O26 Polysaccharides as Key Players in Enteropathogenic E. coli Immune Evasion and Vaccine Development.

Enteropathogenic Escherichia coli (EPEC) produce a capsule of polysaccharides identical to those composing the O-antigen polysaccharide of its LPS (lipopolysaccharide) molecules. In light of this, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC compared to non-capsulated enterohemorrhagic Escherichia coli (EHEC) was investigated. Our findings reveal that there was no significant difference between the levels in EPEC and EHEC of rhamnose (2.8:2.5), a molecule considered to be a PAMP (Pathogen Associated Molecular Patterns). However, the levels of glucose (10:1.69), heptose (3.6:0.89) and N-acetylglucosamine (4.5:2.10), were significantly higher in EPEC than EHEC, respectively. It was also observed that the presence of a capsule in EPEC inhibited the deposition of C3b on the bacterial surface and protected the pathogen against lysis by the complement system. In addition, the presence of a capsule also protected EPEC against phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies, and additionally, these antibodies were able to inhibit O26 EPEC adhesion to human epithelial cells. Finally, the results indicate that O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the development of a vaccine against capsulated O26 E. coli.

Detailed Characterization of Brain Dysfunction in a Long-Term Rodent Model of Critical Illness.

Critical illness encompasses a wide spectrum of life-threatening clinical conditions requiring intensive care. Our objective was to evaluate cognitive, inflammatory and cellular metabolism alterations in the central nervous system in an animal model of critical illness induced by zymosan. For this Wistar rats that were divided into Sham and zymosan. Zymozan was administered once intraperitoneally (30 g/100 g body weight) diluted in mineral oil. The animals were submitted to behavioral tests of octagonal maze, inhibitory avoidance and elevated plus maze. Brain structures (cortex, prefrontal and hippocampus) were removed at 24 h, 4, 7 and 15 days after zymosan administration for analysis of cytokine levels (TNF-α, IL-1b, IL-6 and IL-10), oxidative damage and oxygen consumption. Zymosan-treated animals presented mild cognitive impairment both in aversive (inhibitory avoidance) and non-aversive (octagonal maze) tasks by day 15. However, they did not show increase in anxiety (elevated-plus maze). The first neurochemical alteration found was an increase in brain pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) at day 4th in the hippocampus. In cortex, a late (7 and 15 days) increase in TNF-α was also noted, while the anti-inflammatory cytokine IL-10 decrease from 4 to 15 days. Oxygen consumption was decreased in the hippocampus and pre-frontal, but not cortex, only at 7 days. Additionally, it was observed a late (15 days) increase in oxidative damage parameters. This characterization of brain dysfunction in rodent model of critical illness reproduces some of the alterations reported in humans such neuropsychiatric disorders, especially depression, memory loss and cognitive changes and can add to the nowadays used models.

Interactions of temperature and dietary composition on juvenile European lobster (Homarus gammarus, L.) energy metabolism and performance.

Optimal rearing temperatures for European lobster Homarus gammarus in aquaculture differ from those prevalent in their aquatic ecosystems and acclimating juveniles to the prevailing temperatures before release may aid in the success of re-stocking programs. As the dietary nutritional composition is important for optimal performance of H. gammarus, in this study we aimed to investigate whether juvenile growth and energy metabolism responses to temperature variation could be modulated by the diet. Prior to the trial start, the juveniles were divided into two groups. One was maintained at 19 °C and the other gradually adapted to 13 °C. From this point and for a 24-day period, juveniles (~ 100 mg) within each temperature group were assigned one of two experimental diets: a carbohydrate-rich (HC) or a protein-rich (HP) extruded feed. Antarctic krill (AK) was used as a control diet within each temperature group. Feed intake, growth, glycogen, glucose, lactate, and protein concentrations of H. gammarus in each group were evaluated. Regardless the dietary treatment, feed intake, cephalothorax protein and glucose, and abdominal glycogen and glucose levels decreased at colder temperature. The effect of lower temperature on growth (SGR and moulting rate declines) and energy metabolism (reduction on cephalothorax glycogen and protein) was more severe in HC-fed lobsters. Results showed that the impact of lower temperature on juvenile H. gammarus can be modulated by diet highlighting the importance of designing optimized diets not only for growth and feed efficiency but also for resilience to environmental variation.

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases.

Stem cell therapy is a promising alternative approach to heart diseases. The most prevalent source of multipotent stem cells, usually called somatic or adult stem cells (mesenchymal stromal/stem cells, MSCs) used in clinical trials is bone marrow (BM-MSCs), adipose tissue (AT-MSCs), umbilical cord (UC-MSCs) and placenta. Therapeutic use of MSCs in cardiovascular diseases is based on the benefits in reducing cardiac fibrosis and inflammation that compose the cardiac remodeling responsible for the maintenance of normal function, something which may end up causing progressive and irreversible dysfunction. Many factors lead to cardiac fibrosis and failure, and an effective therapy is lacking to reverse or attenuate this condition. Different approaches have been shown to be promising in surpassing the poor survival of transplanted cells in cardiac tissue to provide cardioprotection and prevent cardiac remodeling. This review includes the description of pre-clinical and clinical investigation of the therapeutic potential of MSCs in improving ventricular dysfunction consequent to diverse cardiac diseases.

Lipid profile and fatty acid composition of marine fish species from Northeast coast of Brazil.

Total lipid content, fatty acid composition and nutritional profile of lipid fraction of fourteen fish species from the Brazilian Northeastern coast were evaluated. Lipid content was determined by Bligh and Dyer methodology, whereas the fatty acid composition was determined by gas chromatography with flame ionization detector. The indices of atherogenicity, thrombogenicity and hypocholesterolemic/hypercholesterolemic ratio were used to evaluate the nutritional quality of lipid fraction. The total lipid content ranged from 0.25 to 3.09%, with higher values in L. synagris. A significant difference (p < 0.05) were noted in fatty acids composition between the fourteen fish species. PUFA were the major fatty acids in twelve of fourteen species and C. leiarchus showed the highest content. The n-3 content ranged from 69.83 to 270.62 mg g-1 of total lipids, being EPA and DHA the major fatty acids in most of the species studied. The species L. synagris, M. bonaci and S. brasiliensis exceeded the WHO daily intake recommendation of 250 mg per day from those fatty acids. The quality indexes of the lipid fraction as well as the n-6/n-3 and PUFA/SFA ratios indicated that all fish species can be healthy nutritional options, and can bring many benefits to human health. The principal component analysis resulted in a two-principal-component model that described 79.78% of data variance. Also, it highlighted that despite the differences between the breeding strategies of fish families, the species could be grouped according to their similarity in fatty acids composition.

Ammonia exposition during gestation induces neonatal oxidative damage in the brain and long-term cognitive alteration in rats.

Ammonia is involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy. Few is known about the effects of gestational exposition to ammonia in the developing brain, and the possible long-term consequences of such exposure. We aimed to evaluate the effects of ammonia exposure during the gestation and the possible long-term cognitive alterations on pups. Eight female rats were divided into two groups: (1) control (saline solution); (2) ammonia (ammonium acetate, 2,5mmol/Kg). Each rat received a single subcutaneous injection during all gestational period. The brains from 1-day-old rats were obtained to the determination of thiobarbituric acid reactive species (TBARS), protein carbonyl and nitrite/nitrate levels. Some animals were followed 30 days after delivery and were subjected to the step-down inhibitory avoidance task. It was observed a significant increase in protein carbonyl, but not TBARS or nitrite/nitrate levels, in pups exposed to ammonia. Rats exposed to ammonia presented long-term cognitive impairment. Gestational exposition to ammonia induces protein oxidative damage in the neonatal rat brain, and long-term cognitive impairment.

Suppressors of superoxide production from mitochondrial complex III.

Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput screening, we identified compounds that selectively eliminate superoxide production by complex III without altering oxidative phosphorylation; they modulate retrograde signaling including cellular responses to hypoxic and oxidative stress.

Organizational barriers to the availability and insertion of intrauterine devices in Primary Health Care Services. / Barreiras organizacionais para disponibilização e inserção do dispositivo intrauterino nos serviços de atenção básica à saúde.

OBJECTIVE: To identify organizational barriers to IUD availability in Primary Health Care services from the perspective of women's health coordinators. METHOD: This is a quantitative study carried out with women's health officials from the municipalities of the southern macro region of Minas Gerais, Brazil, with an on-line completion of a structured instrument and a descriptive data analysis. RESULTS: 79 technicians participated in the study. Among the municipalities, 15.2% do not provide IUDs and 8.3% do not refer women to other services, 53.7% do not provide IUDs at basic health units. Among those who provide the IUD, 68.7% do not have a specific protocol and 10.5% do not adopt pregnancy as a condition that makes it impossible to insert the IUD, and 80.6% adopt unnecessary conditions, such as vaginal infection. As a criterion for IUD access, 86.5% referred to a medical prescription, 71.6% required exams, 44.6% were over 18 years of age and 24.4% participation in groups, none based on scientific evidence. Only the doctor inserted the IUD. CONCLUSION: Problems in the access to the IUD were identified due to organizational barriers to its availability and insertion, such as the lack of availability of the method or the excess of unnecessary criteria to make it available.

Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise.

The sites and rates of mitochondrial production of superoxide and H2O2 in vivo are not yet defined. At least 10 different mitochondrial sites can generate these species. Each site has a different maximum capacity (e.g. the outer quinol site in complex III (site IIIQo) has a very high capacity in rat skeletal muscle mitochondria, whereas the flavin site in complex I (site IF) has a very low capacity). The maximum capacities can greatly exceed the actual rates observed in the absence of electron transport chain inhibitors, so maximum capacities are a poor guide to actual rates. Here, we use new approaches to measure the rates at which different mitochondrial sites produce superoxide/H2O2 using isolated muscle mitochondria incubated in media mimicking the cytoplasmic substrate and effector mix of skeletal muscle during rest and exercise. We find that four or five sites dominate during rest in this ex vivo system. Remarkably, the quinol site in complex I (site IQ) and the flavin site in complex II (site IIF) each account for about a quarter of the total measured rate of H2O2 production. Site IF, site IIIQo, and perhaps site EF in the ß-oxidation pathway account for most of the remainder. Under conditions mimicking mild and intense aerobic exercise, total production is much less, and the low capacity site IF dominates. These results give novel insights into which mitochondrial sites may produce superoxide/H2O2 in vivo.

The contributions of respiration and glycolysis to extracellular acid production.

BACKGROUND: The rate at which cells acidify the extracellular medium is frequently used to report glycolytic rate, with the implicit assumption that conversion of uncharged glucose or glycogen to lactate(-)+H(+) is the only significant source of acidification. However, another potential source of extracellular protons is the production of CO2 during substrate oxidation: CO2 is hydrated to H2CO3, which then dissociates to HCO3(-)+H(+). METHODS: O2 consumption and pH were monitored in a popular platform for measuring extracellular acidification (the Seahorse XF Analyzer). RESULTS: We found that CO2 produced during respiration caused almost stoichiometric release of H(+) into the medium. With C2C12 myoblasts given glucose, respiration-derived CO2 contributed 34% of the total extracellular acidification. When glucose was omitted or replaced by palmitate or pyruvate, this value was 67-100%. Analysis of primary cells, cancer cell lines, stem cell lines, and isolated synaptosomes revealed contributions of CO2-produced acidification that were usually substantial, ranging from 3% to 100% of the total acidification rate. CONCLUSION: Measurement of glycolytic rate using extracellular acidification requires differentiation between respiratory and glycolytic acid production. GENERAL SIGNIFICANCE: The data presented here demonstrate the importance of this correction when extracellular acidification is used for quantitative measurement of glycolytic flux to lactate. We describe a simple way to correct the measured extracellular acidification rate for respiratory acid production, using simultaneous measurement of oxygen consumption rate. SUMMARY STATEMENT: Extracellular acidification is often assumed to result solely from glycolytic lactate production, but respiratory CO2 also contributes. We demonstrate that extracellular acidification by myoblasts given glucose is 66% glycolytic and 34% respiratory and describe a method to differentiate these sources.

The 2-oxoacid dehydrogenase complexes in mitochondria can produce superoxide/hydrogen peroxide at much higher rates than complex I.

Several flavin-dependent enzymes of the mitochondrial matrix utilize NAD(+) or NADH at about the same operating redox potential as the NADH/NAD(+) pool and comprise the NADH/NAD(+) isopotential enzyme group. Complex I (specifically the flavin, site IF) is often regarded as the major source of matrix superoxide/H2O2 production at this redox potential. However, the 2-oxoglutarate dehydrogenase (OGDH), branched-chain 2-oxoacid dehydrogenase (BCKDH), and pyruvate dehydrogenase (PDH) complexes are also capable of considerable superoxide/H2O2 production. To differentiate the superoxide/H2O2-producing capacities of these different mitochondrial sites in situ, we compared the observed rates of H2O2 production over a range of different NAD(P)H reduction levels in isolated skeletal muscle mitochondria under conditions that favored superoxide/H2O2 production from complex I, the OGDH complex, the BCKDH complex, or the PDH complex. The rates from all four complexes increased at higher NAD(P)H/NAD(P)(+) ratios, although the 2-oxoacid dehydrogenase complexes produced superoxide/H2O2 at high rates only when oxidizing their specific 2-oxoacid substrates and not in the reverse reaction from NADH. At optimal conditions for each system, superoxide/H2O2 was produced by the OGDH complex at about twice the rate from the PDH complex, four times the rate from the BCKDH complex, and eight times the rate from site IF of complex I. Depending on the substrates present, the dominant sites of superoxide/H2O2 production at the level of NADH may be the OGDH and PDH complexes, but these activities may often be misattributed to complex I.

Effects of primaquine and chloroquine on oxidative stress parameters in rats.

Primaquine and chloroquine are used for the treatment of malaria; evidence from the literature suggests that these drugs may induce oxidative stress. In this study we investigated the effects of primaquine and chloroquine on oxidative damage and DNA damage in brain, liver and kidney of rats after 7, 14 and 21 days of administration. Our results demonstrated that primaquine causes DNA damage in brain after 7, 14 and 21 days, and in liver after 7 and 14 days. Moreover, primaquine increases TBARS levels in the kidney and protein carbonyls in the brain after 14 days, and decreases protein carbonyls in the liver after 7 days. Whereas chloroquine causes DNA damage in the kidney after 7 and 14 days, and in the liver after 14 and 21 days, increases TBARS levels in the kidney after 7 days, and decreases TBARS levels in the brain after 21 days. Moreover, decreases protein carbonyls in the liver after 7 and 14 days, and in the brain after 7 and 21 days. However, chloroquine treatment for 14 days increases protein carbonyls in the brain and kidney. In conclusion, these results showed that prolonged treatment with antimalarial may adversely affect the DNA.

Silencing of maternal heme-binding protein causes embryonic mitochondrial dysfunction and impairs embryogenesis in the blood sucking insect Rhodnius prolixus.

The heme molecule is the prosthetic group of many hemeproteins involved in essential physiological processes, such as electron transfer, transport of gases, signal transduction, and gene expression modulation. However, heme is a pro-oxidant molecule capable of propagating reactions leading to the generation of reactive oxygen species. The blood-feeding insect Rhodnius prolixus releases enormous amounts of heme during host blood digestion in the midgut lumen when it is exposed to a physiological oxidative challenge. Additionally, this organism produces a hemolymphatic heme-binding protein (RHBP) that transports heme to pericardial cells for detoxification and to growing oocytes for yolk granules and as a source of heme for embryo development. Here, we show that silencing of RHBP expression in female fat bodies reduced total RHBP circulating in the hemolymph, promoting oxidative damage to hemolymphatic proteins. Moreover, RHBP knockdown did not cause reduction in oviposition but led to the production of heme-depleted eggs (white eggs). A lack of RHBP did not alter oocyte fecundation. However, produced white eggs were nonviable. Embryo development cellularization and vitellin yolk protein degradation, processes that normally occur in early stages of embryogenesis, were compromised in white eggs. Total cytochrome c content, cytochrome c oxidase activity, citrate synthase activity, and oxygen consumption, parameters that indicate mitochondrial function, were significantly reduced in white eggs compared with normal dark red eggs. Our results showed that reduction of heme transport from females to growing oocytes by RHBP leads to embryonic mitochondrial dysfunction and impaired embryogenesis.

Integrin participates in the effect of thyroxine on plasma membrane in immature rat testis.

BACKGROUND: The secretory activity of Sertoli cells (SC) is dependent on ion channel functions and protein synthesis and is critical to ongoing spermatogenesis. The aim of this study was to investigate the mechanism of action associated with a non-metabolizable amino acid [14C]-MeAIB (alpha-(methyl-amino)isobutyric acid) accumulation stimulated by T4 and the role of the integrin receptor in this event, and also to clarify whether the T4 effect on MeAIB accumulation and on Ca2+ influx culminates in cell secretion. METHODS: We have studied the rapid and plasma membrane initiated effects of T4 by using 45Ca2+ uptake and [45C]-MeAIB accumulation assays, respectively. Thymidine incorporation into DNA was used to monitor nuclear activity and quinacrine to analyze the secretory activity on SC. RESULTS: The stimulation of MeAIB accumulation byT4 appears to be mediated by the integrin receptor in the plasma membrane since tetrac and RGD peptide were able to nullify the effect of this hormone. In addition, T4 increases extracellular Ca2+ uptake and Ca2+ from intracellular stocks to enhance nuclear activity, but this genomic action seems not to influence SC secretion mediated by T4. Also, the cytoskeleton and CIC-3 chloride channel contribute to the membrane-associated responses of SC. CONCLUSIONS: T4 integrin receptor activation ultimately determines the plasma membrane responses on amino acid transport in SC, but it is not involved in calcium influx, cell secretion or the nuclear effect of the hormone. GENERAL SIGNIFICANCE: The integrin receptor activation by T4 may take a role in plasma membrane processes involved in the male reproductive system.

Factors associated with the length of breastfeeding during the COVID-19 pandemic: a survival study.

OBJECTIVE: To investigate the repercussions of COVID-19 on the length of breastfeeding and analyze the associated factors in Belo Horizonte, Minas Gerais, Brazil. METHOD: This is an epidemiological, prospective cohort study. Data were collected from medical records and through telephone interviews. Women who weaned were estimated using Kaplan-Meier survival analysis. The log-rank test was used to verify differences between groups, analyzing weaning time, according to sociodemographic and clinical characteristics. The values of hazard ratio and 95% confidence intervals were estimated using Cox regression analysis. RESULTS: A total of 1,729 women participated in the study. During the COVID-19 pandemic, brown women and women undergoing cesarean section were more likely to stop breastfeeding. CONCLUSION: The birth route and mothers' ethnic characteristics were associated with early weaning during the COVID-19 pandemic. Such findings are important to guide the assistance of the multidisciplinary team, especially nursing, during the post-pandemic period and in future epidemiological scenarios.

Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity.

The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.

Gastrointestinal Helminths in Wild Felids in the Cerrado and Pantanal: Zoonotic Bioindicators in Important Brazilian Biomes.

Environmental changes in the Brazilian Pantanal and Cerrado facilitate the spread of parasitic diseases in wildlife, with significant implications for public health owing to their zoonotic potential. This study aimed to examine the occurrence and diversity of gastrointestinal parasites in wild felids within these regions to assess their ecological and health impacts. We collected and analyzed helminth-positive samples from 27 wild felids using specific taxonomic keys. Diverse parasitic taxa were detected, including zoonotic helminths, such as Ancylostoma braziliense, Ancylostoma caninum, Ancylostoma pluridentatum, Toxocara cati, Toxocara canis, Dipylidium caninum, Taenia spp., Echinococcus spp., and Spirometra spp. Other nematodes, such as Physaloptera praeputialis and Physaloptera anomala, were identified, along with acanthocephalans from the genus Oncicola and a trematode, Neodiplostomum spp. (potentially the first record of this parasite in wild felids in the Americas). Human encroachment into natural habitats has profound effects on wild populations, influencing parasitic infection rates and patterns. This study underscores the importance of continuous monitoring and research on parasitic infections as a means of safeguarding both wildlife and human populations and highlights the role of wild felids as bioindicators of environmental health.

1α,25-dihydroxyvitamin D(3) mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats.

The involvement of calcium-mediated signaling pathways in the mechanism of action of 1α,25-dihydroxyvitamin D(3) (1,25D) is currently demonstrated. In this study we found that 1,25D induces nongenomic effects mediated by membrane vitamin D receptor (VDRm) by modulating intermediate filament (IF) phosphorylation and calcium uptake through L-type voltage-dependent calcium channels (L-VDCC) in cerebral cortex of 10 day-old rats. Results showed that the mechanism of action of 1,25D involves intra- and extracellular calcium levels, as well as the modulation of chloride and potassium channels. The effects of L-VDCCs on membrane voltage occur over a broad potential range and could involve depolarizing or hyperpolarizing coupling modes, supporting a cross-talk among Ca(2+) uptake and potassium and chloride channels. Also, the Na(+)/K(+)-ATPase inactivation by ouabain mimicked the 1,25D action on (45)Ca(2+) uptake. The Na(+)/K(+)-ATPase inhibition observed herein might lead to intracellular Na(+) accumulation with subsequent L-VDCC opening and consequently increased (45)Ca(2+) (calcium, isotope of mass 45) uptake. Moreover, the 1,25D effect is dependent on the activation of the following protein kinases: cAMP-dependent protein kinase (PKA), Ca(2+)/calmodulin-dependent protein kinase (PKCaMII), phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase p38 (p38(MAPK)). The modulation of calcium entry into neural cells by the 1,25D we are highlighting, might take a role in the regulation of a plethora of intracellular processes. Considering that vitamin D deficiency can lead to brain illness, 1,25D may be a possible candidate to be used, at least as an adjuvant, in the pharmacological therapy of neuropathological conditions.

Blood meal-derived heme decreases ROS levels in the midgut of Aedes aegypti and allows proliferation of intestinal microbiota.

The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS) generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF) mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox) reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.

Effect of acute administration of L-tyrosine on oxidative stress parameters in brain of young rats.

Tyrosinemia type II, also known as Richner-Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of L-tyrosine. Our results demonstrated that the acute administration of L-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of L-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II.