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BACKGROUND: Chronic exposure to arsenic is associated with cancer and hypertension. Growing evidence suggests that altered methylation in long interspersed nuclear element-1 (LINE-1) is involved in many types of disorders, including cardiovascular disease. Here we evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP). METHODS: A total of 236 subjects (175 from arsenic-endemic areas and 61 from a non-endemic area) in rural Bangladesh were recruited. The subjects' arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by inductively coupled plasma mass spectroscopy. The subjects' LINE-1 methylation levels were determined by pyrosequencing. RESULTS: The average LINE-1 methylation levels of the subjects living in the arsenic-endemic areas were significantly (p < 0.01) lower than those of the subjects living in the non-endemic area. In a sex-stratified analysis, the arsenic exposure levels in female but not male subjects showed a significant inverse association with LINE-1 methylation levels before (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) and after (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) adjustment for age, body mass index and smoking. Analyses examining interactions among arsenic levels, BP and LINE-1 methylation showed that arsenic-related elevated levels of BP were associated with LINE-1 hypomethylation. CONCLUSIONS: Our findings demonstrated that chronic exposure to arsenic was inversely associated with LINE-1 methylation levels in blood leukocyte DNA and this was more pronounced in females than males; in addition, the decreased levels of LINE-1 methylation might be involved in the arsenic-induced elevation of BP.
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Arsênio/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Elementos Nucleotídeos Longos e Dispersos/fisiologia , Poluentes Químicos da Água/efeitos adversos , Adulto , Arsênio/análise , Bangladesh , Estudos Transversais , Água Potável/análise , Exposição Ambiental/análise , Feminino , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Unhas/química , Poluentes Químicos da Água/análiseRESUMO
Elucidating the genetic, and neuronal bases for learned behavior is a central problem in neuroscience. A leading system for neurogenetic discovery is the vinegar fly Drosophila melanogaster; fly memory research has identified genes and circuits that mediate aversive and appetitive learning. However, methods to study adaptive food-seeking behavior in this animal have lagged decades behind rodent feeding analysis, largely due to the challenges presented by their small scale. There is currently no method to dynamically control flies' access to food. In rodents, protocols that use dynamic food delivery are a central element of experimental paradigms that date back to the influential work of Skinner. This method is still commonly used in the analysis of learning, memory, addiction, feeding, and many other subjects in experimental psychology. The difficulty of microscale food delivery means this is not a technique used in fly behavior. In the present manuscript we describe a microfluidic chip integrated with machine vision and automation to dynamically control defined liquid food presentations and sensory stimuli. Strikingly, repeated presentations of food at a fixed location produced improvements in path efficiency during food approach. This shows that improved path choice is a learned behavior. Active control of food availability using this microfluidic system is a valuable addition to the methods currently available for the analysis of learned feeding behavior in flies.
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Comportamento Animal/fisiologia , Pesquisa Comportamental/métodos , Drosophila/fisiologia , Aprendizagem Espacial/fisiologia , Animais , Percepção Auditiva/fisiologia , Drosophila melanogaster , Alimentos , Percepção Visual/fisiologiaRESUMO
Aflatoxins are important mycotoxins produced by Aspergillus flavus and A. parasiticus, moulds which contaminate mainly grains and nuts, especially in hot and humid climate. Presence of aflatoxin B1 (AFB1), the most toxic one and a potent hepatocarcinogen, has been reported in food and feed in Bangladesh and raised concerns about mycotoxin exposure in the population. Biomonitoring provides the best approach to assess human exposure from various sources and by all routes. Part of the ingested AFB1 is converted in the body to aflatoxin M1 (AFM1), a metabolite that has served as biomarker of AFB1 exposure, as it is excreted in urine, and thus enables non-invasive sampling, a relevant aspect in field studies. This investigation measured the AFM1 concentration in urines collected from adult residents of a rural (n = 52) and an urban (n = 43) area in the Rajshahi district of Bangladesh. The urinary levels of AFM1 were determined by enzyme-linked immunosorbent assay. AFM1 was detected in 46 % of all urine samples at a range of 31-348 pg/mL. The median and mean concentration of AFM1 in urine was 61 and 80 ± 60 pg/mL, respectively. A significant difference (p < 0.05) was found at the mean level of AFM1 between the rural (99 ± 71 pg/mL) and urban (54 ± 15 pg/mL) cohort. Urinary AFM1 levels did not show significant correlations with food frequency data or age, gender and body mass index of the participants. Among them, the highest mean AFM1 level (101 ± 71 pg/mL) was observed in the 50-60 years age group. In conclusion, detection frequency and urinary AFM1 levels in the Bangladeshi adults support concerns regarding their dietary exposure to AFB1. These first data warrant further biomarker-based studies in children and in cohorts of other parts of the country.
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Aflatoxina B1/análise , Aflatoxina M1/urina , Monitoramento Ambiental/métodos , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Adulto , Aflatoxina B1/metabolismo , Bangladesh , Biomarcadores/urina , Estudos de Coortes , Feminino , Contaminação de Alimentos/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estações do Ano , Clima Tropical , Adulto JovemRESUMO
Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p<0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose-response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs.
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Arsênio/toxicidade , Água Potável/efeitos adversos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Ácido Úrico/sangue , Poluentes Químicos da Água/toxicidade , Adolescente , Adulto , Arsênio/administração & dosagem , Intoxicação por Arsênico/sangue , Intoxicação por Arsênico/epidemiologia , Bangladesh/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Cabelo/química , Cabelo/efeitos dos fármacos , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Unhas/química , Unhas/efeitos dos fármacos , Poluentes Químicos da Água/administração & dosagem , Abastecimento de Água/normas , Adulto JovemRESUMO
Near-infrared (NIR) dyes have a unique ability to interact favorably with light in the NIR region, which is particularly interesting where stealth and camouflage are paramount, such as in military uniforms. Characterization of cotton fabric dyed with NIR-absorbing dyes using visible-NIR (Vis-NIR) and short-wave infrared (SWIR) hyperspectral imaging was done. The aim of the study was to discern spectral changes caused by variations in dye concentration and dyeing temperature as these parameters directly influence color- and crocking-fastness of fabrics impacting the camouflage effect. The fabric was dyed at three concentrations (2.5, 5, and 10%) and two dyeing temperatures (55 °C and 85 °C) and principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed on the spectra to discriminate the fabrics based on dye concentrations. The PCA models successfully segregated the fabrics based on the dye concentration and dyeing temperature, while PLS-DA models demonstrated classification accuracies between 75 and 100% in the Vis-NIR range. Spectra in the SWIR region could not be used to detect the differences in the concentrations of the NIR dyes. This finding is promising, as it aligns with the objective of creating NIR-dyed camouflage fabrics that remain indistinguishable under varying dye concentrations. These results open possibilities for further exploration in enhancing the stealth capabilities of textiles in military applications.
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INTRODUCTION AND IMPORTANCE: Hemolymphangioma, a rare type of lymphangioma, is a benign hamartoma of the blood vessels and lymphatic system. Considered to be extremely rare among adults with infrequent occurrence in abdominal regions, lymphangioma involving mesentery accounts for <1 % of cases and only 0.05 % involve the GI tract. Due to the absence of typical clinical presentation, making a confirmatory preoperative diagnosis is challenging. CASE PRESENTATION: An 18-year-old Bangladeshi man visited the hospital with the complaints of epigastric and umbilical pain for 15 days which was insidious in onset. Physical examination revealed an ill defined lump that was palpable on the right side of the abdomen. Ultrasonography showed multiloculated cystic mass having septation approximately 13 × 6 cm in size. An abdominal CT scan showed cystic lesion with septations measuring about 14.5 × 12.3 cm, compressing the bowel loops towards left, that was suggestive of mesenteric lymphangioma. The patient underwent partial surgical resection. The excised mass was sent for histopathology. Histopathology disclosed a benign tumor composed of proliferation of blood vessels of different sizes lined by endothelium in a fibromuscular stroma. CLINICAL DISCUSSION: Mesenteric lymphangiomas are infrequent malformations and very few cases of mesenteric hemolymphangioma have been reported in adults. Histopathology is required for confirmatory diagnosis and immunohistochemistry is required to differentiate the tumor subtype. Surgical resection is deemed a standard treatment modality. CONCLUSION: We report an extremely rare case of mesenteric hemolymphangioma to bring it to concern that even with the vague clinical presentations and involvement of age groups beyond the status quo, surgeons must be vigilant about abdominal MCL/hemolymphangioma and proceed accordingly.
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Background: The combination of empagliflozin and sitagliptin to treat type-2 diabetes might be more economical and patient compliance with an additive improvement in glycemic control due to complementary modes of action. Aim of the study: To design, formulate and optimize an immediate tablet dosage form containing empagliflozin and sitagliptin utilizing statistically reliable study design followed by in-vitro and in-vivo testing. Method: ology: To determine the effects of copovidone (X1) and croscarmellose sodium (X2) amounts on the dependent variables of disintegration time and percent drug release, the formulation was developed using Design Expert Software v.13's direct compression method-based central composite design optimization study. The formulations' assay, dissolution, friability, hardness, weight variation, disintegration, and anti-diabetic effects were evaluated in comparison to the standard drug. The analysis included the use of high performance liquid chromatography (HPLC) assay methods. Mice were employed to investigate the efficacy of an anti-diabetic drug after they were administered a high-fat diet and two injections of streptozotocin at a dosage of 30 mg/kg BW each. Results: Formulation of F3 out of nine had all in-vitro parameters at the most satisfactory condition. It was found that assay of the best formulation is 100.99% and 100.19% for empagliflozin and sitagliptin respectively. The disintegration time of F3 was found at 5.32 min. Percentage release of empagliflozin in 30 min was found 89.05% while sitagliptin was with 93.76%. The results showed that administration of F3 significantly reduced FBG (68.61%, p < 0.0001), total cholesterol levels (70.29 ± 0.48; p < 0.0001), triglycerides (70.20 ± 0.40, p < 0.0001); HDL levels (52.50 ± 0.31; p < 0.0001), LDL levels (33.34 ± 0.28; p < 0.0001), compared to diabetic control, this effect was comparable to metformin treatment. Conclusion: The direct compression approach has been used to develop, and optimize a new combination tablet incorporating empagliflozin and sitagliptin with better dissolution rate and anti-diabetic action.
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Gamma radiation has notable impacts on the flesh of mangoes. In this research, Katimon mangoes were subjected to different levels of irradiation (0.5, 1.0, 1.5, and 2.0 kGy) using a60Co irradiator. The results showed that irradiation significantly reduced the microbial population in the mango peels, with the 1.5 kGy dose showing the most significant reduction. Irradiation also delayed ripening and extended the shelf life of the mango peels. The total fat, protein, ash, moisture, and sugar content of the mango peels were all affected by irradiation. The total protein content, ash content and moisture content increased after irradiation, while the fat content remained relatively unchanged. The sugar content increased in all samples after storage, but the non-irradiated samples had higher sugar levels than the irradiated ones. The dietary fiber content of the mango peels was not significantly affected by irradiation. The vitamin C content decreased in all samples after storage. The titratable acidity and total soluble solids content of the mango peels increased after storage, but there were no significant differences between the irradiated and non-irradiated samples. Antioxidant activity and cytotoxicity assessment highlighted the antioxidant potential and reduced toxicity of irradiated samples. Additionally, the antimicrobial effectiveness of irradiated mango peels was evaluated. The most substantial inhibitory zones (measuring 16.90 ± 0.35) against Pseudomonas sp. were observed at a radiation dose of 1.5 kGy with 150 µg/disc. To identify potential antimicrobial agents, the volatile components of mangoes irradiated with 1.5 kGy were analyzed through GC-MS. Subsequently, these compounds were subjected to in silico studies against a viable protein, TgpA, of Pseudomonas sp. (PDB ID: 6G49). Based on molecular dynamic simulations and ADMET properties, (-)-Carvone (-6.2), p-Cymene (-6.1), and Acetic acid phenylmethyl ester (-6.1) were identified as promising compounds for controlling Pseudomonas sp.
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Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose-response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions.
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Intoxicação por Arsênico/sangue , Endotelina-1/sangue , Hipertensão/sangue , Hipertensão/induzido quimicamente , Dermatopatias/sangue , Dermatopatias/induzido quimicamente , Adolescente , Adulto , Arsênio/análise , Intoxicação por Arsênico/etiologia , Bangladesh , Feminino , Cabelo/química , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Unhas/química , Abastecimento de Água/análise , Adulto JovemRESUMO
The effect of extraction time, temperature, and alkali concentration on the physical and mechanical properties of cattail (Typha latifolia L.) fibres were investigated using five levels of time (4, 6, 8, 10, and 12 h), four levels of temperature (70, 80, 90, and 95 °C), and three levels of NaOH concentration (4, 7, 10%, w/v) in a 3 × 4 × 5 factorial experimental design. The extraction parameters were optimized for bio-composite application using a desirability function analysis (DFA), which determined that the optimum extraction time, temperature and NaOH concentration were 10 h, 90 °C, and 7%, respectively. A sensitivity analysis for optimal treatment conditions confirmed that the higher overall desirability does not necessarily mean a better solution. However, the analysis showed that the majority of optimum settings for time, temperature, and concentration of NaOH found in the sensitivity analysis matched with the optimum conditions determined by DFA, which confirmed the validity of the optimum treatment conditions.
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BACKGROUND: Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. METHODS: A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed. RESULTS: Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. CONCLUSIONS: The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.
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Intoxicação por Arsênico/sangue , Arsênio/análise , Testes de Função Hepática/métodos , Adulto , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Intoxicação por Arsênico/epidemiologia , Aspartato Aminotransferases/sangue , Bangladesh/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Cabelo/química , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Unhas/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/intoxicação , Abastecimento de Água/análiseRESUMO
Vacuum-assisted resin transfer molding (VARTM), used in manufacturing medium to large-sized composites for transportation industries, requires non-woven mats. While non-woven glass mats used in these applications are optimized for resin impregnation and properties, such optimized mats for natural fibers are not available. In the current research, cattail fibers were extracted from plants (18-30% yield) using alkali retting and non-woven cattail fiber mat was manufactured. The extracted fibers exhibited a normal distribution in diameter (d avg. = 32.1 µm); the modulus and strength varied inversely with diameter, and their average values were 19.1 GPa and 172.3 MPa, respectively. The cattail fiber composites were manufactured using non-woven mats, Stypol polyester resin, VARTM pressure (101 kPa) and compression molding pressures (260 and 560 kPa) and tested. Out-of-plane permeability changed with the fiber volume fraction (V f) of the mats, which was influenced by areal density, thickness, and fiber packing in the mat. The cattail fibers reinforced the Stypol resin significantly. The modulus and the strength increased with consolidation pressures due to the increase in V f, with maximum values of 7.4 GPa and 48 MPa, respectively, demonstrating the utility of cattail fibers from waste biomass as reinforcements.
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PURPOSE: The rate of alkaline hydrolysis of medical grade poly(ethylene terephthalate) of grey, scoured, and solvent extracted samples have been studied to understand their degradation behavior during surface modification which is used to produce antithrombus grafts. METHODS: The changes in properties were examined using weight loss, mechanical properties loss and infrared spectrum. RESULTS: It was found that the rate of hydrolysis of grey sample was always slower than the scoured, and solvent extracted samples. The slower rate of degradation of the grey polyester is attributed to the presence of spin finishes in the polyester biomaterials. Further, different scouring methods also gave samples with varying rates of hydrolysis. This is due to the different spin finish removal efficiency of different scouring procedures. The weight loss (%) of the solvent extracted samples were the largest which demonstrated that the solvent extraction technique is perhaps the best to remove spin finish from the polyester. CONCLUSIONS: Thus, these results serve as foundation for polyester biomaterials which are hydrolyzed before implantation in order to improve the protein binding capabilities to minimize thrombosis.
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Citrinin (CIT) is a mycotoxin contaminant in food commodities and can co-occur with ochratoxin A (OTA), another nephrotoxic contaminant in food and feed. Presence of OTA in maize from Bangladesh has been reported, but no data exist on CIT occurrence in food or feed in Bangladesh. Since biomonitoring provides the best approach to assess human exposure to contaminants from various sources and by all routes, a validated method for biomarker analysis has been used to investigate the presence of CIT and its metabolite dihydrocitrinone (HO-CIT) in urines from two Bangladeshi cohorts: Both analytes were determined in urine samples collected from inhabitants of a rural (n=32) and an urban (n=37) area in the Rajshahi district of Bangladesh. After cleanup by immunoaffinity columns, extracts were analyzed by LC-MS/MS; the limits of detection for CIT and HO-CIT in urine were 0.02 and 0.05 ng/mL, respectively. CIT and HO-CIT were detectable in 94 and 71% of all urine samples. Urinary biomarker levels did not show significant correlations with age, gender, and body mass index of the donors. However, excretion of CIT together with its metabolite HO-CIT was significantly higher (p<0.01) in the rural cohort (mean 1.1±1.9 ng/mL) than in the urban cohort (mean 0.14±0.14 ng/mL). This clearly indicates differences in mycotoxin exposure. As food habits differ between rural and urban people and also their main areas of occupation, further research is needed with regard to the major contributors of CIT exposure in the two cohorts. In conclusion, this first biomarker analysis indicates widespread and variable exposure to CIT in Bangladeshi adults.
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Biomarcadores/urina , Citrinina/urina , Urina/química , Adulto , Bangladesh , Cromatografia Líquida , Citrinina/análogos & derivados , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Espectrometria de Massas em Tandem , População Urbana , Adulto JovemRESUMO
Arsenic exposure is associated with cancer and vascular diseases. Angiogenesis is an important step for the pathological development of cancer and vascular diseases. Vascular endothelial growth factor (VEGF) is a specific marker for angiogenesis. However, human study showing the association between arsenic exposure and serum VEGF levels has not yet been documented. This study was aimed to investigate the association between arsenic exposure and serum VEGF levels in the arsenic-endemic individuals in Bangladesh. A total of 260 individuals were recruited for this study. Arsenic exposure levels were measured by ICP-MS and VEGF levels were quantified using VEGF immunoassay kit. The study subjects were stratified into tertile (low, medium and high) groups based on the arsenic in water, hair and nails. Serum VEGF levels were correlated with water (rs = 0.363, p < 0.001), hair (rs = 0.205, p < 0.01) and nail (rs = 0.190, p < 0.01) arsenic. Further, VEGF levels showed dose-response relationships with water, hair and nail arsenic. Mean VEGF levels in ⩽ 10 µg L(-1), 10.1-50 µg L(-1) and > 50 µg L(-1) groups were 91.84, 129.54, and 169.86 pg mL(-1), respectively, however, significant (p < 0.01) difference in VEGF levels was only found in > 50 µg L(-1) versus ⩽ 10 µg L(-1) groups. Significant associations of arsenic exposure with VEGF levels were found even after adjusting with relevant covariates. Therefore, these results provide evidence that arsenic exposure has a pro-angiogenic effect on humans, which may be implicated in arsenic-induced tumorigenesis and vascular diseases.
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Arsênio/análise , Água Potável/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo , Poluentes Químicos da Água/análise , Adolescente , Adulto , Arsênio/metabolismo , Bangladesh , Feminino , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Unhas/química , Poluentes Químicos da Água/metabolismo , Adulto JovemRESUMO
PURPOSE: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. METHODS: The binding of metoprolol succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis method (ED) at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. RESULTS: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 10(5) M(-1)) with low capacity (n1 = 2) and low affinity association (k2 = 4.0×10(5) M(-1)) constant with high capacity (n2 = 8) at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10(-5) M to 16×10(-5) M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. CONCLUSION: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.
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BACKGROUND: The habenula consists of an evolutionarily conserved set of nuclei that control neuromodulator release. In lower vertebrates, the dorsal habenula receives innervation from sensory regions, but the significance of this is unclear. Here, we address the role of the habenula in olfaction by imaging neural activity in larval zebrafish expressing GCaMP3 throughout the habenula and by carrying out behavioral assays. RESULTS: Activity in several hundred neurons throughout the habenula was recorded using wide-field fluorescence microscopy, fast focusing, and deconvolution. This enabled the creation of 4D maps of odor-evoked activity. Odors activated the habenula in two broad spatiotemporal patterns. Increasing concentrations of a putative social cue (a bile salt) evoked a corresponding increase in neuronal activity in the right dorsal habenula. In behavioral assays, fish were attracted to intermediate concentration of this cue but avoided higher concentration. Increasing cholinergic activity through nicotine exposure rendered the intermediate concentration aversive in a habenula-dependent manner. Pharmacologically blocking nicotinic receptors or lesioning the right dorsal habenula attenuated avoidance. CONCLUSIONS: These data provide physiological and functional evidence that the habenula functions as a higher center in zebrafish olfaction and suggest that activity in the right dorsal subdomain gates innate attraction to specific odors.
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Habenula/fisiologia , Núcleo Interpeduncular/fisiologia , Bulbo Olfatório/fisiologia , Olfato , Peixe-Zebra/fisiologia , Animais , Microscopia de Fluorescência , Motivação , OdorantesRESUMO
OBJECTIVE: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice. METHODS: Swiss albino male mice were divided into four groups. The first group was used as non-treated control group while, the second, third, and fourth groups were treated with M. oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice. RESULTS: It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol. CONCLUSIONS: The results indicate that the leaves of M. oleifera may be useful in reducing the effects of arsenic-induced toxicity.
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Elevated exposure to arsenic has been suggested to be associated with atherosclerosis leading to cardiovascular disease (CVD). However, biochemical events underlying the arsenic-induced atherosclerosis have not yet been fully documented. The aim of this study was to investigate the associations of circulating molecules involved in atherosclerosis with arsenic exposure in the individuals exposed to arsenic in Bangladesh. A total of 324 study subjects, 218 from arsenic-endemic areas and 106 from nonendemic areas in Bangladesh, were recruited. Drinking water, hair, nail, and blood samples were collected from the study subjects for analysis. Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were lower in arsenic-endemic subjects than those of nonendemic subjects. Oxidized LDL (Ox-LDL), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were significantly higher in arsenic-endemic subjects than those in nonendemic subjects. All these circulating molecules showed significant correlations with arsenic exposure (water, hair, and nail arsenic concentrations), and all these relations were significant before and after adjusting for relevant covariates. Among the circulating molecules tested in this study, HDL, Ox-LDL, and CRP showed dose-response relationships with arsenic exposure. Ox-LDL/HDL ratios were increased with the increasing concentrations of arsenic in the water, hair, and nails. Furthermore, non-HDL cholesterol and TC/HDL ratios were significantly correlated with arsenic exposure before and after adjusting for relevant covariates. Thus, all the observed associations may be the major features of arsenic exposure-related atherosclerosis leading to CVD.