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OBJECTIVE: To evaluate changes in choroidal thickness in presbyopes, when reading with regular glasses versus choroidal control glasses, in patients with or without Age-Related Macular Degeneration (AMD). METHODS: This was a pilot study on short-term axial length (AL) in 33 eyes of 24 presbyopic patients aged 60 to 80 years, assigned to two age-matched groups, with or without AMD. About them, changes in choroidal thickness were evaluated with ocular biometry through indirect measurements of axial length at baseline, after 20' of reading with conventional lenses, and after another 20' of reading with peripheral hyperopic defocus glasses. The differences in axial length between the three different times were analyzed. RESULTS: In presbyopes without AMD there was a significant axial length shortening of -13.44 microns in the first conventional reading period, which was reversed by 90% with hyperopic defocus lenses, recovering + 12.11 microns by axial lengthening (choroidal thinning, p = 0.03). In patients with AMD, axial shortening was significantly greater than controls, -23.86 microns with conventional lenses (p < 0.001) and they, also increased their axial length with defocus, although this response was smaller in proportion (+ 15.52 microns). CONCLUSION: Reading with positive lenses produces myopic defocus and choroidal thickening in presbyopes with and without AMD but was significantly greater in the latter. Glasses with Choroidal Control Technology reduced thickening during reading. KEY MESSAGES: What is known ⢠Presbyopia spectacles for near produce myopic defocus and choroidal thickening. What is new ⢠There are differences in choroidal thickening during reading between normal subjects and those with age related macular degeneration. ⢠Spectacles with Defocus Choroidal Control Technology reduce choroidal thickening during reading in presbyopes.
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Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the pro-inflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of the ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective effect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant.
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Acid mine drainage (AMD) causes major environmental problems and consequently, several treatments are proposed, favoring the passive systems because of their many advantages. The main goal of these procedures is the neutralization and removal of potentially toxic elements (PTE), yet little is known about the changes in the microbial assemblages in response to the hydrochemical variations during the treatments. Therefore, the main objective of this research was to determine the changes in the diversity and structure of the prokaryotic assemblages in a hybrid abiotic and biological (wetland) passive treatment system. The 16S rRNA gene survey showed that the AMD coming from the mine (pH 2.6) was mainly composed of acidophilic genera such as Acidithiobacillus, Leptospirillum, Ferritrophicum, and Cuniculiplasma (up to 76 % relative abundance). In the abiotic treatment, Acidiphilium was dominant in the sections with limestone filters (pH 2.2-4.8), followed by Limnobacter in the subsequent dolomite/limestone and phosphoric rock filters (pH 5.2-5.8). In these abiotic passive treatment sections, the microbial assemblage showed a limited diversity and richness. However, when the treated AMD reached the two final wetlands (pH ~6.8), the microbial diversity and richness increased, suggesting that further bioattenuation mechanisms might be occurring. Limnobacter and Novosphingobium were the main bacterial genera in the water samples of the wetland sections (Arundo donax). These changes in the composition of the microbial assemblages were highly correlated with the pH and Eh values during the treatment (p-value <0.001); however, the concentration of metal(loid)s such as Al, Cd, Fe, Mn, Ni, and Zn were also significantly related (p-value <0.05). In conclusion, the studied passive AMD treatment system enhanced the chemical quality of the treated AMD, showing high removal efficiencies for Al and Fe (> 99 %), and increasing the microbial diversity and richness in the effluent.
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Ácidos , Minería , Bacterias , Carbonato de Calcio , ARN Ribosómico 16S/genéticaRESUMEN
Introduction: Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries and one of the leading causes of blindness. In this work, we evaluated color vision and the pupil light reflex (PLR) to assess visual function in patients with early and neovascular AMD (NVAMD) compared with the control group. Methods: We recruited 34 early patients with dry AMD and classified them into two groups following AREDS: 13 patients with NVAMD and 24 healthy controls. Controls and patients with early dry AMD had visual acuity (VA) best or equal to 20/25 (0.098 logMAR). Color vision was assessed in controls and patients with early dry AMD using the Cambridge Color Test (CCT) 2.0 through the Trivector protocol. The PLR was evaluated using a Ganzfeld, controlled by the RETI-port system. The stimuli consisted of 1s blue (470 nm) and red (631 nm) light flashes presented alternately at 2-min intervals. To assess the cone contribution, we used a red flash at 2.4 log cd.m-2, with a blue background at 0.78 log cd.m-2. For rods, we used 470-nm flashes at -3 log cd.m-2, and for the melanopsin function of ipRGCs, we used 470 nm at 2.4 log cd.m-2. Results: Patients with early dry AMD had reduced color discrimination in all three axes: protan (p = 0.0087), deutan (p = 0.0180), and tritan (p = 0.0095) when compared with the control group. The PLR has also been affected in patients with early dry AMD and patients with NVAMD. The amplitude for the melanopsin-driven response was smaller in patients with early dry AMD (p = 0.0485) and NVAMD (p = 0.0035) than in the control group. The melanopsin function was lower in patients with NVAMD (p = 0.0290) than the control group. For the rod-driven response, the latency was lower in the NVAMD group (p = 0.0041) than in the control group. No changes were found in cone-driven responses between the control and AMD groups. Conclusion: Patients with early dry AMD present diffusely acquired color vision alteration detected by CCT. Rods and melanopsin contributions for PLR are affected in NVAMD. The CCT and the PLR may be considered sensitive tests to evaluate and monitor functional changes in patients with AMD.
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Acid mine drainage (AMD) is the major pollutant generated by the mining industry, and it is characterized by low pH and high concentration of metals and sulfate. The use of biochemical passive reactors (BPRs) is a promising strategy for its bioremediation. To date, there are various studies describing the taxonomical composition of BPR microbial communities, generally consisting of an assemblage of sulfate-reducing organisms inside Deltaproteobacteria, and a diverse set of anaerobic (ligno)cellulolytic bacteria; however, insights about its functional metagenomic content are still scarce. In previous studies, a laboratory-scale AMD bioremediation using biochemical passive reactors was designed and performed, tracking operation parameters, chemical composition, and changes, together with taxonomic composition of the microbiomes harbored in these systems. In order to reveal the main functional content of these communities, we used shotgun metagenomics analyses to explore genes of higher relative frequencies and their inferred functions during the AMD bioremediation from three BPRs representing the main microbiome compositions detected in the system. Remarkably, genes encoding for two-component regulatory systems and ABC transporters related to metal and inorganic ions, cellulose degradation enzymes, dicarboxylic acid production, and sulfite reduction complex were all detected at increased frequency. Our results evidenced that higher taxonomic diversity of the microbiome was arising together with a functional redundancy of the specific metabolic roles, indicating its co-selection and suggesting that its enrichment on BPRs may be implicated in the cumulative efficiency of these systems.
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Metagenómica , Minería , Ácidos , Biodegradación Ambiental , Sulfatos/metabolismoRESUMEN
Background: Age-related macular degeneration (AMD) is a multifactorial disease and one of the main causes of blindness in people over 50 years old. The etiology and pathophysiology of AMD are not well understood. The aim of this study was to investigate whether the rs1143627 variant allele of IL1B, which encodes Interleukin (IL)-1ß, a key cytokine, mediates immune and inflammatory responses.Methods: A case-control study was conducted with 397 AMD patients and 402 controls in Brazil. IL1B genotyping was carried out with TaqMan® genotyping assay. Differences in IL1B allele frequencies and genotypes were evaluated between patients and controls and between wet and dry subgroups of AMD. Relationships between allele presence/genotype and disease risk are reported as odds ratios (ORs) with 95% confidence intervals (CIs).Results: Genotype proportions for the rs1143627 variant allele of IL1B were similar between AMD patients and controls (p = .21), with 84.38% of AMD patients and 79.60% of the controls carrying the variant allele. We observed a trend toward the variant allele being associated with AMD risk (OR = 1.38, 95% CI 0.95-2.03, p = .08), as well as a trend toward the variant allele being associated with increased risk for wet AMD in particular (OR = 1.23, 95% CI 0.96-1.56, p = .08).Conclusions: The rs1443627 variant was not associated with AMD risk in this Brazilian population sample. Larger studies are warranted to determine whether the trends observed in this study reflect a relationship between this variant and risk of AMD, especially wet AMD.
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Interleucina-1beta/genética , Degeneración Macular/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Humanos , Degeneración Macular/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Oftalmoscopía , Factores de Riesgo , Microscopía con Lámpara de Hendidura , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
Extreme acidophiles thrive in environments rich in protons (pH values <3) and often high levels of dissolved heavy metals. They are distributed across the three domains of the Tree of Life including members of the Proteobacteria. The Acidithiobacillia class is formed by the neutrophilic genus Thermithiobacillus along with the extremely acidophilic genera Fervidacidithiobacillus, Igneacidithiobacillus, Ambacidithiobacillus, and Acidithiobacillus. Phylogenomic reconstruction revealed a division in the Acidithiobacillia class correlating with the different pH optima that suggested that the acidophilic genera evolved from an ancestral neutrophile within the Acidithiobacillia. Genes and mechanisms denominated as "first line of defense" were key to explaining the Acidithiobacillia acidophilic lifestyle including preventing proton influx that allows the cell to maintain a near-neutral cytoplasmic pH and differ from the neutrophilic Acidithiobacillia ancestors that lacked these systems. Additional differences between the neutrophilic and acidophilic Acidithiobacillia included the higher number of gene copies in the acidophilic genera coding for "second line of defense" systems that neutralize and/or expel protons from cell. Gain of genes such as hopanoid biosynthesis involved in membrane stabilization at low pH and the functional redundancy for generating an internal positive membrane potential revealed the transition from neutrophilic properties to a new acidophilic lifestyle by shaping the Acidithiobacillaceae genomic structure. The presence of a pool of accessory genes with functional redundancy provides the opportunity to "hedge bet" in rapidly changing acidic environments. Although a core of mechanisms for acid resistance was inherited vertically from an inferred neutrophilic ancestor, the majority of mechanisms, especially those potentially involved in resistance to extremely low pH, were obtained from other extreme acidophiles by horizontal gene transfer (HGT) events.
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Age-related macular degeneration (AMD) is among the world's leading causes of blindness. In its neovascular form (nAMD), around 25% of patients present further anatomical and visual deterioration due to persistence of neovascular activity, despite gold-standard treatment protocols using intravitreal anti-VEGF medications. Thus, to comprehend, the molecular pathways that drive choroidal neoangiogenesis, associated with the vascular endothelial growth factor (VEGF), are important steps to elucidate the mechanistic events underneath the disease development. This is a pilot study, a prospective, translational experiment, in a real-life context aiming to evaluate the protein profiles of the aqueous humor of 15 patients divided into three groups: group 1, composed of patients with nAMD, who demonstrated a good response to anti-VEGF intravitreal injections during follow-up (good responsive); group 2, composed of patients with anti-VEGF-resistant nAMD, who demonstrated choroidal neovascularization activity during follow-up (poor/non-responsive); and group 3, composed of control patients without systemic diseases or signs of retinopathy. For proteomic characterization of the groups, mass spectrometry (label-free LC-MS/MS) was used. A total of 2,336 proteins were identified, of which 185 were distinctly regulated and allowed the differentiation of the clinical conditions analyzed. Among those, 39 proteins, including some novel ones, were analyzed as potential disease effectors through their pathophysiological implications in lipid metabolism, oxidative stress, complement system, inflammatory pathways, and angiogenesis. So, this study suggests the participation of other promising biomarkers in neovascular AMD, in addition to the known VEGF.
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The evaporation of As-rich leachates generated by the weathering of sulfide-rich mine wastes accumulated in abandoned tailing dams of the La Concordia mine, triggers the widespread precipitation of saline crusts and efflorescences. Because these salts are highly soluble, they may release high concentrations of arsenic after rainfall events. Thus, the goal of this work is to assess the solid speciation of As in these efflorescences, which may help to understand the short-term cycling of As in the site. The results reveal that As is present only as As(V), while its capacity to be retained in the salts highly depends on their mineralogical composition. Hydrous sulfates, such as gypsum and epsomite show a very low capacity to scavenge As, while copiapite retains the highest concentrations of this element. The spectroscopic evidences suggest that in this mineral, As(V) is included within the lattice, substituting sulfate in the tetrahedral sites. Because copiapite is highly soluble, it may be considered as one of the most important transient reservoirs of As in the site that can release high concentrations of this hazardous pollutant during the occasional rainfall events produced during the wet season.
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BACKGROUND: AMD is becoming one of the leading causes of blindness in older adults. The prevalence rate of the wet form of AMD has been increasing due to the lack of selective therapeutic modalities. Current therapeutic interventions such as drugs targeting VEGF, and VEGF receptors, laser coagulants delivered unsuccessful clinical outcomes in AMD patients. Hence, the cost-effective anti-oxidant therapeutic interventions like molecular hydrogen to protect retinal pigment epithelium (RPE) by mitigating oxidative stress may deliver effective clinical outcomes in AMD patients. METHODS: Female patients with late-stage AMD of age above 70 years were chosen for this case report. The patients were administered QIAPI1©, a melanin precursor via sublingual route and the photographs were obtained for left and right eye to depict the efficacy of QIAPI1© against the wet form of AMD. RESULTS: The administration of QIAPI1© extensively mitigated yellow-colored drusen accumulations in the retina, retinal edema, exudates, and hemorrhages in the right eye, but the effect was minimal in the case of left eye; the overall drusen accumulation was lesser than the first consultation. CONCLUSION: Current case report has concluded the intrinsic effect of melanin in producing the molecular hydrogen and chemical energy across the retinal tissues by dissociating water molecules and dissipating the drusen accumulations, retinal edema, and hemorrhages in AMD patients. Our preliminary study reported the usage of QIAPI1© as a prospective therapeutic modality to mitigate the oxidative stress-mediated pathophysiology of the wet form of AMD.
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Degeneración Macular , Melaninas , Anciano , Femenino , Humanos , Degeneración Macular/tratamiento farmacológico , Retina , Epitelio Pigmentado de la RetinaRESUMEN
This work aimed to remove sulfate and acidity from mine-impacted water (MIW) via electrocoagulation (EC), a technique which stands as an advanced alternative to chemical coagulation in pollutant removal from wastewaters. The multiple electrochemical reactions occurring in the aluminum anode and the stainless steel cathode surfaces can form unstable flakes of metal hydroxysulfate complexes, causing coagulation, flocculation, and floatation; or, adsorption of sulfate on sorbents originated from the electrochemical process can occur, depending on pH value. Batch experiments in the continuous mode of exposition using different current densities (35, 50, and 65 A m-2) were tested, and a statistical difference between their sulfate removals was detected. Furthermore, the intermittent mode of exposure was also tested by performing a 22-factorial design to verify the combination with different current densities, concluding that better efficiencies of sulfate removal were obtained in the continuous mode of exposition, even with lower current densities. After 5 h of electrocoagulation, sulfate could be removed from MIW with a mean efficiency of 70.95% (in continuous mode of exposition and 65 A m-2 current density), and this sulfate removal follows probable third-order decay kinetics in accordance with the quick drop in sulfate concentration until 3 h of exposure time, remaining virtually constant at longer times. Graphical abstract.
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Contaminantes Químicos del Agua , Purificación del Agua , Aluminio , Electrocoagulación , Electrodos , Concentración de Iones de Hidrógeno , Cinética , Sulfatos , AguaRESUMEN
Organisms that thrive in extremely acidic environments (≤pH 3.5) are of widespread importance in industrial applications, environmental issues, and evolutionary studies. Leptospirillum spp. constitute the only extremely acidophilic microbes in the phylogenetically deep-rooted bacterial phylum Nitrospirae. Leptospirilli are Gram-negative, obligatory chemolithoautotrophic, aerobic, ferrous iron oxidizers. This paper predicts genes that Leptospirilli use to survive at low pH and infers their evolutionary trajectory. Phylogenetic and other bioinformatic approaches suggest that these genes can be classified into (i) "first line of defense", involved in the prevention of the entry of protons into the cell, and (ii) neutralization or expulsion of protons that enter the cell. The first line of defense includes potassium transporters, predicted to form an inside positive membrane potential, spermidines, hopanoids, and Slps (starvation-inducible outer membrane proteins). The "second line of defense" includes proton pumps and enzymes that consume protons. Maximum parsimony, clustering methods, and gene alignments are used to infer the evolutionary trajectory that potentially enabled the ancestral Leptospirillum to transition from a postulated circum-neutral pH environment to an extremely acidic one. The hypothesized trajectory includes gene gains/loss events driven extensively by horizontal gene transfer, gene duplications, gene mutations, and genomic rearrangements.
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Ácidos/toxicidad , Bacterias/genética , Genoma Bacteriano/genética , Genómica , Ácidos/metabolismo , Bacterias/metabolismo , Compuestos Férricos/metabolismo , Transferencia de Gen Horizontal/genética , Genoma Bacteriano/efectos de los fármacos , Concentración de Iones de Hidrógeno , Hierro/metabolismo , FilogeniaRESUMEN
BACKGROUND: Diabetic neuropathy is a common cause of painful diabetic neuropathy (PDN). C-X-C chemokine receptor type 4 (CXCR4) expression is increased in peripheral nerve samples from diabetes patients, suggesting a role for CXCR4 in PDN. Therefore, we evaluated the effects of Phα1ß, ω-conotoxin MVIIA, and AMD3100 in a model of streptozotocin (STZ)-induced PDN in rodents and naïve model of rats with the activation of the CXCR4/stromal cell-derived factor 1 (SDF-1) signal. METHODS: Diabetic neuropathy was induced by intraperitoneal (ip) injection of STZ in Wistar rats. Naïve rats were intrathecally injected with SDF-1 to test the CXCR4/SDF-1 signal. The effects of Phα1ß intrathecal (it), ω-conotoxin MVIIA intrathecal (it), and AMD3100 intraperitoneal (ip) on rat hypersensitivity, IL-6, and the intracellular calcium [Ca2+]i content of diabetic synaptosomes were studied. RESULTS: The drugs reduced the hypersensitivity in diabetic rats. SDF-1 (1.0 µg/it) administration in naïve rats induced hypersensitivity. Phα1ß (100 pmol/it) or AMD3100 (2.5 µg/ip) reduced this hypersensitivity after 2 h treatments, while ω-conotoxin MVIIA did not have an effect. IL-6 and [Ca2+]i content increased in the spinal cord synaptosomes in diabetic rats. The drug treatments reduced IL-6 and the calcium influx in diabetic synaptosomes. CONCLUSIONS: Phα1ß, ω-conotoxin MVIIA, and AMD3100, after 2 h of treatment of STZ-induced PDN, reduced hypersensitivity in diabetic rats. In naïve rats with CXCR4/SDF-1 activation, the induced hypersensitivity decreased after 2 h treatments with Phα1ß or AMD-3100, while ω-conotoxin MVIIA did not affect. The inhibitory effects of Phα1ß on PDN may involve voltage-dependent calcium channels.
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Analgésicos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Venenos de Araña/farmacología , Animales , Bencilaminas , Calcio/metabolismo , Canales de Calcio/metabolismo , Quimiocina CXCL12/metabolismo , Ciclamas , Diabetes Mellitus Experimental/complicaciones , Compuestos Heterocíclicos/farmacología , Ratas , Ratas Wistar , Receptores CXCR4/metabolismo , omega-Conotoxinas/farmacologíaRESUMEN
The Neotropical region harbors an astonishing diversity of species, but still encompasses the least studied biogeographic region of the world. These properties apply for different taxonomic groups, and can be exemplified by drosophilids. In fact, high levels of cryptic diversity have recently been discovered for Neotropical species of the Zygothrica genus group, but relationships among these species, or them and other Drosophilidae species still remains to be addressed. Therefore, the aim of this study was to evaluate the phylogenetic relationships between fungus-associated Neotropical species of the genera Hirtodrosophila, Mycodrosophila and Zygothrica, which together with Paramycodrosophila and Paraliodrosophila compose the Zygothrica genus group. For this, fragments of the mitochondrial cytochrome oxidase subunits I (COI) and II (COII) genes, and the nuclear alpha methyldopa (Amd) and dopa decarboxylase (Ddc) genes were newly characterized for 43 Neotropical specimens of fungus-associated drosophilids, and analyzed in the context of 51 additional Drosophilinae sequences plus one Steganinae outgroup. Based on the resulting phylogeny, the evolution of breeding sites usage was also evaluated through ancestral character reconstructions. Our results revealed the Zygothrica genus group as a monophyletic lineage of Drosophila that branches after the subgenera Sophophora and Drosophila. Within this lineage, Mycodrosophila species seem to encompass the early offshoot, followed by a grade of Hirtodrosophila species, with derived branches mostly occupied by representatives of Zygothrica. This genus, in particular, was subdivided into five major clades, two of which include species of Hirtodrosophila, whose generic status needs to be reevatuated. According to our results, the use of fungi as breeding sites encompasses a symplesiomorphy for the Zygothrica genus group, since one of the recovered clades is currently specialized in using flowers as breeding sites whereas a sole species presents a reversal to the use of fruits of a plant of Gentianales. So, in general, this study supports the paraphyly of Drosophila in relation to fungus-associated Neotropical species of Drosophilidae, providing the first molecular insights into the phylogenetic patterns related to the evolution of this diverse group of species and some of its characteristic traits.
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Drosophilidae/clasificación , Hongos/fisiología , Animales , Teorema de Bayes , Evolución Biológica , Cruzamiento , Núcleo Celular/genética , Dopa-Decarboxilasa/clasificación , Dopa-Decarboxilasa/genética , Drosophila/genética , Drosophilidae/genética , Drosophilidae/crecimiento & desarrollo , Complejo IV de Transporte de Electrones/clasificación , Complejo IV de Transporte de Electrones/genética , Mitocondrias/genética , FilogeniaRESUMEN
Background Diabetic neuropathy is a common cause of painful diabetic neuropathy (PDN). C-X-C chemokine receptor type 4 (CXCR4) expression is increased in peripheral nerve samples from diabetes patients, suggesting a role for CXCR4 in PDN. Therefore, we evaluated the effects of Pha1ß, Ômega-conotoxin MVIIA, and AMD3100 in a model of streptozotocin (STZ)-induced PDN in rodents and naïve model of rats with the activation of the CXCR4/stromal cell-derived factor 1 (SDF-1) signal. Methods Diabetic neuropathy was induced by intraperitoneal (ip) injection of STZ in Wistar rats. Naïve rats were intrathecally injected with SDF-1 to test the CXCR4/SDF-1 signal. The effects of Pha1ß intrathecal (it), Ômega-conotoxin MVIIA intrathecal (it), and AMD3100 intraperitoneal (ip) on rat hypersensitivity, IL-6, and the intracellular calcium [Ca2+]i content of diabetic synaptosomes were studied. Results The drugs reduced the hypersensitivity in diabetic rats. SDF-1 (1.0 µg/it) administration in naïve rats induced hypersensitivity. Pha1ß (100 pmol/it) or AMD3100 (2.5 µg/ip) reduced this hypersensitivity after 2 h treatments, while Ômega-conotoxin MVIIA did not have an effect. IL-6 and [Ca2+]i content increased in the spinal cord synaptosomes in diabetic rats. The drug treatments reduced IL-6 and the calcium influx in diabetic synaptosomes. Conclusions Pha1ß, Ômega-conotoxin MVIIA, and AMD3100, after 2 h of treatment of STZ-induced PDN, reduced hypersensitivity in diabetic rats. In naïve rats with CXCR4/SDF-1 activation, the induced hypersensitivity decreased after 2 h treatments with Pha1ß or AMD-3100, while Ômega-conotoxin MVIIA did not affect. The inhibitory effects of Pha1ß on PDN may involve voltage-dependent calcium channels.
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Acid mine drainage is one of the main environmental hazards to ecosystems worldwide and it is directly related to mining activities. In Ecuador, such acidic-metallic waters are drained to rivers without treatment. In this research, we tested a laboratory combined (Ca-Mg) Dispersed Alkaline Substrate (DAS) system as an alternative to remediate acid drainage from the Zaruma-Portovelo gold mining site, at El Oro, Ecuador. The system worked at low and high flow hydraulic rates during a period of 8 months, without signs of saturation.. Analysis of physico-chemical parameters and water composition (ICP-OES, ICP-MS) demonstrated that treatment effectively increased water pH and promoted the retention of about 80% of Fe, Al, Mn and Cu. Under acid conditions As, Cr and Pb concentrations decreased with Fe and possible precipitation of jarosite and schwertmannite. However, the homogeneous depletion of Cr at pH above 6 could be related to ferrihydrite or directly with Cr (OH)3 precipitation. After DAS-Ca, sulphate, phosphate and rare earth elements (REE) concentrations decreased to 1912, 0.85 and 0.07 mg/L respectively, while DAS-Mg contributed to form a complex model of minor carbonate and phosphate phases as main sink of REE. DAS-Mg also promoted the retention of most divalent metals at pH values over seven. Thus, this low cost treatment could avoid environmental pollution and international conflicts. Anyway, further investigations are needed to obtain higher Zn retention values. Graphical abstract.
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Monitoreo del Ambiente , Restauración y Remediación Ambiental/métodos , Minería , Modelos Químicos , Ácidos/análisis , Ecosistema , Ecuador , Compuestos Férricos , Compuestos de Hierro , Metales de Tierras Raras/análisis , Minerales/análisis , Ríos/química , Sulfatos , Contaminantes Químicos del Agua/análisisRESUMEN
This paper is focused on the hydrogeochemical characterization of the Negro River along its course, as well as in the proposal of a functioning model for the contamination processes in order to establish potential cause-effect relationships between water quality, geology (ARD), mining activities (AMD) and the tectonic framework as transmission vector of acidity, metals and sulphates. The scenario shows a heavily-contaminated river compared to the unaffected regional background. By graphical and statistical treatments of physico-chemical data of Negro River and the unaffected values of regional background and other AMD/ARD representative rivers' it is possible to conclude that Antamina Mine, is not the cause of the Negro River contamination, without the need of isotopic tracers, but just through the inexistent concentrations of Cu, Bi and Mo found in the waters. In the proposed contamination model, climatic factors (glacial retreat) activate geological (ARD) processes. The tectonic scenario (faults) intervenes as a transport medium of the contamination flux from the sulphide oxidation surface in upper altitudes until the spring in lower altitudes. At the end, it is concluded that this contamination comes from the recent glacial retreat in areas near the Cordillera Blanca that has left massive amounts of sulphide materials exposed to weathering conditions, oxidizing naturally (ARD processes) and finally contributing to the contamination of the Negro River through faults. In this case, we would face an ARD process in the strict sense, which is the direct oxidation of sulphides outcropping in the upper part of the mountain with the generation of sulphates, the release of hydrogen ions and the consequent generation of acid and the dissolution of the metals. This ARD process would come from the glacial retreat, which, through the faults, transports contaminated water until the spring.
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CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes-for instance, in the dystrophin-associated protein complex-might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4â»5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06â»3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03â»3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02â»0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.