoospermic sperm. Sperm have been investigated by using scanning and transmission electron microscopy. The images that we obtained show significant similarities to those described in GOPC knockout mice, an animal model of globozoospermia. By using this model as reference, we were able to identify the probable steps of the tail coiling process in human globozoospermia. Although we have no evidence that there is the same pathophysiology in man and knocked-out mouse, the similarities between these ultrastructural observations in human and those in the experimental model are very suggestive. This is the first demonstration of the existence of relevant morphological homologies between the tail coiling in animal model and human globozoospermia.

The application of scanning near field optical imaging to the study of human sperm morphology.

BACKGROUND: The morphology of spermatozoa is a fundamental aspect to consider in fertilization, sperm pathology, assisted reproduction and contraception. Head, neck, midpiece, principal and terminal part of flagellum are the main sperm components to investigate for identifying morphological features and related anomalies. Recently, scanning near-field optical microscopy (SNOM), which belongs to the wide family of nanoscopic techniques, has opened up new routes for the investigation of biological systems. SNOM is the only technique able to provide simultaneously highly resolved topography and optical images with a resolution beyond the diffraction limit, typical of conventional optical microscopy. This offers the advantage to obtain complementary information about cell surface and cytoplasmatic structures. RESULTS: In this work human spermatozoa both healthy and with morphological anomalies are analyzed by SNOM, to demonstrate the potentiality of such approach in the visualization of sperm morphological details. The combination of SNOM topography with optical (reflection and transmission) images enables to examine typical topographic features of spermatozoa together with underlying cytoplasmic structures. Indeed the head shape and inner components as acrosome and nucleus, and the organization of mitochondria in the midpiece region are observed. Analogously for principal tract of the tail, the ridges and the columns are detected in the SNOM topography, while their internal arrangement can be observed in the corresponding SNOM optical transmission images, without requiring specific staining procedures or invasive protocols. CONCLUSIONS: Such findings demonstrate that SNOM represents a versatile and powerful tool to describe topographical and inner structural details of spermatozoa simultaneously. This analysis could be helpful for better characterizing several morphological anomalies, often related to sperm infertility, which cannot be examined by conventional techniques all together.

The effects of a session of resistance training on sleep patterns in the elderly.

The purpose of this study was to evaluate the influence of a session of resistance training on the sleep patterns of elderly people. Forty men aged 65-80 years who were sedentary and clinically healthy were divided into two groups: the control group (n = 18) and the resistance group (n = 22). Both groups underwent two polysomnography tests, one at baseline and another after either a resistance training session (the resistance group) or no physical exercise (the control group). The resistance training session was based on 60% of one repetition maximum (a test that assesses the maximum force). We observed that the frequency with which the control group awoke (arousal index) increased from 16.29 ± 6.06 events/h to 20.09 ± 6.9 events/h, and in the resistance group, it decreased from 22.27 ± 11 events/h to 20.41 ± 8.57 events/h (t = 2.10 and p = 0.04). For stage-1 sleep, there was an increase from 4.96% at baseline to 5.40% in the control group, and there was a decrease in the resistance group from 8.32 to 6.21% after the exercise session (t = 2.12 and p = 0.04). A session of resistance training at 60% of one repetition maximum was able to modify the sleep pattern in men aged 65-80 years, suggesting that physical exercise has a modest influence on sleep consolidation.

Exercise training improves sleep pattern and metabolic profile in elderly people in a time-dependent manner.

Aging and physical inactivity are two factors that favors the development of cardiovascular disease, metabolic syndrome, obesity, diabetes, and sleep dysfunction. In contrast, the adoption a habitual of moderate exercise may present a non-pharmacological treatment alternative for sleep and metabolic disorders. We aimed to assess the effects of moderate exercise training on sleep quality and on the metabolic profile of elderly people with a sedentary lifestyle. Fourteen male sedentary, healthy, elderly volunteers performed moderate training for 60 minutes/day, 3 days/week for 24 wk at a work rate equivalent to the ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2 °C, with an air humidity 60 ± 5%. Blood and polysomnographs analysis were collected 3 times: at baseline (1 week before training began), 3 and 6 months (after 3 and 6 months of training). Training promoted increasing aerobic capacity (relative VO2, time and velocity to VO2max; p < 0.05), and reduced serum NEFA, and insulin concentrations as well as improved HOMA index (p < 0.05), and increased adiponectin levels (p < 0.05), after 3 months of training when compared with baseline data. The sleep parameters, awake time and REM sleep latency were decreased after 6 months exercise training (p < 0.05) in relation baseline values. Our results demonstrate that the moderate exercise training protocol improves the sleep profile in older people, but the metabolism adaptation does not persist. Suggesting that this population requires training strategy modifications as to ensure consistent alterations regarding metabolism.

Gender differences in the sleep habits of 11-13 year olds / Diferenças nos hábitos de sono entre gêneros nos escolares de 11 a 13 anos de idade

OBJECTIVE: Sleep plays an important role in the physical and emotional development of adolescents. The aim of this study was to examine gender differences in sleep habits in a sample of 11-13 year olds. METHOD: The study was carried out in the city of Patos de Minas, Brazil. The study cohort was composed of 200 students (96 boys and 104 girls) attending (in the morning or in the afternoon) the 5th, 6th or 7th grades, with ages ranging from 11 to 13 years. A Sleep Questionnaire developed at the Federal University of São Paulo was used in order to evaluate student sleep habits and schedules, as well as the overall quality of sleep. RESULTS: For the period between Friday night and Sunday morning, girls displayed longer sleep duration than did boys. During the week, students attending only afternoon classes woke up later than did students attending only morning classes. In addition, morning-class students showed more adverse effects on sleep, including irregular sleep/wakefulness circadian rhythms, when compared with afternoon-class students. CONCLUSION: Sleep habits are affected by gender and school schedule.

OBJETIVO: O sono desempenha um papel fundamental no desenvolvimento físico e emocional de adolescentes. Este estudo teve o objetivo de analisar as diferenças entre gêneros nos hábitos de sono de escolares com idades entre 11 e 13. MÉTODO: Este estudo foi realizado na cidade de Patos de Minas-MG, Brasil. A amostra foi composta de 200 alunos (96 meninos e 104 meninas) matriculados da 5ª a 7ª séries (ambos os turnos, manhã e tarde) e com idade entre 11 e 13 anos. O Questionário de sono UNIFESP foi utilizado para avaliar a qualidade de sono, hábitos e horários de sono. RESULTADOS: As meninas demonstraram maior tempo de sono do que os meninos da sexta-feira à noite para o domingo de manhã. Os alunos que estudavam a tarde acordavam mais tarde que os alunos do turno matutino durante a semana; alunos do turno da manhã são mais afetados negativamente em relação ao sono e podem ter um ciclo vigília/sono irregular quando comparado com os alunos que estudam no turno da tarde. CONCLUSÃO: Meninos e meninas têm diferentes hábitos de sono, sendo influenciados pelo turno escolar.

Leukocytospermia and sperm preparation--a flow cytometric study.

BACKGROUND: Leukocytes represent the predominant source of reactive oxygen species both in seminal plasma and in sperm suspensions and have been demonstrated to negatively influence sperm function and fertilization rate in assisted reproduction procedures. Peroxidase test is the standard method recommended by WHO to detect semen leukocytes but it may be inaccurate. The aims of this study were (i) to compare the efficiency of swim-up and density-gradient centrifugation techniques in removing seminal leukocytes, (ii) to examine the effect of leukocytes on sperm preparation, and (iii) to compare flow cytometry and peroxidase test in determining leukocyte concentration in semen using a multiparameter flow cytometric method. METHODS: Semen samples from 126 male partners of couples undergoing infertility investigations were analyzed for leukocytospermia using standard optical microscopy and flow cytometry. Sixty-nine out of 126 samples were also processed using simultaneously the swim-up and density-gradient centrifugation techniques. A multiparameter flow cytometric analysis to assess simultaneously sperm concentration, sperm viability, sperm apoptosis, and leukocyte concentration was carried out on neat and prepared sperm. RESULTS: Both sperm preparation methods removed most seminal leukocytes. However, the concentration of leukocytes was significantly lower after swim-up compared to that after density-gradient centrifugation preparation. Leukocytes concentration, either initial or in prepared fractions, was not correlated with sperm parameters (optical microscopy and flow cytometry parameters) after semen processing. There was no correlation between leukocyte concentration in the ejaculate and sperm recovery rate, whereas a significant correlation was found between the concentration of the residual leukocytes in prepared fractions and viable sperm recovery rate. Although the overall concordance between the flow cytometry and the optical microscopy was satisfactory, the sensitivity of peroxidase test for the detection of leukocytospermia resulted low. CONCLUSION: Seminal leukocytes do not seem to influence sperm preparation results. However, for assisted conception, semen samples containing leukocytes should be processed using swim-up method. Although peroxidase-test is recommended by WHO as the standard method for determining semen leukocytes, it should not be used in clinical research study.

Gender differences in the sleep habits of 11-13 year olds.

OBJECTIVE: Sleep plays an important role in the physical and emotional development of adolescents. The aim of this study was to examine gender differences in sleep habits in a sample of 11-13 year olds. METHOD: The study was carried out in the city of Patos de Minas, Brazil. The study cohort was composed of 200 students (96 boys and 104 girls) attending (in the morning or in the afternoon) the 5th, 6th or 7th grades, with ages ranging from 11 to 13 years. A Sleep Questionnaire developed at the Federal University of São Paulo was used in order to evaluate student sleep habits and schedules, as well as the overall quality of sleep. RESULTS: For the period between Friday night and Sunday morning, girls displayed longer sleep duration than did boys. During the week, students attending only afternoon classes woke up later than did students attending only morning classes. In addition, morning-class students showed more adverse effects on sleep, including irregular sleep/wakefulness circadian rhythms, when compared with afternoon-class students. CONCLUSION: Sleep habits are affected by gender and school schedule.

Semen preparation methods and sperm apoptosis: swim-up versus gradient-density centrifugation technique.

OBJECTIVE: To compare the effects of density-gradient centrifugation and swim-up on sperm apoptosis by using a multiparameter flow cytometric method. DESIGN: Autocontrolled split-sample study. SETTING: Tertiary infertility center. PATIENT(S): Sixty-two male partners of couples undergoing infertility investigations. INTERVENTION(S): Each sample was analyzed both before and after semen preparation by optical microscopy and by flow cytometry. MAIN OUTCOME MEASURE(S): Percentage of viable, apoptotic, and necrotic sperm and recovery rate of total motile, progressive motile, and viable sperm before and after the two sperm preparation methods. RESULT(S): Compared with the original semen, the mean percentages of apoptotic and necrotic sperm were significantly lower after both sperm preparation methods. The mean percentage of viable sperm was significantly higher after swim-up compared with gradient centrifugation. The recovery rates of total motile, progressive motile, and viable sperm were significantly higher using gradient centrifugation compared with swim-up. The viable sperm percentage and the progressive sperm motility were significant predictors for negative difference between the two methods in terms of viable sperm percentage after preparation. CONCLUSION(S): Both sperm preparation methods allow obtaining a sperm population with a low percentage of apoptotic sperm. Therefore, the risk of using apoptotic sperm for clinical treatment seems to be rather low. The choice of method will depend on whether IVF/ICSI or intrauterine insemination is to be performed.

O exercício físico e os aspectos psicobiológicos / Physical exercise and the psychobiological aspects

O objetivo desta revisão é trazer parte dos estudos sobre um assunto pouco explorado: a relação entre o exercício físico e os aspectos psicobiológicos. A importância da compreensão desses aspectos e como eles afetam a qualidade de vida do ser humano é o que estimula as pesquisas sobre esse assunto. A literatura destaca que a prática regular de exercício físico traz resultados positivos não somente ao sono e aos seus possíveis distúrbios, mas também aos aspectos psicológicos e aos transtornos de humor, como a ansiedade e a depressão, e aos aspectos cognitivos, como a memória e a aprendizagem. Contudo, há indivíduos que se envolvem na prática de exercícios físicos com tal intensidade e/ou freqüência ou, ainda, fazem uso de drogas ilícitas que podem trazer prejuízos à saúde, como, por exemplo, o dependente de exercício físico e o usuário de esteróides anabolizantes. O exercício físico provoca alterações fisiológicas, bioquímicas e psicológicas, portanto, pode ser considerado uma intervenção não-medicamentosa para o tratamento de distúrbios relacionados aos aspectos psicobiológicos.

Análise de taxa metabólica basal e composição corporal de idosos do sexo masculino antes e seis meses após exercícios de resistência / Analysis of resting metabolic rate and body composition in elderly males before and after six months of endurance exercise

O objetivo deste trabalho foi o de comparar a taxa metabólica basal e a composição corporal antes e após um programa de exercício de resistência. Foram selecionados 46 voluntários do sexo masculino com idade entre 60 e 75 (66,97 ± 4,80 anos), que foram distribuídos aleatoriamente em dois grupos: 1) grupo controle, que foi orientado a não alterar seus hábitos rotineiros e não se engajar em nenhum programa de exercício físico; e 2) grupo experimental, que participou de um programa de exercícios em cicloergômetro três vezes por semana (60 minutos) em dias alternados por seis meses, com intensidade prescrita referente à freqüência cardíaca do limiar ventilatório 1 (LV-1). Os voluntários foram submetidos a avaliação da composição corporal (DEXA); calorimetria indireta, análise sanguínea e teste ergoespirométrico. Após o período de estudo, foram observados decréscimo significativo nos hormônios tireoidianos e mudanças no metabolismo basal em ambos os grupos, mas não foram constatadas alterações na composição corporal. No entanto, o grupo experimental apresentou aumento significativo no consumo de oxigênio pico e na carga de trabalho referente à intensidade do LV-1. Os dados sugerem que um programa de exercícios aeróbios na intensidade do LV-1 não é suficiente para provocar alterações favoráveis no metabolismo basal e composição corporal de idosos, embora promova benefícios cardiovasculares.

Evaluation of the antioxidant properties of propofol and its nitrosoderivative. comparison with homologue substituted phenols.

Propofol (2,6-diisopropylphenol), some substituted phenols (2,6-dimethylphenol and 2,6-ditertbutylphenol) and their 4-nitrosoderivatives have been compared for their scavenging ability towards 1,1-diphenyl-2-picrylhydrazyl and for their inhibitory action on lipid peroxidation. These products were also compared to the classical antioxidants butylated hydroxytoluene and butylated hydroxyanisole. When measuring the reactivity of the various phenolic derivatives with 1,1-diphenyl-2-picrylhydrazyl the following order of effectiveness was observed: butylated hydroxyanisole > propofol > 2,6-dimethylphenol > 2,6-di-tertbutylphenol > butylated hydroxytoluene. In cumene hydroperoxide-dependent microsomal lipid peroxidation, propofol acts as the most effective antioxidant, while butylated hydroxyanisole, 2,6-di-tertbutylphenol and butylated hydroxytoluene exhibit a rather similar effect, although lower than propofol. In the iron/ascorbate-dependent lipid peroxidation propofol, at concentrations higher than 10 microM, exhibits antioxidant properties comparable to those of butylated hydroxytoluene and butylated hydroxyanisole, 2,6-Dimethylphenol is scarcely effective in both lipoperoxidative systems. The antioxidant properties of the various molecules depend on their hydrophobic characteristics and on the steric and electronic effects of their substituents. However, the introduction of the nitroso group in the 4-position almost completely removes the antioxidant properties of the examined compounds. The nitrosation of the aromatic ring of antioxidant molecules and the consequent loss of antioxidant capacity can be considered a condition potentially occurring in vivo since nitric oxide and its derivatives are continuously formed in biological systems.

Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative.

1 Gold(I)-thiolate drugs are compounds that specifically interact with thiol and/or selenol groups and are essentially utilized in the treatment of rheumatoid arthritis. 2 Considering the importance of thiol groups in regulating mitochondrial membrane permeability, the effects of auranofin (S-triethylphosphinegold(I)-2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranoside), a second-generation gold drug, were studied on mitochondria isolated from rat liver. 3 Auranofin, at submicromolar concentrations, was able to induce the mitochondrial membrane permeability transition observed as swelling and loss of membrane potential. Both events are completely inhibited by cyclosporin A, the specific inhibitor of mitochondrial permeability transition. Calcium ions and energization by succinate are required for the occurrence of permeability transition. 4 By interacting with the active site selenol group, auranofin results as an extremely potent inhibitor of mitochondrial thioredoxin reductase, both isolated and in its mitochondrial environment. 5 It is concluded that auranofin, in the presence of calcium ions, is a highly efficient inducer of mitochondrial membrane permeability transition, potentially referable to its inhibition of mitochondrial thioredoxin reductase.