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1.
Phys Rev E ; 105(4-2): 045204, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35590536

ABSTRACT

A major development underlying hydrodynamic turbulence theory is the similarity decay hypothesis due to von Karman and Howarth, here extended empirically to plasma turbulence in the solar wind. In similarity decay the second-order correlation experiences a continuous transformation based on a universal functional form and a rescaling of energy and characteristic length. Solar wind turbulence follows many principles adapted from classical fluid turbulence, but previously this similarity property has not been examined explicitly. Here, we analyze an ensemble of Elsässer autocorrelation functions computed from Advanced Composition Explorer data at 1 astronomical unit (AU), and demonstrate explicitly that the two-point correlation functions undergo a collapse to a similarity form of the type anticipated from von Karman's hypothesis applied to weakly compressive magnetohydrodynamic turbulence. This provides a firm empirical basis for employing the similarity decay hypothesis to the Elsässer correlations that represent the incompressive turbulence cascade. This approach is of substantial utility in space turbulence data analysis, and for adopting von Karman-type heating rates in global and subgrid-scale dynamical modeling.

2.
Oxid Med Cell Longev ; 2020: 8819719, 2020.
Article in English | MEDLINE | ID: mdl-33204398

ABSTRACT

Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses produce carbonylation, glycation, glutathionylation, sulfhydration, nitration, and nitrosylation reactions. OS, RS, and NSS are interrelated since RS results from an overactivation of antioxidant systems and NSS is the result of the overactivation of the oxidation of nitric oxide (NO). Here, we discuss the general characteristics of the three types of stress and the way by which the reactions they induce (a) damage the DNA structure causing strand breaks or inducing the formation of 8-oxo-d guanosine; (b) modify histones; (c) modify the activities of the enzymes that determine the establishment of epigenetic cues such as DNA methyl transferases, histone methyl transferases, acetyltransferases, and deacetylases; (d) alter DNA reparation enzymes by posttranslational mechanisms; and (e) regulate the activities of intracellular enzymes participating in metabolic reactions and in signaling pathways through posttranslational modifications. Furthermore, the three types of stress may establish new epigenetic marks through these reactions. The development of cardiometabolic disorders in adult life may be programed since early stages of development by epigenetic cues which may be established or modified by OS, RS, and NSS. Therefore, the three types of stress participate importantly in mediating the impact of the early life environment on later health and heritability. Here, we discuss their impact on cardiometabolic diseases. The epigenetic modifications induced by these stresses depend on union and release of chemical residues on a DNA sequence and/or on amino acid residues in proteins, and therefore, they are reversible and potentially treatable.


Subject(s)
Cardiovascular Diseases/enzymology , Cardiovascular Diseases/genetics , Metabolic Diseases/enzymology , Metabolic Diseases/genetics , Nitrosative Stress/physiology , Oxidative Stress/physiology , Protein Processing, Post-Translational , Animals , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Epigenesis, Genetic , Humans , Metabolic Diseases/metabolism , Metabolic Diseases/pathology , Signal Transduction
3.
Int J Pharm ; 569: 118575, 2019 Oct 05.
Article in English | MEDLINE | ID: mdl-31356956

ABSTRACT

In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24 h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300 nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0 µg/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0 µg/ml and showed no toxicity up to 3.0 µg/ml Ofx in human cell models (A549 and Wi-38) at 24 h and 48 h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.


Subject(s)
Anti-Infective Agents , Drug Carriers , Eugenol , Nanoparticles , Ofloxacin , A549 Cells , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacokinetics , Cell Survival/drug effects , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Liberation , Eugenol/administration & dosage , Eugenol/chemistry , Eugenol/pharmacokinetics , Humans , Lipids/administration & dosage , Lipids/chemistry , Lipids/pharmacokinetics , Lung/metabolism , Mice , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Ofloxacin/administration & dosage , Ofloxacin/chemistry , Ofloxacin/pharmacokinetics , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development
4.
Clin Transl Oncol ; 21(8): 992-1004, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30644044

ABSTRACT

Harnessing the patient's own immune system against an established cancer has proven to be a successful strategy. Within the last years, several antibodies blocking critical "checkpoints" that control the activation of T cells, the immune cells able to kill cancer cells, have been approved for the use in patients with different tumours. Unfortunately, these cases remain a minority. Over the last years, radiotherapy has been reported as a means to turn a patient's own tumour into an in situ vaccine and generate anti-tumour T cells in patients who lack sufficient anti-tumour immunity. Indeed, review data show that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumour responses and improve the outcome of metastatic solid tumours. Here, we review the principal tumours where research in this field has led to new knowledge and where radioimmunotherapy becomes a reality.


Subject(s)
Neoplasms/therapy , Radioimmunotherapy/methods , Humans , Neoplasms/immunology , Neoplasms/pathology , Prognosis
5.
Colloids Surf B Biointerfaces ; 167: 73-81, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-29627680

ABSTRACT

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives for drug delivery to the central nervous system. In the present work, four different nanoformulations of the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogenization/ultrasonication method, with encapsulation efficiencies ranging from 82.8 to 93.8%. The formulations remained stable at 4 °C for at least 3 months. Physicochemical and microscopic characterization were performed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomic force microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shape nanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrapped CBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale model for spherical matrices and almost the 100% of the encapsulated drug was released in a controlled manner during the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayer model was similar to that of the free drug. In vivo experiments in a mice model of seizure suggested protection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The developed CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug release and possibly represent a promising tool to improve the treatment of refractory epilepsy linked to efflux transporters upregulation.


Subject(s)
Anticonvulsants/chemistry , Carbamazepine/chemistry , Lipids/chemistry , Nanoparticles/chemistry , Nanostructures/chemistry , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Calorimetry, Differential Scanning , Carbamazepine/administration & dosage , Carbamazepine/pharmacokinetics , Dogs , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation , Madin Darby Canine Kidney Cells , Mice , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Nanoparticles/ultrastructure , Nanostructures/ultrastructure , Particle Size , Thermogravimetry , X-Ray Diffraction
6.
Ann Oncol ; 29(5): 1312-1319, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29554212

ABSTRACT

Background: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. Patients and methods: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24 h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m2 was administered 1 week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating peripheral blood mononuclear cell (PBMCs) and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre- and post-treatment PBMC from patients achieving durable stable disease (SD) were studied by IFNγ ELISPOT-assays responding to tumor-lysate loaded DC and by TCRß sequencing. Results: Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+ immunotherapy. No objective responses were observed, while nine patients presented SD (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-ß and IFN-α mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1ß concentrations, especially in patients presenting SD. IFNγ-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD. Conclusions: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.


Subject(s)
Cancer Vaccines/administration & dosage , Immunotherapy/methods , Neoplasms/therapy , Radiosurgery/methods , Adult , Aged , Antigens, Neoplasm/administration & dosage , Antigens, Neoplasm/immunology , Cancer Vaccines/immunology , Carboxymethylcellulose Sodium/administration & dosage , Carboxymethylcellulose Sodium/analogs & derivatives , Combined Modality Therapy/methods , Cyclophosphamide/administration & dosage , Cytokines/immunology , Cytokines/metabolism , Dendritic Cells/immunology , Dendritic Cells/transplantation , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/immunology , Humans , Injections, Intralesional , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Neoplasms/immunology , Poly I-C/administration & dosage , Polylysine/administration & dosage , Polylysine/analogs & derivatives , Response Evaluation Criteria in Solid Tumors
7.
Ann Oncol ; 28(8): 1988-1995, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28595336

ABSTRACT

BACKGROUND: Surrogate biomarkers of efficacy are needed for anti-PD1/PD-L1 therapy, given the existence of delayed responses and pseudo-progressions. We evaluated changes in serum IL-8 levels as a biomarker of response to anti-PD-1 blockade in melanoma and non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Metastatic melanoma and NSCLC patients treated with nivolumab or pembrolizumab alone or nivolumab plus ipilimumab were studied. Serum was collected at baseline; at 2-4 weeks after the first dose; and at the time-points of response evaluation. Serum IL-8 levels were determined by sandwich ELISA. Changes in serum IL-8 levels were compared with the Wilcoxon test and their strength of association with response was assessed with the Mann-Whitney test. Accuracy of changes in IL-8 levels to predict response was estimated using receiver operation characteristics curves. RESULTS: Twenty-nine melanoma patients treated with nivolumab or pembrolizumab were studied. In responding patients, serum IL-8 levels significantly decreased between baseline and best response (P <0.001), and significantly increased upon progression (P =  0.004). In non-responders, IL-8 levels significantly increased between baseline and progression (P =  0.013). Early changes in serum IL-8 levels (2-4 weeks after treatment initiation) were strongly associated with response (P <0.001). These observations were validated in 19 NSCLC patients treated with nivolumab or pembrolizumab (P =  0.001), and in 15 melanoma patients treated with nivolumab plus ipilimumab (P <0.001). Early decreases in serum IL-8 levels were associated with longer overall survival in melanoma (P =  0.001) and NSCLC (P =  0.015) patients. Serum IL-8 levels also correctly reflected true response in three cancer patients presenting pseudoprogression. CONCLUSIONS: Changes in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/drug therapy , Interleukin-8/blood , Lung Neoplasms/drug therapy , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Antineoplastic Agents, Immunological/pharmacology , Carcinoma, Non-Small-Cell Lung/blood , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lung Neoplasms/blood , Male , Melanoma/blood , Middle Aged , Skin Neoplasms/blood , Survival Analysis
8.
J Mater Chem B ; 5(17): 3132-3144, 2017 May 07.
Article in English | MEDLINE | ID: mdl-32263711

ABSTRACT

Current medical treatments against recurrent pulmonary infections caused by Pseudomonas aeruginosa, such as cystic fibrosis (CF) disorder, involve the administration of inhalable antibiotics. The main challenge is, however, the eradication of microbial biofilms immersed in dense mucus that requires high and recurrent antibiotic doses. Accordingly, the development of novel drug delivery systems capable of providing local and controlled drug release in the lungs is a key factor to improve the therapeutic outcome of such therapeutic molecules. Inhalable hybrid carriers were prepared by co-precipitation of CaCO3 in the presence of alginate and the resulting microparticles were treated with alginate lyase (AL) in order to modify their porosity and enhance the drug loading. The hybrid microparticles were loaded with DNase (mucolytic agent) and levofloxacin (LV, wide-spectrum antibiotic) in the range of 20-40% for LV and 28-67% for DNase, depending on the AL treatment. In vitro studies demonstrated that microparticles were able to control the DNase release for 24 h, while 30-50% of LV was released in 3 days. The morphological characterization was performed by optical, fluorescence and scanning electron microscopies, showing a narrow size distribution (5 µm). FTIR, XRD, DSC and nitrogen adsorption isotherm studies revealed the presence of the drugs in a non-crystalline state. A microcidal effect of microparticles was found on P. aeruginosa in agar plates and corroborated by Live/Dead kit and TEM observations. Finally, to study whether the microparticles improved the localization of LV in the lungs, in vivo studies were performed by pulmonary administration of microparticles to healthy mice via nebulization and dry powder inhalation, followed by the quantification of LV in lung tissue. The results showed that microparticles loaded with LV delivered the antibiotic at least 3 times more efficiently than free LV. The developed system opens the gateway to new drug delivery systems that may provide enhanced therapeutic solutions against bacterial infections and in particular as a potential tool in CF pathology.

9.
Tumour Biol ; 37(10): 13687-13694, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27473086

ABSTRACT

Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Lung Neoplasms/pathology , Mutation/genetics , Protein Kinase Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/classification , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , DNA Mutational Analysis/methods , Drug Resistance, Neoplasm/genetics , Female , Follow-Up Studies , Humans , Lung Neoplasms/classification , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Middle Aged , Neoplasm Staging , Prognosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Survival Rate
10.
Transpl Infect Dis ; 18(3): 453-456, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27038417

ABSTRACT

The long-term use of left ventricular assist devices (LVADs) is becoming more common among the end-stage heart failure population. At the time of heart transplantation, most of the LVAD is removed, but some of its components might be retained. Retained LVAD prosthetic material can lead to serious infection post heart transplant. We report 4 such cases. Our goal is to highlight the importance of complete prosthetic material removal at the time of cardiac transplant to prevent late-onset infection, especially in patients with preceding infection, but also in patients without evidence of LVAD infection prior to orthotopic heart transplantation.

12.
Peptides ; 57: 101-8, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24819472

ABSTRACT

Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging.


Subject(s)
Angiotensin II/metabolism , Angiotensin I/metabolism , Metabolic Syndrome/genetics , Peptide Fragments/metabolism , Proto-Oncogene Proteins/biosynthesis , Receptor, Angiotensin, Type 2/biosynthesis , Receptors, Angiotensin/biosynthesis , Receptors, G-Protein-Coupled/biosynthesis , Adipose Tissue, White/metabolism , Aging/genetics , Aging/metabolism , Aging/pathology , Animals , Gene Expression Regulation , Humans , Hypertension/genetics , Hypertension/pathology , Metabolic Syndrome/metabolism , Metabolic Syndrome/pathology , Proto-Oncogene Mas , Rats , Renin-Angiotensin System/genetics
13.
J Dermatol Sci ; 72(2): 93-102, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23928229

ABSTRACT

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased. OBJECTIVE: To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis. METHODS: We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed. RESULTS: Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors. CONCLUSION: These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Lymphatic Metastasis , Skin Neoplasms/metabolism , Antigens, CD , Cadherins/metabolism , Down-Regulation , Homeodomain Proteins/metabolism , Humans , Immunohistochemistry , Membrane Glycoproteins/metabolism , Nuclear Proteins/metabolism , Phenotype , Retrospective Studies , Risk , Snail Family Transcription Factors , Transcription Factors/metabolism , Twist-Related Protein 1/metabolism , Vimentin/metabolism , Zinc Finger E-box-Binding Homeobox 1 , beta Catenin/metabolism
14.
Curr Med Chem ; 20(21): 2626-40, 2013.
Article in English | MEDLINE | ID: mdl-23590715

ABSTRACT

The definition of the Metabolic Syndrome (MS) has encountered difficulty in reaching a universal consensus although there exists an agreement of its main pathologies which are hypertension, obesity, dyslipidemia, insulin resistance, inflammation and renal damage. The prevalent opinion is that three of those alterations may define the syndrome. The incidence of the MS has increased globally, particularly in the last few years, to the point of being regarded as an epidemic. The treatment of the MS can be approached from different angles, since it may be a multifaceted health problem. A healthy lifestyle, which means the practice of regular exercise is suggested to MS patients. Increasing physical activity has anti-inflammatory effects since there is an inverse association of physical activity and inflammatory biomarker concentrations. An adequate diet is recommended, such as the Mediterranean, which contains fish, tomatoes, garlic, red peppers, olive oil and includes red wine, that is, antioxidants and non-saturated oils. There are also the traditional herbal preparations, used in the alternative medicine. Several therapeutic tools can be used; the most common are the pharmaceutical products to deal with obesity, hypertension, dyslipidemias, diabetes and inflammation. In addition several pharmacological therapies such as non steroidal anti-inflammatory drugs are recommended. Recently new mechanisms of action of statins, fibrates, metformin and thiazolidinediones have demonstrated their anti-inflammatory effect and potential use to treat MS.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Metabolic Syndrome/drug therapy , Plant Extracts/therapeutic use , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Humans , Molecular Structure , Plant Extracts/chemistry
15.
Mult Scler ; 19(2): 145-52, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22492129

ABSTRACT

A very high prevalence of multiple sclerosis (MS) has been reported in some Western European and North American countries. The few surveys of MS epidemiology in South America reveal lower prevalence rates, implying that susceptibility varies between distinct ethnic groups, thus forming an important determinant of the geographic distribution of the disease. The objective of this study is to review MS prevalence estimates in different Latin American and Caribbean countries. We reviewed surveys of regional MS prevalence from 1991 to 2011. Sources included an online database, authors' reports and proceedings or specific lectures from regional conferences. We obtained a total of 30 prevalence surveys from 15 countries, showing low/medium MS prevalence rates. Both the number and the quality of prevalence surveys have greatly improved in this region over recent decades. This is the first collaborative study to map the regional frequency of MS. Establishment of standardized methods and joint epidemiological studies will advance future MS research in Latin America and the Caribbean.


Subject(s)
Multiple Sclerosis/epidemiology , Caribbean Region/epidemiology , Data Collection , Disease Notification , Ethnicity , Geography , Humans , Latin America/epidemiology , Prevalence , South America/epidemiology , Ultraviolet Rays
16.
Arch. venez. farmacol. ter ; 30(1): 1-13, 2011. tab
Article in Spanish | LILACS | ID: lil-699593

ABSTRACT

El Consenso Venezolano de Enfermedad por Reflujo Gastroesófágico (ERGE) se realizó con el objeto de proveer guías para mejorar la identificación, el diagnóstico y el tratamiento de este trastorno en el país. Los coordinadores establecieron las líneas de consenso, basado en una revisión sistemática de la literatura médica de los últimos 15 años a partir de 1995. Participaron 55 miembros con el aval de sus respectivas cátedras y sociedades locales de gastroenterología. Éstos revisaron y presentaron los temas con sus niveles de evidencia y grados de recomendación para discutirlos y votarlos en una reunión plenaria. Tras un informe final de los miembros, los coordinadores prepararon las declaraciones finales. El consenso concluyó que la enfermedad por reflujo gastroesofágico tiene una prevalencia estimada del 11,54% en Venezuela, a predominio del sexo femenino (Grado B). El diagnóstico es fundamentalmente clínico, basado en la presencia de síntomas típicos y/o atípicos, e incluso síntomas de alarma que sugieren alguna complicación (Grado B). La endoscopia es importante en la investigación de la presencia de esofagitis de reflujo y laringitis de reflujo (Grado B). Las otras pruebas diagnósticas como lo son la pHmetría esofágica de 24 horas con o sin impedancia intraluminal multicanal son importantes en los pacientes que no tienen esofagitis, tienen síntomas atípicos o cuando hay falla en la respuesta al tratamiento médico (Grado B). La radiología, manometría esofágica y el ultrasonido endoscópico no están indicados en el diagnóstico de la ERGE (Grado B). El objetivo del tratamiento es reducir la exposición ácida en el esófago y con esto: aliviar los síntomas, cicatrizar las lesiones en la mucosa esofágica, prevenir la recurrencia y las complicaciones. Los inhibidores de bomba de protones deberían ser la primera opción en el tratamiento en el síndrome de ERGE y en la esofagitis por reflujo tanto en la fase aguda como durante el mantenimiento...


The Venezuelan Gastroesophageal Reflux Disease (GERD) Consensus was carried out in order to provide guidelines to improve the identification, diagnosis and treatment of this illness in Venezuela.  The coordinators established the consensuslines, based on a systematic revision of the medical literature of the last 15 years starting from 1995. 55 physicians participated with the support of their respective medical schools and local societies. They revised and presented the topics with their respective evidence levels and recommendation grades to discuss and vote them in a plenary meeting. After a final report of the members, the coordinators prepared the definitive declarations. The consensus concluded that GERD prevalence in Venezuela is 11,54%, higher in women than men (Grade B). The diagnosis is mainly clinical, based on the presence of typical and/or atypical symptoms and alarm symptoms that may suggest the presence of complications (Grade B). Endoscopy is important when reflux esophagitis and laryngitis are present (Grade B). Other diagnostic tests as ambulatory 24 hours pH monitoring with or without multichannel intraluminal impedance are important in patients without esophagitis, with atypical symptoms or when there is flaw in the answer to the medical treatment (Grade B). Radiology, esophageal manometry and endoscopic ultrasonography are not indicated in the diagnosis of GERD (Grade B). The objective of the treatment is to reduce the presence of acid in the esophagus and consequently: alleviate the symptoms and heal lesions in the esophagus mucosa to prevent recurrence and complications. Proton pump inhibitors should be the first option drug in the treatment of GERD syndrome andin esophagitis during the acute and the maintenance phase using standard or half dose (Grade A). So far, pokinetics are drugs with a limited use in GERD patients; they stimulate the esophagus/gastric motility...


Subject(s)
Humans , Proton Pump Inhibitors , Gastroesophageal Reflux/surgery , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/therapy , Education, Medical , Schools, Medical
17.
Behav Brain Res ; 207(2): 360-7, 2010 Mar 05.
Article in English | MEDLINE | ID: mdl-19857527

ABSTRACT

"Chinning" is a stereotyped scent marking behavior of domestic rabbits, in which the animal rubs the underside of its chin against objects in order to deposit scent gland secretions. Although the long-term maintenance of chinning requires circulating gonadal steroids, little is known about the acute regulation of this behavior. To define specific environmental stimuli that engage the chinning motor pattern, male rabbits were placed into an open field arena containing markable objects ("standard" bricks, "tall" bricks, or polished onyx spheres), observed for 30 min, returned to the home cage for 5 min, and then placed in the open field arena for another 30 min. During the 5 min interim: (1) the location of the open field or the spatial orientation of the objects within it were changed, (2) the olfactory or (3) visual characteristics of the objects were changed; or (4) no changes were made. Chinning and ambulation habituated to each type of object across the first 30 min, and bricks elicited more chinning than polished onyx spheres. In the second 30 min test, chinning was re-stimulated only when the original objects were replaced by visually different ones that had preferred characteristics. Ambulatory behavior was increased by changing the location of the open field arena, while modifying the olfactory characteristics of the objects had no effect on chinning or ambulation. These results indicate that scent marking is stimulated by object novelty and by the visual and/or tactile characteristics of the objects being marked.


Subject(s)
Behavior, Animal , Social Behavior , Touch Perception , Visual Perception , Animals , Environment , Female , Male , Motor Activity , Psychophysics , Rabbits , Recognition, Psychology , Time Factors
18.
Sci Total Environ ; 407(8): 2836-44, 2009 Apr 01.
Article in English | MEDLINE | ID: mdl-19185330

ABSTRACT

An interdisciplinary investigation, involving environmental geochemists, epidemiologists, nurses, and anthropologists, was undertaken to determine the contamination source and pathway of an on-going outbreak of lead poisoning among migrants originating from Zimatlán, Oaxaca, Mexico and living in Seaside, California, and among their US-born children. An initial investigation in Seaside identified grasshopper foodstuff ("chapulines") imported from Mexico and consumed as snacks, as containing alarmingly high lead concentrations (up to 2300 mg/kg). The focus in the present work concentrates on the Oaxacan area of origin of the problem in Mexico, and two potential sources of contamination were investigated: wind-borne dusts from existing mine residues as potential contaminants of soil, plant, and fauna; and food preparation practices using lead-glazed ceramic cookware. Over a three year period, sampling was conducted in Oaxaca using community-level sampling and also targeted sampling with families of cases with lead poisoning in California. In addition to fresh field chapulines, we analyzed for total lead: soil, water, mine residues, and plant materials, both from areas adjacent to or at an abandoned waste site containing mine tailings, and from fields where chapulines are collected; foodstuffs gathered in community markets or in a food transport business; and foodstuffs and cookware gathered from relatives of case families in California. Also, selected new and used lead-glazed clay cookware was extracted for lead, using 0.02 M citric acid and with 4% acetic acid. The results indicated significant presence of lead in mine wastes, in specific foodstuffs, and in glazed cookware, but no extensive soil contamination was identified. In-situ experiments demonstrated that lead incorporation in food is made very efficient through grinding of spices in glazed cookware, with the combination of a harsh mechanical action and the frequent presence of acidic lime juice, but without heating, resulting in high but variable levels of contamination.


Subject(s)
Ceramics/chemistry , Cooking and Eating Utensils , Environmental Monitoring , Food Contamination/analysis , Food Handling , Lead/analysis , Humans , Industrial Waste/analysis , Lead/chemistry , Mexico , Mining , Spices
19.
Article in Es | Desastres -Disasters- | ID: des-16404

ABSTRACT

Los deslizamientos originados por fuertes lluvias son comunes en Puerto Rico (PR). La presencia de pendientes empinadas en un terreno predominantemente montañoso, junto con suelos residuales e intensas lluvias conducen a graves problemas de estabilidad de taludes en la isla. El problema es agravado por eventos climáticos extremos como huracanes y terremotos. En la actualidad, todos los pueblos de la isla han sufrido algún tipo de deslizamiento. La estabilidad de taludes, naturales o artificiales, se ha vuelto una gran preocupación para las autoridades y la comunidad de ingenieros civiles en Puerto Rico. Este artículo presenta una revisión del problema de deslizamientos provocados por lluvias intensas en PR, una revisión de la literatura existente publicada acerca del tema y propone un umbral de intensidad- duración de lluvia a partir del cual pueden ocurrir deslizamientos basado en eventos registrados desde 1959 a 2003. Este umbral puede ser potencialmente usado como criterio de alerta a la población. (AU)


Subject(s)
Landslides , Rain , Puerto Rico , Topography , Geography , Climate Effects
20.
ScientificWorldJournal ; 2: 844-60, 2002 Mar 29.
Article in English | MEDLINE | ID: mdl-12806010

ABSTRACT

With the purpose of estimating the source contributions of nonmethane hydrocarbons (NMHC) to the atmosphere at three different sites in the Mexico City Metropolitan Area, 92 ambient air samples were measured from February 23 to March 22 of 1997. Light- and heavy-duty vehicular profiles were determined to differentiate the NMHC contribution of diesel and gasoline to the atmosphere. Food cooking source profiles were also determined for chemical mass balance receptor model application. Initial source contribution estimates were carried out to determine the adequate combination of source profiles and fitting species. Ambient samples of NMHC were apportioned to motor vehicle exhaust, gasoline vapor, handling and distribution of liquefied petroleum gas (LP gas), asphalt operations, painting operations, landfills, and food cooking. Both gasoline and diesel motor vehicle exhaust were the major NMHC contributors for all sites and times, with a percentage of up to 75%. The average motor vehicle exhaust contributions increased during the day. In contrast, LP gas contribution was higher during the morning than in the afternoon. Apportionment for the most abundant individual NMHC showed that the vehicular source is the major contributor to acetylene, ethylene, pentanes, n-hexane, toluene, and xylenes, while handling and distribution of LP gas was the major source contributor to propane and butanes. Comparison between CMB estimates of NMHC and the emission inventory showed a good agreement for vehicles, handling and distribution of LP gas, and painting operations; nevertheless, emissions from diesel exhaust and asphalt operations showed differences, and the results suggest that these emissions could be underestimated.


Subject(s)
Air Pollutants/analysis , Hydrocarbons/analysis , Models, Chemical , Cities , Cooking , Mexico , Vehicle Emissions/analysis
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