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1.
Sci Total Environ ; 652: 320-329, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30366333

RESUMO

The AQUACROSS project was an unprecedented effort to unify policy concepts, knowledge, and management of freshwater, coastal, and marine ecosystems to support the cost-effective achievement of the targets set by the EU Biodiversity Strategy to 2020. AQUACROSS aimed to support EU efforts to enhance the resilience and stop the loss of biodiversity of aquatic ecosystems as well as to ensure the ongoing and future provision of aquatic ecosystem services. The project focused on advancing the knowledge base and application of Ecosystem-Based Management. Through elaboration of eight diverse case studies in freshwater and marine and estuarine aquatic ecosystem across Europe covering a range of environmental management problems including, eutrophication, sustainable fisheries as well as invasive alien species AQUACROSS demonstrated the application of a common framework to establish cost-effective measures and integrated Ecosystem-Based Management practices. AQUACROSS analysed the EU policy framework (i.e. goals, concepts, time frames) for aquatic ecosystems and built on knowledge stemming from different sources (i.e. WISE, BISE, Member State reporting within different policy processes, modelling) to develop innovative management tools, concepts, and business models (i.e. indicators, maps, ecosystem assessments, participatory approaches, mechanisms for promoting the delivery of ecosystem services) for aquatic ecosystems at various scales of space and time and relevant to different ecosystem types.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais/métodos , Ecossistema , Monitoramento Ambiental , Política Ambiental , Europa (Continente) , Eutrofização , Pesqueiros , Água Doce
2.
Pol J Vet Sci ; 20(4): 769-778, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29611660

RESUMO

Aryl hybrocardon receptor (AhR) activation plays a key role in the pathomechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced defective spatial structure of teeth caused by disordered collagen synthesis. The aim of this study was to identify the influence of dioxins present in female Buffalo rats on the dental structure of their offspring's in the neonatal period and the potential of α-tocopherol and acetylsalicylic acid in curbing post-dioxin hard tissue defects. Research material consisted of molar teeth (n=40) of rat pups which had been given a single dose of TCDD and were then treated with tocopherol or acetylsalicylic acid for 3 weeks. In the offspring of rat dams exposed to TCDD, ameloblasts and odontoblasts were less developed in comparison with the control group and less dynamic angiogenesis in the area of dental papilla was observed. In the pups of TCDD-exposed mothers, a smaller number of AhR was found in amelogenic and odontoblastic cells, whereas in the pups of mothers exposed to TCDD followed by tocopherol and acetylsalicylic acid treatment, the expression of AhR in ameloblasts and odontoblasts increased. We conclude that tocopherol and acetylsalicylic acid treatment exerts a protective effect on the TCDD-induced structural defects of tooth tissue.


Assuntos
Aspirina/farmacologia , Dibenzodioxinas Policloradas/toxicidade , Tocoferóis/farmacologia , Anormalidades Dentárias/induzido quimicamente , Dente/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Poluentes Ambientais , Feminino , Imuno-Histoquímica , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos
3.
Pol J Vet Sci ; 19(1): 109-18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27096794

RESUMO

The implementation of new methods of osteoporotic therapy requires tests on animal model. The use of sheep as model has numerous advantages over other animals. The aim of this study was to describe the change in parameters in sheep with osteoporosis induced using steroids and ovariorectomy methods as opposed to the parameters in healthy sheep. The study was performed on female "merinos" breed sheep divided into the three groups: negative control (NC)--healthy animals, positive control (PC)--ovariorectomized animals and steroid control group (SC)--in which methylprednisolone was administered. This paper presents histological and ultrastructural examination with mechanical comparative tests for force/strength values as well as indentation tests of joint cartilage. The obtained results confirm the loss of bone mass associated with mineral composition content in bones, which has an influence on bone strength.


Assuntos
Metilprednisolona/toxicidade , Osteoporose/veterinária , Ovariectomia/veterinária , Doenças dos Ovinos/etiologia , Animais , Fenômenos Biomecânicos , Densidade Óssea , Feminino , Glucocorticoides/toxicidade , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Ovinos
4.
Pol J Vet Sci ; 19(1): 213-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27096806

RESUMO

This study presents and evaluates side-to-side nerve repair techniques for their ability to induce collateral nerve sprouting. The coaptation of the ventral branches of spinal nerves C5 and C6 to C7 through an incision epineurium was used to repair the nerve. The number of myelinated fiber axons and G-ratio was evaluated. Preliminary results indicate the possibility of using side to side coaptation in brachial plexus nerve surgery.


Assuntos
Procedimentos Neurocirúrgicos/veterinária , Nervos Periféricos/cirurgia , Animais , Membro Anterior/inervação , Coelhos
5.
Pol J Vet Sci ; 18(2): 367-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26172187

RESUMO

The gait is a form of human and animal locomotion on land by using limbs. The study assessed functional recovery after end to side and side to side neurorrhaphy the ventral branches of the C5 and C6 spinal nerves to the C7 spinal nerve on the rabbit brachial plexus. Gait statistical analysis showed significant differences between the control group versus the end-to-side and side to side neurorrhaphy groups, in opposite to the comparison between the two experimentals groups. Gait analysis results corresponded with the histomorphometric results. The results indicate the potential use of gait analysis for the assessment of the recovery of nerve function.


Assuntos
Plexo Braquial/cirurgia , Marcha/fisiologia , Coelhos , Animais
6.
Pol J Vet Sci ; 17(2): 339-45, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24988861

RESUMO

The aim of our study was to analyze the anatomy and surgical approach of the rabbit brachial plexus. The research included 18 rabbits. The rabbit seems to be a good experimental model for spinal nerves injury, especially for the C5 and C6 segments. The anatomical structure of the rabbit's brachial plexus is similar to the human brachial plexus. The structure of the rabbit C5 and C6 segments is analogous to the human structure. The spinal nerves of the C5 and C6 segments in the rabbit are wide and long enough for microsurgical procedures.


Assuntos
Plexo Braquial/anatomia & histologia , Coelhos/anatomia & histologia , Animais , Feminino
7.
Clin Toxicol (Phila) ; 52(6): 629-34, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24844578

RESUMO

CONTEXT: Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. OBJECTIVES: To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. METHODS: A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. RESULTS: We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4-50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8-29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3-19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5-17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4-14.0%). In adolescents (15-19y/o) 23.9% (95% CI: 17.6-31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3-9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8-35.2%) and 10.9% (95% CI: 7.1-16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. CONCLUSIONS: Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults. "Part of this work is already published as a conference abstract for the XXXIV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 27-30 May 2014, Brussels, Belgium." Abstract 8, Clin Toxicol 2014;52(4):298.


Assuntos
Overdose de Drogas/complicações , Convulsões/induzido quimicamente , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/efeitos adversos , Criança , Pré-Escolar , Citalopram/efeitos adversos , Cicloexanóis/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Ácido Mefenâmico/efeitos adversos , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Estudos Retrospectivos , Suíça/epidemiologia , Trimipramina/efeitos adversos , Cloridrato de Venlafaxina , Adulto Jovem
8.
Water Res ; 47(17): 6762-79, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24112629

RESUMO

Accurate predictions of future conditions of sewer systems are needed for efficient rehabilitation planning. For this purpose, a range of sewer deterioration models has been proposed which can be improved by calibration with observed sewer condition data. However, if datasets lack historical records, calibration requires a combination of deterioration and sewer rehabilitation models, as the current state of the sewer network reflects the combined effect of both processes. Otherwise, physical sewer lifespans are overestimated as pipes in poor condition that were rehabilitated are no longer represented in the dataset. We therefore propose the combination of a sewer deterioration model with a simple rehabilitation model which can be calibrated with datasets lacking historical information. We use Bayesian inference for parameter estimation due to the limited information content of the data and limited identifiability of the model parameters. A sensitivity analysis gives an insight into the model's robustness against the uncertainty of the prior. The analysis reveals that the model results are principally sensitive to the means of the priors of specific model parameters, which should therefore be elicited with care. The importance sampling technique applied for the sensitivity analysis permitted efficient implementation for regional sensitivity analysis with reasonable computational outlay. Application of the combined model with both simulated and real data shows that it effectively compensates for the bias induced by a lack of historical data. Thus, the novel approach makes it possible to calibrate sewer pipe deterioration models even when historical condition records are lacking. Since at least some prior knowledge of the model parameters is available, the strength of Bayesian inference is particularly evident in the case of small datasets.


Assuntos
Modelos Teóricos , Esgotos , Calibragem , Funções Verossimilhança , Cadeias de Markov , Método de Monte Carlo , Engenharia Sanitária
10.
Environ Sci Technol ; 46(1): 112-8, 2012 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-22208812

RESUMO

Switzerland provides an example of successful management of water infrastructure and water resources that was accomplished largely without integration across sectors. Limitations in this approach have become apparent; decisions that were formerly based only on technical and economic feasibility must now incorporate broader objectives such as ecological impact. In addition, current and emerging challenges relate to increasingly complex problems that are likely to demand more integrated approaches. If such integration is to be of benefit, it must be possible to redirect resources across sectors, and the synergies derived from integration must outweigh the additional cost of increased complexity.


Assuntos
Conservação dos Recursos Naturais/métodos , Rios , Água , Conservação dos Recursos Naturais/legislação & jurisprudência , Eutrofização , Humanos , Suíça
11.
Euro Surveill ; 14(7)2009 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-19232227

RESUMO

In the last quarter of 2008, an outbreak of mumps occurred in Luxembourg affecting initially 10 young adults at a military centre. Following a mass vaccination campaign, no further clinical cases were observed. 90% of 136 vaccine recipients were IgG positive one month after vaccination compared to 54% before vaccination. Until 31 December 2008, 19 mumps cases were also reported from the community. The outbreak strain belonged to genogroup G.


Assuntos
Controle de Doenças Transmissíveis/métodos , Militares , Caxumba/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Programas de Imunização , Luxemburgo/epidemiologia , Masculino , Caxumba/diagnóstico , Caxumba/prevenção & controle , Vírus da Caxumba/isolamento & purificação , Avaliação de Programas e Projetos de Saúde , Estudos Soroepidemiológicos , Adulto Jovem
12.
Euro Surveill ; 13(31)2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18761903

RESUMO

Outbreaks of Clostridium difficile infections (CDI) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America and Europe. This emerging strain is referred to as PCR ribotype 027 (Type 027). Since 2005, individual countries have developed surveillance studies about the spread of type 027.C. difficile Type 027 has been reported in 16 European countries. It has been responsible for outbreaks in Belgium, Germany, Finland, France, Ireland, Luxembourg, The Netherlands, Switzerland and the United Kingdom (England, Wales, Northern Ireland and Scotland). It has also been detected in Austria, Denmark, Sweden, Norway, Hungary, Poland and Spain. Three countries experienced imported patients with CDI due to Type 027 who acquired the infection abroad.The antimicrobial resistance pattern is changing, and outbreaks due to clindamycin-resistant ermB positive Type 027 strains have occurred in three European countries. Ongoing epidemiological surveillance of cases of CDI, with periodic characterisation of the strains involved, is required to detect clustering of cases in time and space and to monitor the emergence of new, highly virulent clones.


Assuntos
Clostridioides difficile/genética , Clostridioides difficile/patogenicidade , Surtos de Doenças , Enterocolite Pseudomembranosa/epidemiologia , Reação em Cadeia da Polimerase , Ribotipagem , Europa (Continente)/epidemiologia , União Europeia , Humanos , Vigilância da População
13.
Euro Surveill ; 12(6): E1-2, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17991399

RESUMO

Recent outbreaks of Clostridium difficile-associated diarrhoea (CDAD) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America, Japan and Europe. Definitions have been proposed by the European Centre of Disease Prevention and Control (ECDC) to identify severe cases of CDAD and to differentiate community-acquired cases from nosocomial CDAD (http://www.ecdc.europa.eu/documents/pdf/Cl_dif_v2.pdf). CDAD is mainly known as a healthcare-associated disease, but it is also increasingly recognised as a community-associated disease. The emerging strain is referred to as North American pulsed-field type 1 (NAP1) and PCR ribotype 027. Since 2005, individual countries have developed surveillance studies to monitor the spread of this strain. C. difficile type 027 has caused outbreaks in England and Wales, Ireland, the Netherlands, Belgium, Luxembourg, and France, and has also been detected in Austria, Scotland, Switzerland, Poland and Denmark. Preliminary data indicated that type 027 was already present in historical isolates collected in Sweden between 1997 and 2001.


Assuntos
Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Surtos de Doenças/estatística & dados numéricos , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/microbiologia , Ribotipagem/estatística & dados numéricos , Medição de Risco/métodos , Clostridioides difficile/classificação , Europa (Continente)/epidemiologia , Humanos , Incidência , Reação em Cadeia da Polimerase , Vigilância da População , Fatores de Risco , Especificidade da Espécie
14.
AJNR Am J Neuroradiol ; 27(10): 2199-201, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17110693

RESUMO

Giant cell tumor (GCT) of the sphenoid bone is a relatively rare entity and metachronous multicentric GCT of the sphenoid is even rarer; we are aware of only 3 previous cases in the literature. We describe here a tumor of the sphenoid bone that was identified 15 years after multiple resections of a GCT of the left inferior pubic ramus. Correlation is made between the histopathologic findings, MR imaging of the brain, CT of the head, and fusion positron-emission tomography (PET)/CT scan performed with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). This report is the first to describe the appearance of a GCT of the sphenoid bone on a fusion PET/CT examination. High metabolic activity in the base of the skull adjacent to the middle cranial fossa was demonstrated in a fashion similar to that of the known pelvic lesion. This case also demonstrates that the increased metabolic activity seen in a GCT of the sphenoid bone may be partially obscured by the adjacent physiologic high metabolic activity of the brain.


Assuntos
Tumor de Células Gigantes do Osso/diagnóstico , Imageamento por Ressonância Magnética , Segunda Neoplasia Primária/diagnóstico , Tomografia por Emissão de Pósitrons , Neoplasias Cranianas/diagnóstico , Osso Esfenoide , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos
15.
Water Sci Technol ; 53(1): 267-75, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16532757

RESUMO

A simple interface between simulation programs and systems analytical software is proposed. This interface is designed to facilitate linkage of environmental simulation programs with systems analytical software and thus can contribute to remedying the deficiency in applying systems analytical techniques to environmental modelling studies. The proposed concept, consisting of a text file interface combined with a batch mode simulation program call, is independent of model structure, operating system and programming language. It is open for implementation by academic and commercial simulation and systems analytical software developers and is very simple to implement. Its practicability is demonstrated by implementations for three environmental simulation packages (AQUASIM, SWAT and LEACHM) and two systems analytical program packages (UNCSIM, SUFI). The properties listed above and the demonstration of the ease of implementation of the approach are prerequisites for the stimulation of a widespread implementation of the proposed interface that would be beneficial for the dissemination of systems analytical techniques in the environmental and engineering sciences. Furthermore, such a development could stimulate the transfer of systems analytical techniques between different fields of application.


Assuntos
Modelos Teóricos , Software , Eliminação de Resíduos Líquidos , Meio Ambiente
16.
J Anim Breed Genet ; 122 Suppl 1: 22-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16130453

RESUMO

Separation of X- and Y-bearing sperm cells, together with artificial insemination using sex-specific semen, makes it possible to pre-determine the sex of calves. This has the potential to considerably improve cattle breeding, genetic resource management and particularly the efficiency of dairy and meat production. However, the broad use of sexed semen will depend on availability, price, fertilizability and in particular the actual sorting purity of sperm doses. To validate the accuracy of sperm sexing in Bos taurus, we have developed a simple, fast and reliable dual colour fluorescence in situ hybridization (FISH) test, where Y-bearing spermatozoa are identified by a DNA fragment hybridizing to a large pericentromeric repetitive DNA block on the bovine Y chromosome (locus DYZI, Yp13-q12). To avoid an underestimation of Y signals, we used a second DNA probe identifying a large subcentromeric block of complex repetitive DNA on the bovine autosome 6 (locus D6Z1, 6q12-15) as a positive control. Bovine sperm were fixed with methanol:acetic acid and denatured by simply immersing in 3 M NaOH, yielding consistent hybridization results and good preservation of sperm morphology. The FISH protocol was evaluated on unsorted sperm as well as on sperm samples sexed using the Beltsville technology, which separates X- and Y-bearing spermatozoa by staining with Hoechst 33342 and flow sorting according to their DNA content (Johnson et al. 1987).


Assuntos
Cruzamento/métodos , Bovinos/genética , Análise para Determinação do Sexo/métodos , Espermatozoides/química , Cromossomo Y/genética , Animais , Primers do DNA , Hibridização in Situ Fluorescente/métodos , Hibridização in Situ Fluorescente/veterinária , Masculino , Reprodutibilidade dos Testes
17.
Theriogenology ; 64(7): 1647-55, 2005 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15904953

RESUMO

The present study was performed to test fertility after low dose insemination with sexed and non-sexed sperm in dairy cattle under field conditions in Switzerland. Spermatozoa were stained with Hoechst 33342 and sorted by flow cytometry. A total of 132 heifers and cows were inseminated with 2 x 10(6) X-bearing, frozen-thawed sperm (A) and 91 animals were inseminated with the same dose using non-sorted, frozen-thawed sperm (B). Pregnancy examination by ultrasound was performed twice, 30-40 days (PE1) and 70-90 days (PE2) after insemination. The pregnancy rates after PE1 were 33.3% (9/27) and 59.3% (16/27) in heifers (P=0.05) and 27.6% (29/105) and 28.1% (18/64) in cows (P>0.05) for groups A and B, respectively. Embryonic losses between PE1 and PE2 in heifers were 11.1% (1/9) and 0% (0/16) and in cows 17.2% (5/29) and 5.6% (1/18), the differences between groups A and B not being significant (P>0.05). Calving rates in heifers were 29.6% (8/27) and 57.8% (15/26), whereas in cows 22.1% (23/104) and 23.4% (16/63) gave birth to calves (for both groups P>0.05). The sex ratio was different (P<0.05) between A (85.3%) and B (58.6%). From our results it can be concluded that conception rates of sorted and non-sorted semen are similar using an insemination dose of 2 x 10(6). Fertility may be increased by improving sexing technology and animal management.


Assuntos
Bovinos/fisiologia , Separação Celular/veterinária , Fertilidade , Inseminação Artificial/veterinária , Análise para Determinação do Sexo/veterinária , Espermatozoides/fisiologia , Animais , Criopreservação/veterinária , Feminino , Citometria de Fluxo , Inseminação Artificial/métodos , Masculino , Gravidez , Preservação do Sêmen/veterinária
18.
Transplant Proc ; 36(4): 1007-8, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15194350

RESUMO

Small-for-size livers are associated with graft dysfunction, probably due to portal hyperperfusion. Modulation of the recipient portal inflow is a new option in these cases. This article sought to analyze the effect of portocaval shunt in small-for-size liver grafts in pigs. Twelve liver transplants were performed in white pigs. The donors' mean weight was 10 kg and the recipient's mean weight was 34 kg. In all cases a standard technique was utilized. A portocaval shunt was added on the back-table in six cases. One hour after the procedure, the livers were sent for histologic examination. In all six cases without a portocaval shunt, the livers showed hemorrhagic necrosis, which was not observed in any of the six livers with a portocaval shunt. In small-for-size liver grafts in pigs, a portocaval shunt prevents hemorrhagic necrosis.


Assuntos
Transplante de Fígado/métodos , Veia Porta/cirurgia , Derivação Portossistêmica Cirúrgica/métodos , Veia Cava Inferior/cirurgia , Animais , Peso Corporal , Feminino , Modelos Animais , Suínos
19.
Biophys Chem ; 101-102: 239-47, 2002 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-12488004

RESUMO

Removal of the N-terminal formyl group from newly synthesized proteins by the enzyme peptide deformylase (PDF) is essential for normal growth of bacteria but not higher organisms. Recently, PDF has been explored as a target for novel antibiotics. Screening a collection of natural products for antimicrobial activity identified actinonin and two matlystatin analogs as potent PDF inhibitors. A number of synthetic analogs of these natural products were prepared and their inhibitory potency determined. Previous work has shown that PDF is an iron metalloproteinase also containing a catalytic glutamic acid residue. Ligation of the ferrous cation is an essential feature of potent inhibitors. The structures of actinonin, a matlystatin analog and a synthetic inhibitor complexed with PDF were determined by crystallography. A quantum mechanics/molecular mechanics (QM/MM) method was used to reproduce the geometry of known complexes, to predict the protonation state in the active site and to predict the geometry of additional complexes. The requirement for protonation of the active site glutamate anion is an important factor in understanding the potency of inhibitors with acidic iron-ligating groups such as hydroxamate and carboxylate. Even though potent inhibitors of PDF have been discovered, their bacteriostatic mechanism of action and the rapid development of resistance in vitro may limit their potential as antibacterial drugs.


Assuntos
Amidoidrolases , Aminopeptidases/antagonistas & inibidores , Inibidores Enzimáticos/metabolismo , Metais/metabolismo , Inibidores Enzimáticos/química , Ligantes , Metais/química , Modelos Moleculares
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