Nephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic ...compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidative stress and nitric oxide production. Also, there were increases of the mRNA levels for proinflammatory cytokines (tumor necrosis factor alpha TNF-α, interleukin-1β IL-1β, IL-2, and gamma interferon IFN-γ). Histopathological findings of tubular degeneration and inflammatory cell infiltration reinforced GM-induced nephrotoxicity. All these alterations were attenuated by previous oral treatment with GF. Animals from the GM+GF groups showed amelioration in renal function parameters and reduced lipid peroxidation and nitrosative stress, in addition to an increment in the levels of glutathione (GSH) and superoxide dismutase (SOD) activity. Gingerols also promoted significant reductions in mRNA transcription for TNF-α, IL-2, and IFN-γ. These effects were dose dependent. These results demonstrate that GF promotes a nephroprotective effect on GM-mediated nephropathy by oxidative stress, inflammatory processes, and renal dysfunction.
is a class III zoonotic bacterial pathogen able to survive and replicate inside host cells, including macrophages. Here we report a multidimensional transposon sequencing analysis to identify genes ...essential for
growth in rich medium and replication in RAW 264.7 macrophages. The construction of a dense transposon mutant library and mapping of 929,769 unique mini-Tn
insertion sites in the genome allowed identification of 491 essential coding sequences and essential segments in the
genome. Chromosome II carries a lower proportion (5%) of essential genes than chromosome I (19%), supporting the hypothesis of a recent acquisition of a megaplasmid as the origin of chromosome II. Temporally resolved transposon sequencing analysis as a function of macrophage infection stages identified 79 genes with a specific attenuation phenotype in macrophages, at either 2, 5, or 24 h postinfection, and 86 genes for which the attenuated mutant phenotype correlated with a growth defect on plates. We identified 48 genes required for intracellular growth, including the
operon, encoding the type IV secretion system, which supports the validity of the screen. The remaining genes encode amino acid and pyrimidine biosynthesis, electron transfer systems, transcriptional regulators, and transporters. In particular, we report the need of an intact pyrimidine nucleotide biosynthesis pathway in order for
to proliferate inside RAW 264.7 macrophages.
Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas ...to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with l-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under l-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.
Some patients with Parkinson's disease are offered treatment through surgery, which consists of delivering electrical current to regions deep within the brain. This study shows that stimulation of an area located on the brain surface, known as the secondary motor cortex, can also reverse movement disorders in mice. Authors have used a brain stimulation technique called optogenetics, which allowed targeting a specific type of surface neuron that communicates with the deep part of the brain involved in movement control. The study also shows that a combination of this stimulation with drug treatment might be useful to treat memory impairment, a kind of cognitive problem in Parkinson's disease.
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•Deep tillage in shallow and dense soils increases water infiltration and conductivity.•Soil conservation management reduces the main driver of surface crusting in Inceptisols.•Soil ...mixing equipment used in coffee furrowing increases soil air and water availability; and•Brachiaria-grass intercropped with coffee improved infiltration and soil hydraulic conductivity.
Soil management operations change soil porosity, affecting water infiltration, redistribution, storage, availability, and uptake by plants. Assessing how soil management may affect pore size distribution and hydraulic conductivity is thus highly relevant for rainfed agriculture coping with water shortage. The aim of this study was to assess the effectiveness of tillage treatments, designed to deepen coffee plants root system, on improving structure and physical-hydric attributes of an Inceptisol with a shallow solum. The study was conducted in an experimental area in the municipality of Nazareno, Minas Gerais State, Brazil. Soil samples were collected 18 months after coffee plantation, at different depths (0, 0.25, 0.35, 0.45, 0.55, 0.66, and 0.75 m) and they were used to determine pore-size distribution, saturated and unsaturated hydraulic conductivity. Samples were also collected in surface crusts or in the 0−0.005 m soil layer for detailed grain size analysis. Field water infiltration was measured at different water tensions. Coffee seedlings were planted in rows furrowed to depths depending on tillage treatment: 0.4 m depth, made by a furrow ridger (FP40); 0.6 m depth, made by a subsoiler coupled to a soil preparer mixing the soil to a depth of 0.6 m (FP60); 0.8 m depth, made by a subsoiler and, after mixing the soil to a depth of 0.6 m, by the soil preparer (FP80). The soil between the planting rows was covered by Brachiaria-grass. Soil sampling and field tests were performed in the coffee plants row mechanically treated, in the Brachiaria-grassed inter-row (IR) lane and in a nearby area under natural vegetation (NC). Treatments effects, either mechanical in the coffee rows (FP40, FP 60 and FP80), or biological in the inter-row lane (IR) were compared to reference (NC), representing soil conditions prior to coffee plantation. The FP60 and FP80 treatments improved water infiltration, storage and hydraulic conductivity in the planting rows to a depth of 0.5 m. A more favorable pore size distribution was obtained following these treatments, which improved the soil physical environment. Conversely, furrowing promoted compaction at each implement working depth due to the pressure applied by the rods in the subsurface soil layers, combined with subsoil moisture condition at the time of operations. Root activity of intercropped Brachiaria-grass (IR) improved soil structure, expressed by a favorable pore-size distribution and a faster hydraulic conductivity in the inter-row lane. Similar effects were obtained with FP 60 and FP80 for the coffee rows, where deep furrowing during soil preparation reduced the natural density of the Inceptisol. Therefore, the management strategies tested allowed root deepening and access to soil moisture stored in deeper layers.
Congenital syphilis (CS) is a major cause of mortality in several countries, especially in Latin America and the Caribbean. This study aimed to analyze fetal and infant mortality of CS reported to ...the Health Information System in a State in Northeastern Brazil.
This was a cross-sectional study that analyzed the deaths of CS from 2010 to 2014 through the linkage of the Mortality Information System (SIM) and the Notifiable Diseases Information System (Sinan). The Statistical Package for the Social Sciences (SPSS) version 23.0 was used to calculate the rates of Fetal, Perinatal, Neonatal (early and late), and Postneonatal Mortality. Simple linear regression was performed. Fisher's exact test or Pearson's chi-square test were used for comparison of proportions and Student's t-test was used for comparison of means. Of the 414 cases reported to the SIM as deaths possibly caused by CS, 44 (10.6%) presented CS as the underlying cause. From 2010 to 2014 the Infant Mortality Rate of CS was 16.3 per 100,000 live births (y = 0.65x + 14.33, R2 = 0.2338, p = 0.003). There was an 89.4% underreporting of deaths. Perinatal deaths and fetal deaths of CS accounted for 87.7% and 73.9% of total deaths, respectively.
The results of the study revealed a significant Fetal and Infant Mortality rate of CS and demonstrated the importance of using the linkage method in studies that involve the analysis of secondary data obtained from mortality and disease reporting systems. The underreporting of CS as a cause of fetal and infant mortality leads to unawareness of the reality of deaths from this disease, hindering the development of public policies aimed at its prevention.
Inappropriate processing and disposal of electronic waste contributes to the contamination of aquatic systems by various types of pollutants such as the rare-earth elements (REE) in which lanthanum ...(La) is included. Knowledge on the toxicity of these elements in marine organisms is still scarce when compared to other metals such as mercury (Hg) and arsenic (As). Therefore, this study aims to assess the toxicity of La on the mussel Mytilus galloprovincialis, considered a good bioindicator of aquatic pollution, through the analysis of metabolic, oxidative stress, neurotoxicity and histopathological markers. Organisms were exposed to different concentrations of La for a period of 28 days (0, 0.1, 1, 10 mg/L) under controlled temperature (18 °C ± 1.0) and salinity (30 ± 1) conditions. La concentrations in mussels increased in higher exposure concentrations. La exposure demonstrated a biochemical response in mussels, evidenced by lowered metabolism and accumulation of energy reserves, activation of the antioxidant defences SOD and GPx as well as the biotransformation enzymes GSTs, especially at intermediate concentrations. Despite oxidative stress being shown by a decrease in GSH/GSSG, oxidative damage was avoided as evidenced by lower LPO and PC levels. Inhibition of the enzyme AChE demonstrated the neurotoxicity of La in this species. Histopathological indices were significantly different from the control group, indicating impacts in gonads, gills and digestive glands of mussels due to La. These results show that La can be considered a risk for marine organisms and thus its discharge into the environment should be monitored.
The interest in the consequences of climate change on the physiological and biochemical functioning of marine organisms is increasing, but the indirect and interactive effects resulting from warming ...on bioconcentration and responsiveness to pollutants are still poorly explored, particularly in terms of cellular responses. The present study investigated the impacts of Hg in Mytilus galloprovincialis under control (17°C) and warming (21°C) conditions, assessing mussels Hg bioconcentration capacity, metabolic and oxidative status after 14 and 28days of exposure. Results obtained showed greater impacts in mussels exposed for 28days in comparison to 14days of exposure. Furthermore, our findings revealed that the increase in temperature from 17 to 21°C reduced the bioconcentration of Hg by M. galloprovincialis, which may explain higher mortality rates at 17°C in comparison to 21°C. Lower Hg concentration at 21°C in mussels tissue may result from valves closure for longer periods, identified by reduced energy reserves consumption at higher temperature, which in turn might also contributed to higher oxidative stress in organisms exposed to this condition. The highest LPO levels observed in mussels exposed to higher temperatures alone indicate that warming conditions will greatly affect M. galloprovincialis. Furthermore, the present study showed that the impacts induced by the combination of Hg and warming were similar to the ones caused by increased temperature acting alone, mainly due to increased antioxidant defenses in organisms under combined effects of Hg and warming, suggesting that warming was the factor that mostly contributed to oxidative stress in mussels. Although higher mortality was observed in individuals exposed to 17°C and Hg compared to organisms exposed to Hg at 21°C, the oxidative stress induced at higher temperature may generate negative consequences on mussels reproductive and feeding capacity, growth and, consequently, on population maintenance and dynamics.
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•Lower Hg accumulation was observed at higher temperatures.•Higher oxidative damage was induced by higher temperature.•Hg and warming decreased the metabolic capacity of Mytilus galloprovincialis.•Metabolic capacity decreased after 28days of exposure in comparison to 14days.•Cellular damage increased along the exposure period.
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•There are many challenges in the treatment of oral lesions, especially cancer.•Controlled release of imiquimod using polymeric films may avoid surgical resection.•The films showed ...mechanical and adhesion properties compatible with those required for oral use.•The films presented drug release values appropriate for oral use.
The immunomodulatory agent imiquimod (IQ) was incorporated in chitosan (Ch) and alginate (A) films aiming at developing a biomaterial to topically treat oral mucosal squamous cell carcinomas. IQ was directly added to either suspensions of the isolated polysaccharides or polyelectrolyte complexes formed by their mixture before film casting. The films presented incorporation efficiencies varying from 55 to 100%, and the highest values were attained for those containing chitosan. The addition of IQ generally increased film opacity and reduced fluid absorption by the films. The drug was released predominantly by diffusion in artificial saliva, resulting in releases of 1.49 to 2.76 μg of drug per mg of film, values considered as appropriate for oral use. Films of different formulations showed no significant differences concerning mucoadhesion properties, and thermogravimetric analysis demonstrated the occurrence of interactions between IQ, Ch, and A. The tensile strength of the films ranged from 16.43 to 64.17 MPa for those without IQ, and from 4.75 to 18.25 MPa for those with the drug, while elongation at break for all dried formulations did not exceed 4%. In conclusion, the films may have high potential as oral cancer therapeutic tools, replacing usual topical gels and creams, which are susceptible to leaching.
Infant mortality rate is a measure of population health and neonatal mortality account for great proportion of these deaths. Underdevelopment might be associated to higher neonatal mortality risk due ...to assistant related factors. Spatial and temporal distribution of mortality help identifying and developing strategies for interventions.
To investigate the cluster areas of asphyxia-associated neonatal mortality and to explore its association with per capita gross domestic product (GDP) in São Paulo State (SP), Brazil.
Ecological study including live births residents in SP from 2004-2013. Neonatal deaths (0-27 days) with perinatal asphyxia were defined as intrauterine hypoxia, birth asphyxia or meconium aspiration syndrome written in any line of the Death Certificate. Geoprocessing analytical approach included detection of first order effects through quintiles and spatial moving average maps, followed by second order effects by global and local spatial autocorrelation (Moran and LISA, respectively) before and after smoothing with local Bayesian estimates. Finally, Spearman correlation was applied between asphyxia-associated neonatal mortality and mean per capita GDP rates for the municipalities with significant LISA.
There were 6,713 asphyxia-associated neonatal deaths among 5,949,267 live births (rate: 1.13/1000) in SP. Spatial moving average maps showed a non-random distribution among municipalities, with presence of clusters (I = 0.048; p = 0.023). LISA map identified clusters of asphyxia-associated neonatal mortality in the south, southeast and northwest. After applying local Bayes estimates, clusters were more pronounced (I = 0.589; p = 0.001). There was a partial overlap of the areas of higher asphyxia-associated neonatal mortality and lower mean per capita GDP.
Spatial analysis identified cluster areas of high asphyxia-associated neonatal mortality and low per capita GDP rates, with a significant negative correlation. This optimized, structured, and hierarchical approach to identify high-risk areas of cause-specific neonatal mortality may be helpful for guiding public health efforts to decrease neonatal mortality.
Given their global importance, coastal marine environments are a major focus of concern regarding the potential impacts of climate change, namely due to alterations in seawater salinity. It is known ...that environmental characteristics, such as salinity, affect immune and physiological parameters of bivalves. Nevertheless, scarce information is available concerning the biochemical alterations associated with salinity changes. For this reason, the present work aimed to evaluate the biochemical responses of three venerid clam species (Venerupis decussata, Venerupis corrugata, Venerupis philippinarum) submitted to salinity changes. The effects on the native (V. decussata and V. corrugata) and invasive (V. philippinarum) species collected from the same sampling site and submitted to the same salinity gradient (0 to 42g/L) were compared. The results obtained demonstrated that V. corrugata is the most sensitive species to salinity changes and V. decussata is the species that can tolerate a wider range of salinities. Furthermore, our work showed that clams under salinity associated stress can alter their biochemical mechanisms, such as increasing their antioxidant defenses, to cope with the higher oxidative stress resulting from hypo and hypersaline conditions. Among the physiological and biochemical parameters analyzed (glycogen and protein content; lipid peroxidation levels, antioxidant enzymes activity; total, reduced and oxidized glutathione) Catalase (CAT) and especially superoxide dismutase (SOD) showed to be useful biomarkers to assess salinity impacts in clams.
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