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1.
Article in English | MEDLINE | ID: mdl-38935429

ABSTRACT

OBJECTIVE: While social cognition is shown to be impaired in several mental disorders, the effects of cannabis on social cognition are still not clear. Past studies have used the multifaceted empathy test (MET) to study social cognition. This study aims to test the validity of the MET Spanish version and to evaluate the effects of cannabis use on social cognition. METHODS: In total 116 participants from a Cannabis Social Club (CSC) completed the MET and the reading the mind in the eyes test (RMET) under the effects of cannabis and were compared to 86 university students (control group). Internal consistency and convergent validity were assessed. Cognitive empathy (CE) and emotional empathy (EE) were tested in both groups. RESULTS: The MET CE scale shows low internal consistency, while the EE scale shows high internal consistency. Items showed similar difficulty for both groups. Cannabis users showed deficient overall emotional recognition, with reduced scores associated with positive stimuli. Overall scores for EE were similar for both groups, but the experimental group scored lower with negative stimuli when compared to controls. CONCLUSION: This study validates the MET Spanish version for its use in future studies. Results confirmed deficient emotional recognition in cannabis users and a dampened reaction to negative stimuli for the first time.

2.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732094

ABSTRACT

This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it was traditionally thought that phosphate-calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases.


Subject(s)
Fibroblast Growth Factor-23 , Fibroblast Growth Factors , Phosphates , Humans , Fibroblast Growth Factor-23/metabolism , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/genetics , Animals , Phosphates/metabolism , Parathyroid Hormone/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Vitamin D/metabolism , Bone and Bones/metabolism , Klotho Proteins
3.
Clin Chem Lab Med ; 62(1): 128-137, 2024 01 26.
Article in English | MEDLINE | ID: mdl-37440753

ABSTRACT

OBJECTIVES: Since the prevalence of hypophosphatasia (HPP), a rare genetic disease, seems to be underestimated in clinical practice, in this study, a new diagnostic algorithm to identify missed cases of HPP was developed and implemented. METHODS: Analytical determinations recorded in the Clinical Analysis Unit of the Hospital Universitario Clínico San Cecilio in the period June 2018 - December 2020 were reviewed. A new clinical algorithm to detect HPP-misdiagnosed cases was used including the following steps: confirmation of persistent hypophosphatasemia, exclusion of secondary causes of hypophosphatasemia, determination of serum pyridoxal-5'-phosphate (PLP) and genetic study of ALPL gene. RESULTS: Twenty-four subjects were selected to participate in the study and genetic testing was carried out in 20 of them following clinical algorithm criteria. Eighty percent of patients was misdiagnosed with HPP following the current standard clinical practice. Extrapolating these results to the current Spanish population means that there could be up to 27,177 cases of undiagnosed HPP in Spain. In addition, we found a substantial proportion of HPP patients affected by other comorbidities, such as autoimmune diseases (∼40 %). CONCLUSIONS: This new algorithm was effective in detecting previously undiagnosed cases of HPP, which appears to be twice as prevalent as previously estimated for the European population. In the near future, our algorithm could be globally applied routinely in clinical practice to minimize the underdiagnosis of HPP. Additionally, some relevant findings, such as the high prevalence of autoimmune diseases in HPP-affected patients, should be investigated to better characterize this disorder.


Subject(s)
Autoimmune Diseases , Hypophosphatasia , Humans , Hypophosphatasia/diagnosis , Hypophosphatasia/epidemiology , Hypophosphatasia/complications , Alkaline Phosphatase , Genetic Testing , Mutation
4.
Cardiovasc Diabetol ; 22(1): 301, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37919715

ABSTRACT

BACKGROUND: Sclerostin is an inhibitor of the Wnt/b-catenin pathway, which regulates bone formation, and can be expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD) and increased serum and tissue expression of sclerostin. However, whether the role of sclerostin is detrimental or protective in the development of CVD is unknown. Therefore, our aims are to determine the level of sclerostin in T2D patients with/without CVD and in controls, both at serum and vascular tissue, and to analyze the role of sclerostin in VSMCs under calcified environments. METHODS: Cross-sectional study including 121 controls and 139 T2D patients with/without CVD (48/91). Sclerostin levels in serum were determined by ELISA, and sclerostin expression was analyzed by RT-qPCR and immunohistochemistry in calcified and non-calcified artery of lower limb from T2D patients (n = 7) and controls (n = 3). In vitro experiments were performed in VSMCs (mock and sclerostin overexpression) under calcifying conditions analyzing the sclerostin function by determination of calcium and phosphate concentrations, and quantification of calcium deposits by Alizarin Red. Proliferation and apoptosis were analyzed by MTT assay and flow cytometry, respectively. The regulation of the expression of genes involved in bone metabolism was determined by RT-qPCR. RESULTS: A significant increase in serum sclerostin levels in T2D patients with CVD compared to T2D patients without CVD and controls (p < 0.001) was observed. Moreover, higher circulating sclerostin levels were independently associated with CVD in T2D patients. Increased sclerostin expression was observed in calcified arteries of T2D patients compared to non-calcified arteries of controls (p = 0.003). In vitro experiments using VSMCs under calcified conditions, revealed that sclerostin overexpression reduced intracellular calcium (p = 0.001), calcium deposits (p < 0.001), cell proliferation (p < 0.001) and promoted cell survival (p = 0.015). Furthermore, sclerostin overexpression exhibited up-regulation of ALPL (p = 0.009), RUNX2 (p = 0.001) and COX2 (p = 0.003) and down-regulation of inflammatory genes, such as, IL1ß (p = 0.005), IL6 (p = 0.001) and IL8 (p = 0.003). CONCLUSIONS: Sclerostin could play a protective role in the development of atherosclerosis in T2D patients by reducing calcium deposits, decreasing proliferation and inflammation, and promoting cell survival in VSMCs under calcifying conditions. Therefore, considering the bone-vascular axis, treatment with anti-sclerostin for bone disease should be used with caution.


Subject(s)
Atherosclerosis , Diabetes Mellitus, Type 2 , Vascular Calcification , Humans , Muscle, Smooth, Vascular/metabolism , Calcium/metabolism , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Cross-Sectional Studies , Atherosclerosis/metabolism , Apoptosis , Cell Proliferation , Myocytes, Smooth Muscle/metabolism , Vascular Calcification/genetics , Cells, Cultured
5.
Am J Physiol Endocrinol Metab ; 325(5): E649-E660, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37819194

ABSTRACT

Osteoglycin, a fundamental proteoglycan within the vascular extracellular matrix, is expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with cardiovascular disease (CVD) but the role of osteoglycin in the development of CVD is controversial to date. Therefore, our aims are to determine and compare the level of osteoglycin in T2D patients with/without CVD versus control subjects both at serum and vascular tissue and to analyze in vitro role of osteoglycin in VSMCs under calcified conditions. For this, serum osteoglycin levels were determined by enzyme-linked immunosorbent assay (ELISA) in 117 controls and 129 patients with T2D (46 with CVD and 83 without CVD), revealing a significant increase in patients with T2D compared with controls. Osteoglycin level was not an estimator of CVD but correlated with markers of insulin resistance (triglycerides and triglycerides/high-density lipoprotein cholesterol index) in patients with T2D. At the vascular level, osteoglycin expression was assessed by RT-qPCR and immunohistochemistry, and no significant differences were observed between calcified arteries from patients with T2D and noncalcified arteries from controls. In vitro experiments using VSMCs (mock and overexpressing osteoglycin) under calcifying conditions were performed to analyze the osteoglycin function. The overexpression of osteoglycin in VMSCs under calcifying conditions revealed an increase of cell proliferation without effect on apoptosis and an upregulation of the expression of autotaxin (ATX) involved in inflammatory processes. In conclusion, osteoglycin could play a role in glycemic homeostasis, being a potential biomarker of insulin resistance in patients with T2D. Furthermore, osteoglycin could indirectly participate in the development of atherosclerosis through its regulatory effect on ATX and by proliferating VSMCs.NEW & NOTEWORTHY This study uncovers an increase of serum osteoglycin levels in patients with type 2 diabetes, which does not appear to be associated with the development of atherosclerosis, but rather with insulin resistance in this population. Overexpression of osteoglycin increased proliferation and upregulated the expression of autotaxin in vascular smooth muscle cells within calcified environments. Osteoglycin could be a biomarker of insulin resistance for type 2 diabetes and could be indirectly involved in the development of atherosclerosis.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Diabetes Mellitus, Type 2/metabolism , Muscle, Smooth, Vascular , Atherosclerosis/metabolism , Cardiovascular Diseases/metabolism , Biomarkers/metabolism , Triglycerides/metabolism , Myocytes, Smooth Muscle/metabolism
6.
Int J Mol Sci ; 24(4)2023 Feb 18.
Article in English | MEDLINE | ID: mdl-36835545

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) seems to have some molecular links with atherosclerosis (ATH); however, the molecular pathways which connect both pathologies remain unexplored to date. The identification of common factors is of great interest to explore some therapeutic strategies to improve the outcomes for those affected patients. Differentially expressed genes (DEGs) for NAFLD and ATH were extracted from the GSE89632 and GSE100927 datasets, and common up- and downregulated DEGs were identified. Subsequently, a protein-protein interaction (PPI) network based on the common DEGs was performed. Functional modules were identified, and the hub genes were extracted. Then, a Gene Ontology (GO) and pathway analysis of common DEGs was performed. DEGs analysis in NAFLD and ATH showed 21 genes that were regulated similarly in both pathologies. The common DEGs with high centrality scores were ADAMTS1 and CEBPA which appeared to be down- and up-regulated in both disorders, respectively. For the analysis of functional modules, two modules were identified. The first one was oriented to post-translational protein modification, where ADAMTS1 and ADAMTS4 were identified, and the second one mainly related to the immune response, where CSF3 was identified. These factors could be key proteins with an important role in the NAFLD/ATH axis.


Subject(s)
Atherosclerosis , Non-alcoholic Fatty Liver Disease , Humans , Atherosclerosis/genetics , Computational Biology , Gene Expression Profiling , Gene Regulatory Networks , Non-alcoholic Fatty Liver Disease/genetics , Protein Interaction Maps
7.
Front Endocrinol (Lausanne) ; 14: 1320516, 2023.
Article in English | MEDLINE | ID: mdl-38234425

ABSTRACT

Introduction: Hypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease. Methods: Patients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry. Results: Two previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction. Conclusions: The two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level.


Subject(s)
Hypophosphatasia , Humans , Hypophosphatasia/genetics , Hypophosphatasia/pathology , Alkaline Phosphatase , HEK293 Cells , Leukocytes, Mononuclear/metabolism , Mutation
8.
Int J Mol Sci ; 23(13)2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35805996

ABSTRACT

Vascular complications are the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). These vascular abnormalities result in a chronic hyperglycemic state, which influences many signaling molecular pathways that initially lead to increased oxidative stress, increased inflammation, and endothelial dysfunction, leading to both microvascular and macrovascular complications. Endothelial dysfunction represents the initial stage in both types of vascular complications; it represents "mandatory damage" in the development of microvascular complications and only "introductory damage" in the development of macrovascular complications. Increasing scientific evidence has revealed an important role of the Wnt pathway in the pathophysiology of the vascular wall. It is well known that the Wnt pathway is altered in patients with T2DM. This review aims to be an update of the current literature related to the Wnt pathway molecules that are altered in patients with T2DM, which may also be the cause of damage to the vasculature. Both microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, and peripheral arterial disease) are analyzed. This review aims to concisely concentrate all the evidence to facilitate the view on the vascular involvement of the Wnt pathway and its components by highlighting the importance of exploring possible therapeutic strategy for patients with T2DM who develop vascular pathologies.


Subject(s)
Cardiovascular Diseases , Cardiovascular System , Diabetes Complications , Diabetes Mellitus, Type 2 , Peripheral Arterial Disease , Diabetes Complications/complications , Diabetes Mellitus, Type 2/complications , Humans , Peripheral Arterial Disease/complications , Wnt Signaling Pathway
9.
Front Endocrinol (Lausanne) ; 13: 863940, 2022.
Article in English | MEDLINE | ID: mdl-35498405

ABSTRACT

Hypophosphatasia (HPP) a rare disease caused by mutations in the ALPL gene encoding for the tissue-nonspecific alkaline phosphatase protein (TNSALP), has been identified as a potentially under-diagnosed condition worldwide which may have higher prevalence than currently established. This is largely due to the overlapping of its symptomatology with that of other more frequent pathologies. Although HPP is usually associated with deficient bone mineralization, the high genetic variability of ALPL results in high clinical heterogeneity, which makes it difficult to establish a specific HPP symptomatology. In the present study, three variants of ALPL gene with uncertain significance and no previously described (p.Del Glu23_Lys24, p.Pro292Leu and p.His379Asn) were identified in heterozygosis in patients diagnosed with HPP. These variants were characterized at phenotypic, functional and structural levels. All genetic variants showed significantly lower in vitro ALP activity than the wild-type (WT) genotype (p-value <0.001). Structurally, p.His379Asn variant resulted in the loss of two Zn2+ binding sites in the protein dimer which may greatly affect ALP activity. In summary, we identified three novel ALPL gene mutations associated with adult HPP. The correct identification and characterization of new variants and the subsequent study of their phenotype will allow the establishment of genotype-phenotype relationships that facilitate the management of the disease as well as making it possible to individualize treatment for each specific patient. This would allow the therapeutic approach to HPP to be personalized according to the unique genetic characteristics and clinical manifestations of each patient.


Subject(s)
Hypophosphatasia , Alkaline Phosphatase/genetics , Genotype , Heterozygote , Humans , Hypophosphatasia/genetics , Phenotype
10.
Biomedicines ; 10(2)2022 Feb 06.
Article in English | MEDLINE | ID: mdl-35203598

ABSTRACT

The identification of common targets in Alzheimer's disease (AD) and cardiovascular disease (CVD) in recent years makes the study of the CVD/AD axis a research topic of great interest. Besides aging, other links between CVD and AD have been described, suggesting the existence of common molecular mechanisms. Our study aimed to identify common targets in the CVD/AD axis. For this purpose, genomic data from calcified and healthy femoral artery samples were used to identify differentially expressed genes (DEGs), which were used to generate a protein-protein interaction network, where a module related to AD was identified. This module was enriched with the functionally closest proteins and analyzed using different centrality algorithms to determine the main targets in the CVD/AD axis. Validation was performed by proteomic and data mining analyses. The proteins identified with an important role in both pathologies were apolipoprotein E and haptoglobin as DEGs, with a fold change about +2 and -2, in calcified femoral artery vs healthy artery, respectively, and clusterin and alpha-2-macroglobulin as close interactors that matched in our proteomic analysis. However, further studies are needed to elucidate the specific role of these proteins, and to evaluate its function as biomarkers or therapeutic targets.

12.
J Clin Med ; 10(10)2021 May 20.
Article in English | MEDLINE | ID: mdl-34065223

ABSTRACT

Osteoglycin (OGN) could be a biomarker of mild kidney function impairment in type 2 diabetes (T2D). Our study aimed to determine the association between serum OGN and impaired kidney function risk in T2D patients and to analyze its potential role as an estimator of kidney disturbances in this population. This cross-sectional study included 147 T2D patients (65 ± 8 years, 58.5% males), and 75 healthy controls (63 ± 10 years, 36% males). Circulating OGN levels were determined by ELISA. Linear regression modeling was performed to determine the variables influencing circulating OGN, and an ROC curve was plotted to assess the usefulness of OGN as an estimator of diabetic kidney disease risk. Circulating OGN was significantly increased in T2D patients compared to controls (18.41 (14.45-23.27) ng/mL vs. 8.74 (7.03-12.35) ng/mL; p < 0.001). We found a progressive increase in serum OGN according to the severity of kidney impairment in T2D patients (normal kidney function: 16.14 (12.13-20.48) ng/mL; mildly impaired kidney function: 19.15 (15.78-25.90) ng/mL; moderate impaired kidney function: 21.80 (15.06-29.22) ng/mL; p = 0.006). Circulating OGN was an independent estimator of mildly impaired kidney function risk in T2D patients. We suggest that serum OGN could act as an albuminuria-independent biomarker of incipient kidney dysfunction in T2D patients.

13.
PLoS One ; 16(3): e0249058, 2021.
Article in English | MEDLINE | ID: mdl-33730077

ABSTRACT

The petrochemical industry has made the economic development of many local communities possible, increasing employment opportunities and generating a complex network of closely-related secondary industries. However, it is known that petrochemical industries emit air pollutants, which have been related to different negative effects on mental health. In addition, many people around the world are being exposed to highly stressful situations deriving from the COVID-19 pandemic and the lockdowns adopted by national and regional governments. The present study aims to analyse the possible differential effects on various psychological outcomes (stress, anxiety, depression and emotional regulation strategies) stemming from the COVID-19 pandemic and consequent lockdown experienced by individuals living near an important petrochemical complex and subjects living in other areas, nonexposed to the characteristic environmental pollutants emitted by these kinds of complex. The sample consisted of 1607 subjects who answered an ad hoc questionnaire on lockdown conditions, the Perceived Stress Scale (PSS), the Hospital Anxiety and Depression Scale (HADS), the Barratt Impulsivity Scale (BIS) and the Emotional Regulation Questionnaire (ERQ). The results indicate that people living closer to petrochemical complexes reported greater risk perception [K = 73.42, p < 0.001, with a medium size effect (η2 = 0.061)]. However, no significant relationship between psychological variables and proximity to the focus was detected when comparing people living near to or far away from a chemical/petrochemical complex. Regarding the adverse psychological effects of the first lockdown due to COVID-19 on the general population in Catalonia, we can conclude that the conditions included in this survey were mainly related to changes in the participants' impulsivity levels, with different total impulsivity scores being obtained if they had minors in their care (p<0.001), if they had lost their jobs, if they were working (p<0.001), if they were not telecommuting (p<0.001), if they went out to work (p<0.001) or if they established routines (p = 0.009). However, we can also be fairly certain that the economic effects are going to be worse than those initially detected in this study. More research will be necessary to corroborate our results.


Subject(s)
COVID-19/psychology , Quarantine/psychology , Stress, Psychological/psychology , Adult , Anxiety/psychology , Anxiety Disorders/psychology , Depression/psychology , Female , Humans , Male , Mental Health , Pandemics/statistics & numerical data , Spain , Surveys and Questionnaires
14.
Sensors (Basel) ; 20(9)2020 Apr 29.
Article in English | MEDLINE | ID: mdl-32365580

ABSTRACT

This paper describes a simplified model and a generic model of high-frequency current transformer (HFCT) sensors. By analyzing the models, a universal charge estimation method based on the double time integral of the measured voltage is inferred. The method is demonstrated to be valid irrespective of HFCT sensor, assuming that its transfer function can be modelled as a combination of real zeros and poles. This paper describes the mathematical foundation of the method and its particularities when applied to measure nanosecond current pulses. In practice, the applicability of the method is subjected to the characteristics and frequency response of the sensor and the current pulse duration. Therefore, a proposal to use the double time integral or the simple time integral of the measured voltage is described depending upon the sensor response. The procedures used to obtain the respective calibration constants based on the frequency response of the HFCT sensors are explained. Two examples, one using a HFCT sensor with a broadband flat frequency response and another using a HFCT sensor with a non-flat frequency response, are presented.

15.
Sensors (Basel) ; 19(4)2019 Feb 19.
Article in English | MEDLINE | ID: mdl-30791413

ABSTRACT

This paper presents a new concept for partial discharge measurements in gas insulated systems (GIS). The proposed technique uses a novel GIS magnetic antenna that measures the magnetic field produced by partial discharges (PD) propagating in GIS. The foundations of the measurement technique and the magnetic antenna design are presented together with laboratory measurements. The magnetic antenna performance and the sensitivity of the acquisition system are studied. The bandwidth of the measurement system is in the high frequency and very high frequency (HF⁻VHF) range. Laboratory experiments demonstrate the suitability of the novel magnetic antenna-based measuring system for PD in GIS for corona, surface discharges, and free moving particles in SF6.

16.
Sensors (Basel) ; 18(12)2018 Dec 18.
Article in English | MEDLINE | ID: mdl-30567382

ABSTRACT

This paper presents a novel measuring system for partial discharge (PD) measurements in Gas Insulated Systems (GIS) using high frequency current transformers (HFCT). The system is based on the measurement of the induced PD currents in the GIS enclosure. In opposition to the existing antenna technologies that measure the radiated energy in the very high frequency/ultra-high frequency (VHF/UHF) range, the proposed system measures the PD conducted currents in the high frequency (HF) range and below. The foundation of the measurements together with a detailed explanation of the sensor installed conveniently at the bolts of the GIS spacer are presented. An experimental study on the current distribution in the GIS enclosure is described to evaluate the impact of the sensor on the measurements. Laboratory experiments have been performed that show the suitability of this method to properly measure particle discharges caused by corona, surface and free moving particle discharges in SF6. Discharges in the range of 1 to 4 pC have been properly measured. An analysis to evaluate the performance of the method is shown, in comparison to VHF/UHF antenna measurements. The potential benefits of this novel technique rely on the small attenuation of PD signals in the GIS components in the HF range and sample rate reductions. Finally, a discussion on the potential applicability of present cluster and charge calculation techniques to the proposed PD GIS measurement using HFCT is presented.

17.
Microchem J ; 141: 188-196, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30510325

ABSTRACT

Tin oxide, SnO2, nanomaterial was synthesized and tested for the removal of Cu2+ and Ni2+ ions from aqueous solutions. Various parameters for the binding were investigated in batch studied, which included pH, time, temperature, and interferences. In addition, isotherm studied were performed to determine the maximum binding capacity for both Cu2+ and Ni2+ ions. The optimal binding pH determined from the effects of pH were to be at pH 5 for both the Cu2+ and Ni2+ ions. The isotherm studies were performed at temperatures of 4°C, 25 °C, and 45 °C for both the Cu2+ and Ni2+ ions and were found to follow the Langmuir isotherm model. The binding capacities for the Cu2+ ions were 2.63 mg/g, 2.95 mg/g and 3.27 mg/g at the aforementioned temperatures, respectively. Whereas the binding capacities for Ni2+ were 0.79 mg/g, 1.07 mg/g, and 1.46 mg/g at the respective temperatures. The determined thermodynamic parameters for the binding showed that the binding processes for the reactions were endothermic, as the ΔG was observed to decrease with decreasing temperatures. As well the ΔH was 28.73 kJ/mol for Cu2+ (III) and 13.37 kJ/mol for Ni2+. The ΔS was observed to be 92.65 J/mol for Cu2+ and 54.53 J/mol for Ni2+. The free energy of adsorption for the Cu2+ was determined to be 13.99 kJ/mol and the activation energy for the binding of Ni2+ was determined to be 8.09 KJ/mol. The activation energy data indicate that the reaction was occurring through chemisorption.

18.
Cell ; 170(4): 800-814.e18, 2017 Aug 10.
Article in English | MEDLINE | ID: mdl-28802047

ABSTRACT

Improved methods for manipulating and analyzing gene function have provided a better understanding of how genes work during organ development and disease. Inducible functional genetic mosaics can be extraordinarily useful in the study of biological systems; however, this experimental approach is still rarely used in vertebrates. This is mainly due to technical difficulties in the assembly of large DNA constructs carrying multiple genes and regulatory elements and their targeting to the genome. In addition, mosaic phenotypic analysis, unlike classical single gene-function analysis, requires clear labeling and detection of multiple cell clones in the same tissue. Here, we describe several methods for the rapid generation of transgenic or gene-targeted mice and embryonic stem (ES) cell lines containing all the necessary elements for inducible, fluorescent, and functional genetic mosaic (ifgMosaic) analysis. This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution.


Subject(s)
Gene Targeting/methods , Animals , Cell Line , Embryonic Stem Cells , Mice , Mice, Transgenic
19.
Psychogeriatrics ; 17(1): 33-42, 2017 Jan.
Article in English | MEDLINE | ID: mdl-26817787

ABSTRACT

BACKGROUND: Cholinergic deficits play an important role in both cognitive and behavioural alterations in Alzheimer's disease. This study was aimed at evaluating the possible therapeutic role of PNU-282987 (PNU), an α7 nicotinic cholinergic receptor agonist, and the possible effects of stress in precipitating the onset of behavioural deficits in animals with susceptibility to Alzheimer's disease. METHODS: B6C3-Tg mice with susceptibility to Alzheimer's disease and wild-type mice either with or without restraint stress received 0- or 1-mg/kg PNU. At 12 months old, mice were evaluated for activity levels, anxiety-like levels, and spatial learning and memory. RESULTS: Data did not show the effects of PNU on activity and anxiety-like behaviour. No effect of PNU on acquisition of a spatial learning task was detected, but a reversal of stress effects on retention in the Morris water maze was observed in transgenic mice. CONCLUSIONS: Further studies are needed in order to better understand the role of α7 nicotinic cholinergic receptor agonists in motor activity, anxiety, and spatial learning and memory and to develop more accurate pharmacological treatment of psychopathological diseases.


Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/physiopathology , Benzamides/therapeutic use , Bridged Bicyclo Compounds/therapeutic use , Cognition/drug effects , Maze Learning/drug effects , Motor Activity/drug effects , Stress, Psychological/physiopathology , alpha7 Nicotinic Acetylcholine Receptor/agonists , Alzheimer Disease/psychology , Animals , Anxiety , Benzamides/pharmacology , Bridged Bicyclo Compounds/pharmacology , Disease Models, Animal , Male , Memory , Mice , Mice, Transgenic , Spatial Behavior/drug effects , Stress, Psychological/complications , alpha7 Nicotinic Acetylcholine Receptor/metabolism
20.
Food Chem Toxicol ; 97: 82-88, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27590783

ABSTRACT

Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation (137Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium (137Cs) (4000 and 8000 Bq/kg) and/or Nic (100 µg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137Cs.


Subject(s)
Anxiety/etiology , Behavior, Animal/drug effects , Brain/growth & development , Cesium Radioisotopes/toxicity , Motor Activity/physiology , Nicotine/toxicity , Spatial Memory/physiology , Adolescent , Adult , Animals , Anxiety/pathology , Brain/drug effects , Brain/radiation effects , Humans , Learning/drug effects , Learning/radiation effects , Male , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , Motor Activity/radiation effects , Nicotinic Agonists/toxicity , Radiation, Ionizing , Spatial Memory/drug effects , Spatial Memory/radiation effects
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