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1.
Sci Total Environ ; 882: 163649, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37094676

RESUMO

The dumping of an estimated amount of 57 million tons of hazardous sulfide mine waste from 1957 to 1990 into Portmán's Bay (SE Spain) caused one of the most severe cases of persistent anthropogenic impact in Europe's costal and marine environments. The resulting mine tailings deposit completely infilled Portmán's Bay and extended seawards on the continental shelf, bearing high levels of metals and As. The present work, where Synchrotron XAS, XRF core scanner and other data are combined, reveals the simultaneous presence of arsenopyrite (FeAsS), scorodite (FeAsO4·2H2O), orpiment (As2S3) and realgar (AsS) in the submarine extension of the mine tailings deposit. In addition to arsenopyrite weathering and scorodite formation, the, the presence of realgar and orpiment is discussed, considering both potential sourcing from the exploited ores and in situ precipitation from a combination of inorganic and biologically mediated geochemical processes. Whereas the formation of scorodite relates to the oxidation of arsenopyrite, we hypothesize that the presence of orpiment and realgar is associated to scorodite dissolution and subsequent precipitation of these two minerals within the mine tailings deposit under moderately reducing conditions. The occurrence of organic debris and reduced organic sulfur compounds evidences the activity of sulfate-reducing bacteria (SRB) and provides a plausible explanation to the reactions leading to the formation of authigenic realgar and orpiment. The precipitation of these two minerals in the mine tailings, according to our hypothesis, has important consequences for As mobility since this process would reduce the release of As into the surrounding environment. Our work provides for the first time valuable hints on As speciation in a massive submarine sulfide mine tailings deposit, which is highly relevant for similar situations worldwide.

2.
Sci Total Environ ; 717: 134778, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843305

RESUMO

X-ray fluorescence core scanners (XRF-CS) allow rapid, non-destructive, continuous and high-resolution analyses of the elemental composition of sediment cores, providing large sets of semi-quantitative data. These data can be converted to quantitative data through the linear regression approach using a relatively small number of discrete samples analyzed by techniques providing absolute concentrations. However, a precise characterization of the errors associated with the linear function is required to evaluate the quality of the calibrated element concentrations. Here we present a calibration of high-resolution XRF-CS for six metals (Ti, Mn, Fe, Zn, Pb and As) measured in heavily contaminated marine deposits so that absolute concentrations are obtained. In order to determine the best linear function for conversion of XRF data, we have tested three regression methods: the ordinary least-squares (OLS), which does not consider the standard error in any variable (x and y), the weighted ordinary least-squares (WOLS), which considers the weighted standard error of the vertical variable (y), and the weighted least-squares (WLS), which incorporates the standard error in both x and y variables. We demonstrate that the calibration method presented in this study significantly increases the correlation coefficient, higher than r2 = 0.94, and reduces both the data deviation and the errors of the linear function for the three regression methods. Nonetheless, the WLS appears as the best regression method to minimize errors in the calibrated element concentrations. Our results open the door to use calibrated XRF-CS data to evaluate marine sediment pollution according to the levels of the strictest sediment quality guidelines (SQG) with errors lower than 0.4%-2% for Fe, 1%-7% for Zn, 3-14% for Pb and 5%-16% for Mn. They highlight the robustness of the calibration procedure here presented for accurate and precise quantification of element concentrations from XRF-CS semi-quantitative data.

3.
Med Vet Entomol ; 30(4): 383-391, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27424870

RESUMO

In Chile, all necrotic arachnidism is attributed to the Chilean recluse spider Loxosceles laeta (Nicolet) (Araneae: Sicariidae). It is predated by the spitting spider Scytodes globula (Nicolet) (Araneae: Scytodidae). The biology of each of these species is not well known and it is important to clarify their distributions. The aims of this study are to elucidate the variables involved in the niches of both species based on environmental and human footprint variables, and to construct geographic maps that will be useful in estimating potential distributions and in defining a map of estimated risk for loxoscelism in Chile. Loxosceles laeta was found to be associated with high temperatures and low rates of precipitation, whereas although S. globula was also associated with high temperatures, its distribution was associated with a higher level of precipitation. The main variable associated with the distribution of L. laeta was the human footprint (48.6%), which suggests that this is a highly invasive species. Similarly to other species, the distribution of L. laeta reaches its southern limit at the Los Lagos region in Chile, which coincides with high levels of precipitation and low temperatures. The potential distribution of L. laeta in Chile corresponds to the distribution of cases of loxoscelism.


Assuntos
Distribuição Animal , Ecossistema , Picaduras de Aranhas/epidemiologia , Aranhas/fisiologia , Animais , Chile/epidemiologia , Cadeia Alimentar , Humanos , Espécies Introduzidas , Chuva , Risco , Especificidade da Espécie , Picaduras de Aranhas/etiologia , Temperatura
4.
Med. Vet. Entomol ; 30(4): p. 383-391, 2016.
Artigo | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib14145

RESUMO

In Chile, all necrotic arachnidism is attributed to the Chilean recluse spider Loxosceles laeta (Nicolet) (Araneae: Sicariidae). It is predated by the spitting spider Scytodes globula (Nicolet) (Araneae: Scytodidae). The biology of each of these species is not well known and it is important to clarify their distributions. The aims of this study are to elucidate the variables involved in the niches of both species based on environmental and human footprint variables, and to construct geographic maps that will be useful in estimating potential distributions and in defining a map of estimated risk for loxoscelism in Chile. Loxosceles laeta was found to be associated with high temperatures and low rates of precipitation, whereas although S.globula was also associated with high temperatures, its distribution was associated with a higher level of precipitation. The main variable associated with the distribution of L.laeta was the human footprint (48.6%), which suggests that this is a highly invasive species. Similarly to other species, the distribution of L.laeta reaches its southern limit at the Los Lagos region in Chile, which coincides with high levels of precipitation and low temperatures. The potential distribution of L.laeta in Chile corresponds to the distribution of cases of loxoscelism


Assuntos
Entomologia
5.
Proc Biol Sci ; 282(1818): 20150587, 2015 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-26511045

RESUMO

Ocean acidification is receiving increasing attention because of its potential to affect marine ecosystems. Rare CO2 vents offer a unique opportunity to investigate the response of benthic ecosystems to acidification. However, the benthic habitats investigated so far are mainly found at very shallow water (less than or equal to 5 m depth) and therefore are not representative of the broad range of continental shelf habitats. Here, we show that a decrease from pH 8.1 to 7.9 observed in a CO2 vent system at 40 m depth leads to a dramatic shift in highly diverse and structurally complex habitats. Forests of the kelp Laminaria rodriguezii usually found at larger depths (greater than 65 m) replace the otherwise dominant habitats (i.e. coralligenous outcrops and rhodolith beds), which are mainly characterized by calcifying organisms. Only the aragonite-calcifying algae are able to survive in acidified waters, while high-magnesium-calcite organisms are almost completely absent. Although a long-term survey of the venting area would be necessary to fully understand the effects of the variability of pH and other carbonate parameters over the structure and functioning of the investigated mesophotic habitats, our results suggest that in addition of significant changes at species level, moderate ocean acidification may entail major shifts in the distribution and dominance of key benthic ecosystems at regional scale, which could have broad ecological and socio-economic implications.


Assuntos
Dióxido de Carbono/farmacologia , Ecossistema , Água do Mar/química , Ácidos/química , Animais , Antozoários/fisiologia , Briozoários/fisiologia , Carbonatos/química , Concentração de Íons de Hidrogênio , Laminaria/fisiologia , Mar Mediterrâneo , Rodófitas/fisiologia
6.
Enferm. intensiva (Ed. impr.) ; 26(2): 54-62, abr.-jun. 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-141128

RESUMO

Introducción: La infección del tracto urinario (ITU) asociada al sondaje uretral representa la segunda causa de infección nosocomial en Unidades de Cuidados Intensivos. Definimos ITU cuando obtenemos un resultado de 100.000 UFC/ml con al menos un microorganismo en el cultivo de orina. Objetivo principal: Determinar y comparar la incidencia de ITU en los pacientes postoperados de cirugía cardiaca según el dispositivo de sondaje. Material y método: Estudio observacional, analítico y prospectivo aleatorizado de pacientes en el postoperatorio inmediato de cirugía cardiaca. Un grupo fue sondado con sonda Foley y otro llevaba insertado el catéter BIPFoley-Bactiguard® (SBF). La SBF está recubierta de metales nobles (plata, oro y paladio) con propiedades antimicrobianas y biocompatible, que recubre toda la superficie del dispositivo y evita la formación de biofilm, la adherencia microbiana y la colonización. Resultados: Ciento dieciséis casos, el 59,5% (69 casos) han sido negativos para ITU y el 40,5% (47 casos) han sido positivos. De las ITU obtenidas el 25% eran portadores de sonda Foley y el 15,5% de SBF. Los microorganismos etiológicos más frecuentes son: Escherichia coli 29,8%, Klebsiella pneumoniae29,8% y Klebsiella oxytoca 9%.ConclusiónCon los datos obtenidos hemos observado una menor tasa de infección en los pacientes portadores de sonda BIPfoley-Bactiguard(R) en comparación con los pacientes portadores de sonda Foley


Introduction: Urinary tract infections (UTI) associated with urethral catheterization are the second cause of nosocomial infections in Intensive care units. We confirm a UTI when we get a result of 100,000 CFU/ml with at least one microorganism in a urine culture. Main objective: Compare and determine the incidence of UTI in cardiac surgery postpoperative patients according to the catheterization device. Methods: A prospective, randomized analytical observational study of patients in the immediate cardiac surgery postoperative period. One group was probed with catheter Foley and one was inserted the catheter BIPFoley-Bactiguard® (CBF). The CBF is coated with noble metals (silver, gold and palladium) and biocompatible antimicrobial properties, covering the entire surface of the device and prevents the formation of biofilm, microbial adherence and colonization. Results: 116 cases, 59.5% (69 cases) were negative for UTI and 40.5% (47 cases) were positive. Out of the positive UTI results, 25% were carriers of catheter Foley and 15.5% of CBF. Most common etiologic microorganisms: Escherichia coli 29.8% Klebsiella pneumonia 29.8%, Klebsiella oxytoca 9%.ConclusionWith the data we have observed that patients catheterized BIPfoley-Bactiguard(R) are infected to a lesser extent than Foley carriers


Assuntos
Humanos , Infecções Urinárias/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Cuidados Críticos/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Cateterismo Urinário/estatística & dados numéricos
7.
Mar Pollut Bull ; 95(1): 28-39, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25892079

RESUMO

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais/métodos , Ecossistema , Política Ambiental , Oceanos e Mares , Monitoramento Ambiental/métodos , Europa (Continente) , Pressão
8.
Enferm Intensiva ; 26(2): 54-62, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-25804335

RESUMO

INTRODUCTION: Urinary tract infections (UTI) associated with urethral catheterization are the second cause of nosocomial infections in Intensive care units. We confirm a UTI when we get a result of 100,000 CFU/ml with at least one microorganism in a urine culture. MAIN OBJECTIVE: Compare and determine the incidence of UTI in cardiac surgery postpoperative patients according to the catheterization device. METHODS: A prospective, randomized analytical observational study of patients in the immediate cardiac surgery postoperative period. One group was probed with catheter Foley and one was inserted the catheter BIPFoley-Bactiguard® (CBF). The CBF is coated with noble metals (silver, gold and palladium) and biocompatible antimicrobial properties, covering the entire surface of the device and prevents the formation of biofilm, microbial adherence and colonization. RESULTS: 116 cases, 59.5% (69 cases) were negative for UTI and 40.5% (47 cases) were positive. Out of the positive UTI results, 25% were carriers of catheter Foley and 15.5% of CBF. Most common etiologic microorganisms: Escherichia coli 29.8% Klebsiella pneumonia 29.8%, Klebsiella oxytoca 9%. CONCLUSION: With the data we have observed that patients catheterized BIPfoley-Bactiguard® are infected to a lesser extent than Foley carriers.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cateteres Urinários/efeitos adversos , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Registros , Método Simples-Cego
9.
Br J Pharmacol ; 172(2): 287-96, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24460711

RESUMO

UNLABELLED: Opioids, such as morphine, are the most clinically useful class of analgesic drugs for the treatment of acute and chronic pain. However, the use of opioids is greatly limited by the development of severe adverse side effects. Consequently, drug discovery efforts have been directed towards improving the therapeutic profile of opioid-based treatments. Opioid receptors are members of the family of GPCRs. As such, the recent GPCR paradigms of biased agonism and allosterism may provide novel avenues for more effective analgesics. Biased agonism (or functional selectivity) has been described for all the opioid receptor family members. Furthermore, the first allosteric modulators of opioid receptors have very recently been described. However, identification and quantification of biased agonism in a manner that is informative to medicinal chemists and drug discovery programmes still remains a challenge. In this review, we examine the progress, to date, towards identification and quantification of biased agonism and allosterism at the µ-opioid receptor in the context of its implications for the discovery of better and safer analgesics. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.


Assuntos
Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Animais , Descoberta de Drogas , Humanos , Ligantes , Dor/tratamento farmacológico , Dor/metabolismo
10.
Acta Biotheor ; 63(1): 71-81, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25084999

RESUMO

The extreme sexual size dimorphism in spiders has motivated studies for many years. In many species the male can be very small relative to the female. There are several hypotheses trying to explain this fact, most of them emphasizing the role of energy in determining spider size. The aim of this paper is to review the role of energy in sexual size dimorphism of spiders, even for those spiders that do not necessarily live in high foliage, using physical and allometric principles. Here we propose that the cost of transport or equivalently energy expenditure and the speed are traits under selection pressure in male spiders, favoring those of smaller size to reduce travel costs. The morphology of the spiders responds to these selective forces depending upon the lifestyle of the spiders. Climbing and bridging spiders must overcome the force of gravity. If bridging allows faster dispersal, small males would have a selective advantage by enjoying more mating opportunities. In wandering spiders with low population density and as a consequence few male-male interactions, high speed and low energy expenditure or cost of transport should be favored by natural selection. Pendulum mechanics show the advantages of long legs in spiders and their relationship with high speed, even in climbing and bridging spiders. Thus small size, compensated by long legs should be the expected morphology for a fast and mobile male spider.


Assuntos
Metabolismo Energético , Caracteres Sexuais , Aranhas , Animais , Feminino , Masculino , Aranhas/metabolismo
11.
Int Marit Health ; 64(1): 30-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23788163

RESUMO

BACKGROUND: The social security protection is one of the essential elements of decent work. The issue is complexand no previous epidemiological studies of the coverage among the seafarers have yet been performed. AIM: The aim was to overcome the gap of knowledge to promote the further discussion and plan the implementationof the social security for all the seafarers. MATERIALS AND METHODS: The seafarers completed a short questionnaire concerning their knowledge abouttheir social security status. RESULTS: The significant disparities in the social security coverage were pointed out among the nationalities.Especially it is worth mentioning that more than half of the respondents believe they are economicallyuncovered for disability from an injury on board and from a work-related disease. CONCLUSIONS: The results confirm the ILO (Convention No. 143) statements that the significant part of theseafarers comes from the poorer countries without the substantial social security systems. The solutionssuggested are to implement the minimum requirements as recommended by the ILO 2006 Convention, tosurvey the implementation and - in the long term - to struggle for a global social equality.


Assuntos
Navios , Previdência Social , Adulto , Coleta de Dados , Feminino , Saúde Global , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Previdência Social/organização & administração , Inquéritos e Questionários , Recursos Humanos , Adulto Jovem
12.
Arzneimittelforschung ; 62(10): 482-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22918855

RESUMO

A bioequivalence study of 2 zolmitriptan (CAS 139264-17-8) orodispersible tablet formulations was carried out in 26 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Plasma concentrations of zolmitriptan and its active metabolite (N-desmethyl-zolmitriptan) were obtained by LC/MS/MS method. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80-125%. According to the European Guideline 1 it may be therefore concluded that test formulation of zolmitriptan 5 mg orodispersible tablet is bioequivalent to the reference formulation.


Assuntos
Oxazolidinonas/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Triptaminas/farmacologia , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Bases de Dados Factuais , Método Duplo-Cego , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Oxazolidinonas/administração & dosagem , Oxazolidinonas/farmacocinética , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/farmacocinética , Comprimidos , Espectrometria de Massas em Tandem , Equivalência Terapêutica , Triptaminas/administração & dosagem , Triptaminas/farmacocinética , Adulto Jovem
13.
Arzneimittelforschung ; 62(2): 59-62, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22344549

RESUMO

This study was designed to compare the rate and extent of absorption of 2 oral formulations of ondansetron (CAS 99614-02-5) 8 mg orodispersible tablets in healthy volunteers. 22 subjects were administered ondansetron orodispersible tablets of test and reference formulation in a single-dose, 2-period, 2-sequence, fasting, open-label, crossover and randomised study. Plasma concentrations were determined by LC/MS/MS. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80-125%. According to the European Guideline [1] it may be therefore concluded that test formulation of ondansetron 8 mg orodispersible tablet is bioequivalent to the reference formulation.


Assuntos
Antieméticos/farmacocinética , Ondansetron/farmacocinética , Adolescente , Adulto , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Método Duplo-Cego , Feminino , Meia-Vida , Humanos , Masculino , Ondansetron/administração & dosagem , Ondansetron/efeitos adversos , Tamanho da Amostra , Espectrometria de Massas em Tandem , Equivalência Terapêutica , Adulto Jovem
14.
Br J Pharmacol ; 166(3): 898-911, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21883151

RESUMO

BACKGROUND AND PURPOSE: The chemokine receptor CXCR3 is a GPCR found predominantly on activated T cells. CXCR3 is activated by three endogenous peptides; CXCL9, CXCL10 and CXCL11. Recently, a small-molecule agonist, VUF10661, has been reported in the literature and synthesized in our laboratory. The aim of the present study was to provide a detailed pharmacological characterization of VUF10661 by comparing its effects with those of CXCL11. EXPERIMENTAL APPROACH: Agonistic properties of VUF10661 were assessed in a chemotaxis assay with murine L1.2 cells transiently transfected with cDNA encoding the human CXCR3 receptor and in binding studies, with [(125)I]-CXCL10 and [(125)I]-CXCL11, on membrane preparations from HEK293 cells stably expressing CXCR3. [(35)S]-GTPγS binding was used to determine its potency to induce CXCR3-mediated G protein activation and BRET-based assays to investigate its effects on intracellular cAMP levels and ß-arrestin recruitment. KEY RESULTS: VUF10661 acted as a partial agonist in CXCR3-mediated chemotaxis, bound to CXCR3 in an allosteric fashion in ligand binding assays and activated G(i) proteins with the same efficacy as CXCL11 in the [(35)S]-GTPγS binding and cAMP assay, while it recruited more ß-arrestin1 and ß-arrestin2 to CXCR3 receptors than the chemokine. CONCLUSIONS AND IMPLICATIONS: VUF10661, like CXCL11, activates both G protein-dependent and -independent signalling via the CXCR3 receptor, but probably exerts its effects from an allosteric binding site that is different from that for CXCL11. It could stabilize different receptor and/or ß-arrestin conformations leading to differences in functional output. Such ligand-biased signalling might offer interesting options for the therapeutic use of CXCR3 agonists.


Assuntos
Isoquinolinas/farmacologia , Receptores CXCR3/agonistas , Bibliotecas de Moléculas Pequenas/farmacologia , Regulação Alostérica , Animais , Técnicas de Cultura de Células , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/metabolismo , Quimiotaxia/efeitos dos fármacos , AMP Cíclico/metabolismo , DNA Complementar/genética , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Isoquinolinas/química , Ligantes , Camundongos , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/efeitos dos fármacos , Células Precursoras de Linfócitos B/metabolismo , Ligação Proteica , Ensaio Radioligante , Receptores CXCR3/antagonistas & inibidores , Receptores CXCR3/genética , Receptores de Superfície Celular/biossíntese , Bibliotecas de Moléculas Pequenas/química , Transfecção
15.
Br J Pharmacol ; 165(6): 1617-1643, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21699506

RESUMO

G protein-coupled chemokine receptors and their peptidergic ligands are interesting therapeutic targets due to their involvement in various immune-related diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, chronic obstructive pulmonary disease, HIV-1 infection and cancer. To tackle these diseases, a lot of effort has been focused on discovery and development of small-molecule chemokine receptor antagonists. This has been rewarded by the market approval of two novel chemokine receptor inhibitors, AMD3100 (CXCR4) and Maraviroc (CCR5) for stem cell mobilization and treatment of HIV-1 infection respectively. The recent GPCR crystal structures together with mutagenesis and pharmacological studies have aided in understanding how small-molecule ligands interact with chemokine receptors. Many of these ligands display behaviour deviating from simple competition and do not interact with the chemokine binding site, providing evidence for an allosteric mode of action. This review aims to give an overview of the evidence supporting modulation of this intriguing receptor family by a range of ligands, including small molecules, peptides and antibodies. Moreover, the computer-assisted modelling of chemokine receptor-ligand interactions is discussed in view of GPCR crystal structures. Finally, the implications of concepts such as functional selectivity and chemokine receptor dimerization are considered.


Assuntos
Receptores de Quimiocinas/metabolismo , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Quimiocinas/metabolismo , Desenho de Fármacos , Humanos , Receptores de Quimiocinas/agonistas , Receptores de Quimiocinas/antagonistas & inibidores
16.
J Insect Physiol ; 57(11): 1489-94, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21821038

RESUMO

The metabolic and water evaporation strategies in spiders may be part of a set of physiological adaptations to tolerate low or unpredictable food availability, buffering spiders against environmental fluctuations such as those of the high mountains of the central Andes. The aim of this study is to analyze experimentally the variations in metabolic rate and the rate of evaporative water with food and/or water restriction in a high mountain mygalomorph spider population (Paraphysa sp.). We found that the low metabolism of this spider was not affected by water restriction, but its metabolism was depressed after 3 weeks of food deprivation. The spider did not show seasonal metabolic changes but it presented seasonal changes in the rate of evaporative water loss at high temperatures. Females with egg sacs reduced their metabolic rate and evaporative water at high temperatures. These findings constitute a set of possible adaptations to a highly fluctuating Mediterranean environment, which is completely covered with snow for many months and then progresses rapidly to a very dry climate with high temperatures.


Assuntos
Metabolismo Basal , Privação de Alimentos , Aranhas/metabolismo , Privação de Água , Perda Insensível de Água , Altitude , Animais , Dióxido de Carbono/metabolismo , Chile , Feminino , Água/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-21496493

RESUMO

One of the hypotheses that attempt to explain physiological limitations of energy budgets is the symmorphosis hypothesis, which proposes that if matching structures to functional needs were combined with the strict economy of energy and materials, the result would be an optimal organ design for the specific function it serves. Evidence in favor of symmorphosis in adults is as abundant as evidence against it, but the plasticity of some morphological traits may be dependent on the ontogenetic stage at which acclimation acts. Thus, here we studied the adjustment of structure and function in lungs at different stages of development in the quail Coturnix coturnix japonica under two thermal regimes. Our main results show that i) resting metabolic rate, maximum thermogenic oxygen consumption and oxygen diffusion capacity did not exhibit developmental plasticity for two thermal environments; and ii) oxygen diffusion capacity fully adjusted to resting metabolic rate and maximum oxygen consumption during development. C. coturnix has a low safety factor close to 1 which is consistent with the symmorphosis hypothesis.


Assuntos
Coturnix/crescimento & desenvolvimento , Oxigênio/metabolismo , Animais , Coturnix/metabolismo , Metabolismo Energético
19.
J Insect Physiol ; 56(7): 731-5, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20064521

RESUMO

Small animals need efficient water conservation mechanisms for survival and reproduction, which is relevant for the spiders that have large book lungs with large respiratory surface. If lung evaporation is relevant to limit water loss, adjustments of the spiracle opening to metabolic demands should be expected. In this study, we measured the metabolic rate and total evaporative water loss mediated by the opening of the spiracles in the migalomorph spider Paraphysa parvula, a resident of fluctuating Mediterranean environments of the mountains of central Chile. We found that the metabolism of P. parvula was similar to other Theraphosidae and low compared to other arthropods. Carbon dioxide production and evaporative water loss increased with temperature, particularly at 40 degrees C. The total evaporative water loss at 40 degrees C increased dramatically to about 10 times that found with the lower temperatures. Thus, 40 degrees C will be the limit temperature for this species after which evaporative water loss starts to become damaging, so it has to avoid it. The exposition to hypercapnic environments had as a consequence an increase in evaporative water loss and the involvement of the book lungs in this loss was about 60%. The possibility of losing water could condition this species to seek temperate and oxygenated shelters under rocks.


Assuntos
Aranhas/metabolismo , Água/metabolismo , Animais , Dióxido de Carbono/metabolismo , Chile , Pulmão/metabolismo
20.
Int. j. morphol ; 27(4): 985-988, dic. 2009. ilus
Artigo em Inglês | LILACS | ID: lil-582039

RESUMO

We examined the status of the first metacarpal bone whose shape, fetal and post-natal development correspond to those of the thumb proximal phalanx. Galen already described this, circa 170 CE. Our radiographic data confirm that the pre-axial (radial or anterior) side of the hand matures, later than the post-axial (ulnar or posterior) side, both, pre- and post-natally. A new perspective on thumb primate and human ontogeny is discussed and comparative observations on the Evolutionary Development (EvoDevo) of the thumb and the first toe are proposed along with a nomenclature honoring Galen's original roposition.


Se analiza el estado del primer metacarpiano cuya forma y desarrollo embrionario, fetal y postnatal corresponde a los de la primera falange del pulgar. Galeno notó que éste era la primera falange del pulgar cerca de 170 DC. Esto no es un simple cambio de nomenclatura, ya que da una nueva luz a los problemas evolutivos de ontogenia (EvoDevo). Nuestros datos radiográficos confirman que el lado radial (anterior o pre-axial) de la mano madura, pre y post-natalmente, mas tardíamente que el lado cubital (posterior o post-axial). Se discuten nuevas perspectivas sobre la ontogenia y filogenia humana y de primates, y se proponen estudios comparativos del desarrollo del pulgar y del ortejo mayor.


Assuntos
Humanos , Masculino , Adolescente , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Falanges dos Dedos da Mão/crescimento & desenvolvimento , Ossos Metacarpais/crescimento & desenvolvimento , Polegar/crescimento & desenvolvimento , Desenvolvimento Ósseo , Biologia do Desenvolvimento , Falanges dos Dedos da Mão , Ossos Metacarpais , Polegar
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