Impact of environmental mercury exposure on the blood cells oxidative status of fishermen living around Mundaú lagoon in Maceió - Alagoas (AL), Brazil.

Mercury in the aquatic environment can lead to exposure of the human population and is a known toxic metal due to its capacity for accumulation in organs. We aimed to evaluate the mercury level in the blood and urine of fishermen and correlate it with the level of oxidative stress in blood cells. We show in this case-control study that the fishermen of the exposed group (case) of Mundaú Lagoon (Maceió - Alagoas, Brazil) have higher concentrations of total mercury in the blood (0.73-48.38 µg L-1) and urine (0.430-10.2 µg L-1) than the total mercury concentrations in blood (0.29-17.30 µg L-1) and urine (0.210-2.65 µg L-1) of the control group. In the blood cells of fishermen, we observed that the lymphomononuclear cells produced high levels of reactive oxygen species (61.7%), and the erythrocytes presented increased lipid peroxidation (151%) and protein oxidation (41.0%) and a decrease in total thiol (36.5%), GSH and the REDOX state (16.5%). The activity of antioxidant system enzymes (SOD, GPx, and GST) was also reduced in the exposed group by 26.9%, 28.3%, and 19.0%, respectively. Furthermore, hemoglobin oxygen uptake was decreased in the exposed group (40.0%), and the membrane of cells presented increased osmotic fragility (154%) compared to those in the control group. These results suggest that mercury in the blood of fishermen can be responsible for causing impairments in the oxidative status of blood cells and is probably the cause of the reduction in oxygen uptake capacity and damage to the membranes of erythrocytes.

Neonatal treatment with fluoxetine improves mitochondrial respiration and reduces oxidative stress in liver of adult rats.

Recent studies have shown that exposure to fluoxetine treatment induces excessive production of ROS, and alters the antioxidant defense system in various tissues and cell types, mainly the liver. When fluoxetine is administered intraperitoneally, the drug rapidly reaches high concentrations in the liver, has potentially multiple toxic effects on energy metabolism in rat liver mitochondria. The aim of this study was to evaluate the effect of pharmacological treatment with fluoxetine during critical period for development on the mitochondrial bioenergetics and oxidative stress in liver of rat adult. To perform this study, the rat pups received Fx, or vehicle (Ct) from postnatal day 1 to postnatal day 21 (ie, during lactation period). We evaluated mitochondrial oxygen consumption, respiratory control ratio, ROS production, mitochondrial swelling by pore opening, oxidative stress biomarkers, and antioxidant defense in liver of rats at 60 days of age. Our studies have shown, that treatment with Fx during the lactation period resulted in reduced body mass gain, improvement of the mitochondrial respiratory capacity, induced higher mitochondrial resistance to calcium ion preventing the mitochondrial permeability transition pore opening, as well as decreased oxidative stress biomarkers, and increased the SH levels and enzymes antioxidant activities (SOD, CAT, GST) in liver of treated rats at 60 days of age. These findings suggest that pharmacological treatment with fluoxetine during critical period of development result in positive changes in liver of rats, as improvement of the mitochondrial bioenergetics and hepatic oxidative metabolism that persist in adulthood.

Oxidative injuries induced by maternal low-protein diet in female brainstem.

Many studies have shown that a maternal low-protein diet increases the susceptibility of offspring to cardiovascular disease in later-life. Moreover, a lower incidence of cardiovascular disease in females than in males is understood to be largely due to the protective effect of high levels of estrogens throughout a woman's reproductive life. However, to our knowledge, the role of estradiol in moderating the later-life susceptibility of offspring of nutrient-deprived mothers to cardiovascular disease is not fully understood. The present study is aimed at investigating whether oxidative stress in the brainstem caused by a maternal low-protein diet administered during a critical period of fetal/neonatal brain development (i.e during gestation and lactation) is affected by estradiol levels. Female Wistar rat offspring were divided into four groups according to their mothers' diets and to the serum estradiol levels of the offspring at the time of testing: (1) 22 days of age/control diet: (2) 22 days of age/low-protein diet; (3) 122 days of age/control diet: (4) 122 days of age/low-protein diet. Undernutrition in the context of low serum estradiol compared to undernutrition in a higher estradiol context resulted in increased levels of oxidative stress biomarkers and a reduction in enzymatic and non-enzymatic antioxidant defenses. Total global oxy-score showed oxidative damage in 22-day-old rats whose mothers had received a low-protein diet. In the 122-day-old group, we observed a decrease in oxidative stress biomarkers, increased enzymatic antioxidant activity, and a positive oxy-score when compared to control. We conclude from these results that following a protein deficiency in the maternal diet during early development of the offspring, estrogens present at high levels at reproductive age may confer resistance to the oxidative damage in the brainstem that is very apparent in pre-pubertal rats.

The Cratylia mollis seed lectin induces membrane permeability transition in isolated rat liver mitochondria and a cyclosporine a-insensitive permeability transition in Trypanosoma cruzi mitochondria.

Previous results provided evidence that Cratylia mollis seed lectin (Cramoll 1,4) promotes Trypanosoma cruzi epimastigotes death by necrosis via a mechanism involving plasma membrane permeabilization to Ca(2+) and mitochondrial dysfunction due to matrix Ca(2+) overload. In order to investigate the mechanism of Ca(2+) -induced mitochondrial impairment, experiments were performed analyzing the effects of this lectin on T. cruzi mitochondrial fraction and in isolated rat liver mitochondria (RLM), as a control. Confocal microscopy of T. cruzi whole cell revealed that Cramoll 1,4 binding to the plasma membrane glycoconjugates is followed by its internalization and binding to the mitochondrion. Electrical membrane potential (∆Ψm ) of T. cruzi mitochondrial fraction suspended in a reaction medium containing 10 µM Ca(2+) was significantly decreased by 50 µg/ml Cramoll 1,4 via a mechanism insensitive to cyclosporine A (CsA, membrane permeability transition (MPT) inhibitor), but sensitive to catalase or 125 mM glucose. In RLM suspended in a medium containing 10 µM Ca(2+) this lectin, at 50 µg/ml, induced increase in the rate of hydrogen peroxide release, mitochondrial swelling, and ∆Ψm disruption. All these mitochondrial alterations were sensitive to CsA, catalase, and EGTA. These results indicate that Cramoll 1, 4 leads to inner mitochondrial membrane permeabilization through Ca(2+) dependent mechanisms in both mitochondria. The sensitivity to CsA in RLM characterizes this lectin as a MPT inducer and the lack of CsA effect identifies a CsA-insensitive MPT in T. cruzi mitochondria.

Hepatoprotective effect of the aqueous extract of Simarouba amara Aublet (Simaroubaceae) stem bark against carbon tetrachloride (CCl4)-induced hepatic damage in rats.

Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle-corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver.

Moderate aerobic training counterbalances the deleterious effect of undernutrition on oxidative balance and mitochondrial markers.

The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Diet enriched in saturated fatty acids induces liver oxidative stress and elicits inflammatory pathways prior to metabolic disruption in perinatal protein undernutrition.

The impact of diets high in saturated fatty acids in individuals who have undergone maternal protein restriction is not clear. Here, we tested the hypothesis that a saturated fatty acid-enriched hyperlipidic diet (HL) affects liver expression of genes of the redox balance and inflammatory pathway in postweaning rat offspring subjected to maternal protein restriction. Pregnant Wistar rats received either a control (C; 19% protein) or low protein (LP; 8% protein) diet during gestation and lactation. At weaning, pups received either C or HL diets up to 90 days of life. The LP+HL group showed an upregulation of transcription of peroxisome proliferator-activated receptor γ (+48%) and peroxisome proliferator-activated receptor γ coactivator α (+96%) compared with the LP+C group (P < .05), respectively. Similarly, gene expression of the markers of inflammation, nuclear factor-kappa B1 (+194%) and tumor necrosis factor-α (+192%), was enhanced (P < .05). Although other antioxidant enzymes were not modified in gene expression, catalase (CAT) was 66% higher in LP+HL compared with LP+C. In contrast, CAT protein content in the liver was 50% lower in LP groups compared with C, and superoxide dismutase 2 (SOD2) was twice as high in LP groups compared with C. Postweaning HL after maternal protein restriction induces hepatic metabolic adaptation characterized by enhanced oxidative stress, unbalanced expression in the antioxidant enzymes SOD1, SOD2 and CAT, and activation of inflammatory pathways but does not impact circulating markers of lipid metabolism and liver function.

Seroprevalence of SARS-CoV-2 on health professionals via Bayesian estimation: a Brazilian case study before and after vaccines.

The increasing number of COVID-19 infections brought by the current pandemic has encouraged the scientific community to analyze the seroprevalence in populations to support health policies. In this context, accurate estimations of SARS-CoV-2 antibodies based on antibody tests metrics (e.g., specificity and sensitivity) and the study of population characteristics are essential. Here, we propose a Bayesian analysis using IgA and IgG antibody levels through multiple scenarios regarding data availability from different information sources to estimate the seroprevalence of health professionals in a Northeastern Brazilian city: no data available, data only related to the test performance, data from other regions. The study population comprises 432 subjects with more than 620 collections analyzed via IgA/IgG ELISA tests. We conducted the study in pre- and post-vaccination campaigns started in Brazil. We discuss the importance of aggregating available data from various sources to create informative prior knowledge. Considering prior information from the USA and Europe, the pre-vaccine seroprevalence means are 8.04% and 10.09% for IgG and 7.40% and 9.11% for IgA. For the post-vaccination campaign and considering local informative prior, the median is 84.83% for IgG, which confirms a sharp increase in the seroprevalence after vaccination. Additionally, stratification considering differences in sex, age (younger than 30 years, between 30 and 49 years, and older than 49 years), and presence of comorbidities are provided for all scenarios.

Mitochondria generated nitric oxide protects against permeability transition via formation of membrane protein S-nitrosothiols.

Mitochondria generated nitric oxide (NO) regulates several cell functions including energy metabolism, cell cycling, and cell death. Here we report that the NO synthase inhibitors (L-NAME, L-NNA and L-NMMA) administered either in vitro or in vivo induce Ca2+-dependent mitochondrial permeability transition (MPT) in rat liver mitochondria via a mechanism independent on changes in the energy state of the organelle. MPT was determined by the occurrence of cyclosporin A sensitive mitochondrial membrane potential disruption followed by mitochondrial swelling and Ca2+ release. In in vitro experiments, the effect of NOS inhibitors was dose-dependent (1 to 50 microM). In addition to cyclosporin A, L-NAME-induced MPT was sensitive to Mg2+ plus ATP, EGTA, and to a lower degree, to catalase and dithiothreitol. In contrast to L-NAME, its isomer D-NAME did not induce MPT. L-NAME-induced MPT was associated with a significant decrease in both the rate of NO generation and the content of mitochondrial S-nitrosothiol. Acute and chronic in vivo treatment with L-NAME also promoted MPT and decreased the content of mitochondrial S-nitrosothiol. SNAP (a NO donor) prevented L-NAME mediated MPT and reversed the decrease in the rate of NO generation and in the content of S-nitrosothiol. We propose that S-nitrosylation of critical membrane protein thiols by NO protects against MPT.

Goa1p of Candida albicans localizes to the mitochondria during stress and is required for mitochondrial function and virulence.

Using a Tn7 transposon library of Candida albicans, we have identified a mutant that exhibited sensitivity in drop plate assays to oxidants such as menadione and hydrogen peroxide. To verify the role of the mutated gene in stress adaptation, null mutants were constructed and phenotypically characterized. Because of its apparent functions in growth and oxidant adaptation, we have named the gene GOA1. Goa1p appears to be unique to the CTG subclade of the Saccharomycotina, including C. albicans. Mutants of C. albicans lacking goa1 (strain GOA31) were more sensitive to 6 mM H(2)O(2) and 0.125 mM menadione than the wild type (wt) or a gene-reconstituted (GOA32) strain. The sensitivity to oxidants correlated with reduced survival of the GOA31 mutant in human neutrophils and avirulence compared to control strains. Other phenotypes of GOA31 include reduced growth and filamentation in 10% serum, Spider, and SLAD agar media and an inability to form chlamydospores. Since Goa1p has an N-terminal mitochondrion localization site, we also show that green fluorescent protein-tagged Goa1p shows a mitochondrionlike distribution during oxidant or osmotic stress. Further, the inability of GOA31 to grow in medium containing lactate, ethanol, or glycerol as the sole carbon source indicates that the mitochondria are defective in the mutant. To determine how Goa1p contributes to mitochondrial function, we compared the wt, GOA32, and GOA31 strains for mitochondrial electrical membrane potential, respiration, and oxidative phosphorylation. We now show that GOA31, but not the wt or GOA32, had decreased respiration and mitochondrial membrane potential such that mutant cells are unable to drive oxidative phosphorylation. This is the first report in C. albicans of a respiratory defect caused by a loss of mitochondrial membrane potential.

Mitochondrial calcium overload triggers complement-dependent superoxide-mediated programmed cell death in Trypanosoma cruzi.

The epimastigote stage of Trypanosoma cruzi undergoes PCD (programmed cell death) when exposed to FHS (fresh human serum). Although it has been known for over 30 years that complement is responsible for FHS-induced death, the link between complement activation and triggering of PCD has not been established. We have previously shown that the mitochondrion participates in the orchestration of PCD in this model. Several changes in mitochondrial function were described, and in particular it was shown that mitochondrion-derived O(2)(*-) (superoxide radical) is necessary for PCD. In the present study, we establish mitochondrial Ca(2+) overload as the link between complement deposition and the observed changes in mitochondrial physiology and the triggering of PCD. We show that complement activation ends with the assembly of the MAC (membrane attack complex), which allows influx of Ca(2+) and release of respiratory substrates to the medium. Direct consequences of these events are accumulation of Ca(2+) in the mitochondrion and decrease in cell respiration. Mitochondrial Ca(2+) causes partial dissipation of the inner membrane potential and consequent mitochondrial uncoupling. Moreover, we provide evidence that mitochondrial Ca(2+) overload is responsible for the increased O(2)(*-) production, and that if cytosolic Ca(2+) rise is not accompanied by the accumulation of the cation in the mitochondrion and consequent production of O(2)(*-), epimastigotes die by necrosis instead of PCD. Thus our results suggest a model in which MAC assembly on the parasite surface allows Ca(2+) entry and its accumulation in the mitochondrion, leading to O(2)(*-) production, which in turn constitutes a PCD signal.

Saturated Fatty Acid-Enriched Diet-Impaired Mitochondrial Bioenergetics in Liver From Undernourished Rats During Critical Periods of Development.

The nutritional transition that the western population has undergone is increasingly associated with chronic metabolic diseases. In this work, we evaluated a diet rich in saturated fatty acids (hyperlipidic, HL) after weaning of the offspring rats submitted to maternal protein restriction on the hepatic mitochondrial bioenergetics. Wistar rats were mated and during gestation and lactation, mothers received control diets (NP, normal protein content 17%) or low protein (LP, 8% protein). After weaning, rats received either NL (normolipidic) or HL (+59% SFA) diets up to 90 days of life. It was verified that all respiratory states of hepatic mitochondria showed a reduction in the LP group submitted to the post-weaning HL diet. This group also presented greater mitochondrial swelling compared to controls, potentiated after Ca2+ addition and prevented in the presence of EGTA (calcium chelator) and cyclosporin A (mitochondrial permeability transition pore inhibitor). There was also an increase in liver protein oxidation and lipid peroxidation and reduction in catalase and glutathione peroxidase activities in the LP group fed HL diet after weaning. Our data suggest that adult rats subjected to maternal protein restriction were more susceptible to hepatic mitochondrial damage caused by a diet rich in saturated fatty acids post-weaning.

Maternal Protein Restriction in Two Successive Generations Impairs Mitochondrial Electron Coupling in the Progeny's Brainstem of Wistar Rats From Both Sexes.

Maternal protein deficiency during the critical development period of the progeny disturbs mitochondrial metabolism in the brainstem, which increases the risk of developing cardiovascular diseases in the first-generation (F1) offspring, but is unknown if this effect persists in the second-generation (F2) offspring. The study tested whether mitochondrial health and oxidative balance will be restored in F2 rats. Male and female rats were divided into six groups according to the diet fed to their mothers throughout gestation and lactation periods. These groups were: (1) normoprotein (NP) and (2) low-protein (LP) rats of the first filial generation (F1-NP and F1-LP, respectively) and (3) NP and (4) LP rats of the second filial generation (F2-NP and F2-LP, respectively). After weaning, all groups received commercial chow and a portion of each group was sacrificed on the 30th day of life for determination of mitochondrial and oxidative parameters. The remaining portion of the F1 group was mated at adulthood and fed an NP or LP diet during the periods of gestation and lactation, to produce progeny belonging to (5) F2R-NP and (6) F2R-LP group, respectively. Our results demonstrated that male F1-LP rats suffered mitochondrial impairment associated with an 89% higher production of reactive species (RS) and 137% higher oxidative stress biomarkers, but that the oxidative stress was blunted in female F1-LP animals despite the antioxidant impairment. In the second generation following F0 malnutrition, brainstem antioxidant defenses were restored in the F2-LP group of both sexes. However, F2R-LP offspring, exposed to LP in the diets of the two preceding generations displayed a RS overproduction with a concomitant decrease in mitochondrial bioenergetics. Our findings demonstrate that nutritional stress during the reproductive life of the mother can negatively affect mitochondrial metabolism and oxidative balance in the brainstem of F1 progeny, but that restoration of a normal diet during the reproductive life of those individuals leads toward a mitochondrial recovery in their own (F2) progeny. Otherwise, if protein deprivation is continued from the F0 generation and into the F1 generation, the F2 progeny will exhibit no recovery, but instead will remain vulnerable to further oxidative damage.

Twice-a-day training improves mitochondrial efficiency, but not mitochondrial biogenesis, compared with once-daily training.

Exercise training performed with lowered muscle glycogen stores can amplify adaptations related to oxidative metabolism, but it is not known if this is affected by the "train-low" strategy used (i.e., once-daily versus twice-a-day training). Fifteen healthy men performed 3 wk of an endurance exercise (100-min) followed by a high-intensity interval exercise 2 (twice-a-day group, n = 8) or 14 h (once-daily group, n = 7) later; therefore, the second training session always started with low muscle glycogen in both groups. Mitochondrial efficiency (state 4 respiration) was improved only for the twice-a-day group (group × training interaction, P < 0.05). However, muscle citrate synthase activity, mitochondria, and lipid area in intermyofibrillar and subsarcolemmal regions, and PGC1α, PPARα, and electron transport chain relative protein abundance were not altered with training in either group (P > 0.05). Markers of aerobic fitness (e.g., peak oxygen uptake) were increased, and plasma lactate, O2 cost, and rating of perceived exertion during a 100-min exercise task were reduced in both groups, although the reduction in rating of perceived exertion was larger in the twice-a-day group (group × time × training interaction, P < 0.05). These findings suggest similar training adaptations with both training low approaches; however, improvements in mitochondrial efficiency and perceived effort seem to be more pronounced with twice-a-day training.NEW & NOTEWORTHY We assessed, for the first time, the differences between two "train-low" strategies (once-daily and twice-a-day) in terms of training-induced molecular, functional, and morphological adaptations. We found that both strategies had similar molecular and morphological adaptations; however, only the twice-a-day strategy increased mitochondrial efficiency and had a superior reduction in the rating of perceived exertion during a constant-load exercise compared with once-daily training. Our findings provide novel insights into skeletal muscle adaptations using the "train-low" strategy.

Developmental Origins of Cardiometabolic Diseases: Role of the Maternal Diet.

Developmental origins of cardiometabolic diseases have been related to maternal nutritional conditions. In this context, the rising incidence of arterial hypertension, diabetes type II, and dyslipidemia has been attributed to genetic programming. Besides, environmental conditions during perinatal development such as maternal undernutrition or overnutrition can program changes in the integration among physiological systems leading to cardiometabolic diseases. This phenomenon can be understood in the context of the phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental input without genetic change, following a novel, or unusual input during development. Experimental studies indicate that fetal exposure to an adverse maternal environment may alter the morphology and physiology that contribute to the development of cardiometabolic diseases. It has been shown that both maternal protein restriction and overnutrition alter the central and peripheral control of arterial pressure and metabolism. This review will address the new concepts on the maternal diet induced-cardiometabolic diseases that include the potential role of the perinatal malnutrition.

The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress.

Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at -80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood.

Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam.

Syphilis, leprosy, and human immunodeficiency virus coinfection: a challenging diagnosis.

The association between syphilis, leprosy, and human immunodeficiency virus (HIV) is not well documented, and the emergence of isolated cases raises the interest and indicates that this triple coinfection can occur. We report the case of a 42-year-old man from Rio de Janeiro, Brazil, who presented with erythematous papules on the trunk, back, and upper and lower extremities; an erythematous plaque on the upper abdomen; and an erythematous violaceous plaque on the right thigh with altered sensitivity. Laboratory investigation showed a reagent VDRL test (1:512) and positive test results for Treponema pallidum hemagglutination. Treatment with benzathine penicillin (2,400,000 U intramuscularly) was started (2 doses 1 week apart). On follow-up 40 days later, the lesions showed partial improvement with persistence of the plaques on the right thigh and upper abdomen as well as a new similar plaque on the back. Further laboratory examinations showed negative bacilloscopy, positive HIV test, and histologic findings consistent with tuberculoid leprosy. The patient was started on multidrug therapy for paucibacillary leprosy with clinical improvement; the patient also was monitored by the HIV/AIDS department. We emphasize the importance of clinical suspicion for a coinfection case despite the polymorphism of these diseases as well as the precise interpretation of laboratory and histopathology examinations to correctly manage atypical cases.

Moderate physical training counterbalances harmful effects of low-protein diet on heart: metabolic, oxidative and morphological parameters

Aims: Maternal low-protein diet induces several impairments on cardiac system. Conversely, moderate exercise has been widely recommended to health improvement due to its effects on heart function. Thus, we investigated whether the moderate physical training is capable to offset the lasting injuries of a maternal protein restriction on the hearts of male adult rats. Methods: Pregnant rats were divided into two groups: Control (C=17% casein) and undernutrition (U=8% casein). Offspring from the undernutrition group, at 60 days of life, were subdivided into undernutrition (U) and undernutrition+exercise (UT) groups. Treadmill exercise was performed: (8 weeks, 5 days/week, 60 min/day at 70% of VO2máx). 48 hours after last exercise session, tissues were collected for morphological and biochemical analysis. Results Despite the deleterious effect induced by low-protein diet, physical training was able to restore morphological parameters to similar levels to the control group. Additionally, oxidative stress index was also improved in UT group, due to the increase in antioxidant enzymatic defense. In metabolic enzymes, maternal low-protein diet induced a change in metabolism, and moderate physical training improved oxidative metabolism. Conclusion: We demonstrated that moderate physical training can offset the cardiac metabolism in adult rats that were exposed to a maternal low-protein diet.(AU)