Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
Occup Med (Lond) ; 73(7): 391-397, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37682842

RESUMO

BACKGROUND: Hearing loss leads to increased irritability and disengagement in social activities and conversations, which may impact quality of life. Dental professionals are at risk of developing hearing loss through daily exposure to noise from a wide range of equipment that produces significantly high decibels and noise frequencies. AIMS: The aim of this systematic review was to investigate the risk of hearing loss in dental professionals, including dentists, dental specialists, dental hygienists and dental assistants. METHODS: This review was conducted following the Cochrane Handbook for Systematic Reviews. PubMed, Scopus, Embase, Cochrane, Science Direct, Google Scholar and ProQuest were searched up to March 2023. Seventeen of 416 studies met the inclusion criteria. Quality assessment was performed according to the Newcastle-Ottawa Scale for cohort and case-control studies, and a modified version of this tool for cross-sectional studies. RESULTS: The majority of included studies (82%) found a positive association with hearing loss for dentists and dental specialists, with years of clinical experience identified as a prominent risk factor. Dental hygienists and dental assistants were less commonly reported in the literature. Difference between the left and right ears was found in 71% of studies, with the left ear more affected in both dentists and dental assistants due to proximity to the noise-inducing equipment. CONCLUSIONS: Dental professionals are at risk of hearing loss in their workplace, especially linked to years of clinical experience, which highlights the need for prevention and appropriate ear-protective devices.

2.
AAPS PharmSciTech ; 21(7): 278, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033939

RESUMO

People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.


Assuntos
Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Lidocaína/administração & dosagem , Miconazol/administração & dosagem , Nanopartículas/química , Polímeros/química , Antifúngicos/administração & dosagem , Antifúngicos/química , Varredura Diferencial de Calorimetria , Quitosana , Humanos , Lidocaína/química , Miconazol/química , Nanopartículas/administração & dosagem , Difração de Raios X
3.
AAPS PharmSciTech ; 19(8): 3712-3722, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30238304

RESUMO

Oropharyngeal candidiasis is a recurrent oral infection caused by Candida species. Gel formulation containing miconazole nitrate is the most common approach for treating oral candidiasis. However, traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the necessity to administrate various doses per day. Thus, the aim of this work was to formulate composited microparticulated systems based on combinations of mucoadhesive cationic, anionic, and nonionic polymers that could protect and modify the drug release rate and therefore avoid a fast dilution of the drug by saliva. Microparticulated systems were prepared by the spray drying method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The morphology of the systems was investigated by scanning electron microscopy; drug crystallinity was studied by X-ray, while interactions between polymers were analyzed by infrared spectroscopy. Drug release and halo zone test were employed to analyze the release and activity of the systems loaded with miconazole against Candida albicans cultures. The most appropriate microparticulated system was the one based on chitosan and gelatin which showed homogeneous morphology (mean size of 1.7 ± 0.5 µm), a protective effect of the drug, and better antifungal effect against Candida culture than miconazole nitrate and the other assayed systems. Taking into account these results, this approach should be seriously considered for further evaluation of its safety and in vivo efficacy to be considered as an alternative therapeutic system for the treatment of oral candidiasis.


Assuntos
Antifúngicos/química , Miconazol/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Quitosana/química , Composição de Medicamentos , Miconazol/farmacologia , Polímeros/química
4.
AAPS PharmSciTech ; 18(4): 936-946, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28108973

RESUMO

In this work, chitosan films were prepared by a casting/solvent evaporation methodology using pectin or hydroxypropylmethyl cellulose to form polymeric matrices. Miconazole nitrate, as a model drug, was loaded into such formulations. These polymeric films were characterized in terms of mechanical properties, adhesiveness, and swelling as well as drug release. Besides, the morphology of raw materials and films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity studied by differential scanning calorimetry and X-ray diffraction. In addition, antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. Chitosan:hydroxypropylmethyl cellulose films were found to be the most appropriate formulations in terms of folding endurance, mechanical properties, and adhesiveness. Also, an improvement in the dissolution rate of miconazole nitrate from the films up to 90% compared to the non-loaded drug was observed. The in vitro antifungal activity showed a significant activity of the model drug when it is loaded into chitosan films. These findings suggest that chitosan-based films are a promising approach to deliver miconazole nitrate for the treatment of candidiasis.


Assuntos
Candidíase Bucal/tratamento farmacológico , Quitosana , Sistemas de Liberação de Medicamentos , Derivados da Hipromelose/farmacologia , Miconazol , Adesividade , Administração Bucal , Antidiarreicos/química , Antidiarreicos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Quitosana/química , Quitosana/farmacologia , Composição de Medicamentos , Humanos , Miconazol/química , Miconazol/farmacologia , Microscopia Eletrônica de Varredura/métodos , Pectinas/química , Pectinas/farmacologia , Polímeros/farmacologia , Difração de Raios X/métodos
5.
Am J Infect Control ; 48(11): 1305-1310, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32442654

RESUMO

BACKGROUND: The objective is to know the evolution of the Degree of Compliance with Recommendations (DCR) on hand hygiene (HH) and its associated factors in the pediatric care areas (PCAs) of a tertiary hospital. METHODS: Observational, cross-sectional study, repeated over time, with direct observation of the DCR on HH during the daily activity of health care workers. Over 13 years, 9226 HH opportunities were observed. Associations between DCR, PCA and other variables (eg, age, sex, and professional position) were examined using χ² and adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: DCR on HH in 9 PCAs was 64.3% (95% CI, 63.3-65.3), and in the group of non-pediatric areas it was 49.6% (95% CI, 49.1-50.1). The areas with the highest degree of compliance were Oncology 72.8% (95% CI, 69.2-76.4), Neonatology 73.2% (95% CI, 71.3-75.1), and Neonatal intensive care unit 70.0% (95% CI, 67.5-72.6). These were the areas with the strongest association with HH compliance, with aOR:2.8 (95% CI, 2.2-3.6); aOR, 3.0 (95% CI, 2.6-3.6) aOR:2.6 (95% CI, 2.1-3.1), respectively. Other associated factors were the indications "after an activity," aOR, 1.6 (95% CI, 1.5-1.8) and the availability of pocket-size alcohol-based solution, aOR, 2.1(95% CI, 1.9-2.3). CONCLUSIONS: The DCR on HH in PCAs is higher than in other areas, although there is still margin for improvement. We have identified modifiable factors that have an independent association with HH compliance in PCAs. Focusing on modifiable factors will increase compliance with HH with the ultimate goal of reducing healthcare associated infections.


Assuntos
Infecção Hospitalar , Higiene das Mãos , Criança , Estudos Transversais , Fidelidade a Diretrizes , Humanos , Recém-Nascido , Controle de Infecções , Centros de Atenção Terciária
6.
Tuberculosis (Edinb) ; 117: 56-61, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31378269

RESUMO

Diagnostic tests based on cell-mediated immunity are used in programs for the control and eradication of bovine tuberculosis (bTB), which is mainly caused by Mycobacterium bovis. Additional serological assays could be performed as an ancillary method to detect an infected animal that fails to produce an immune response against the intradermal reaction (IDR), the official bTB test. In this study, we evaluated the effectiveness of an enzyme-linked immunosorbent assay (ELISA) that uses bovine PPD as a capture antigen as a complement to the IDR in herds with confirmed cases of bTB. The study was conducted in two stages. First, a panel of 200 serum samples was analyzed by ELISA. The sensitivity and specificity obtained were 60% and 99%, respectively. The subsequent stage consisted of evaluating 7,494 bovines from 14 selected dairy farms. The number of animals yielding a IDR negative/ELISA positive result were 200. A necropsy analysis of 33 of these IDR negative/ELISA positive animals revealed that 30 (91%) presented granulomatous lesions and positive M. bovis isolation. This finding confirmed bTB in most cases. Altogether, the results obtained in the present study suggest that the combined use of IDR and ELISA is an effective strategy to improve the control of bTB in endemic herds.


Assuntos
Ensaio de Imunoadsorção Enzimática/veterinária , Teste Tuberculínico/veterinária , Tuberculose Bovina/diagnóstico , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática/métodos , Reações Falso-Negativas , Mycobacterium bovis/imunologia , Sensibilidade e Especificidade , Tuberculina/imunologia , Teste Tuberculínico/métodos , Tuberculose Bovina/patologia
7.
Int J Pharm ; 548(1): 431-442, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30008423

RESUMO

Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.


Assuntos
Antifúngicos/administração & dosagem , Carragenina/administração & dosagem , Química Farmacêutica/métodos , Quitosana/administração & dosagem , Miconazol/administração & dosagem , Adesividade , Administração Bucal , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Carragenina/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Miconazol/química , Resistência à Tração
8.
Mater Sci Eng C Mater Biol Appl ; 79: 140-150, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28629000

RESUMO

Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva. Polymeric films loaded with miconazole nitrate were prepared by a casting/solvent evaporation methodology using chitosan, carbopol, gelatin, gum arabic, and alginate to form the polymeric matrices. The morphology of films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity by differential thermal analysis and X-ray diffraction. Films were characterized in terms of thickness, folding endurance, tensile properties, swelling, adhesiveness, and drug release. Finally, the antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. The more appropriate formulations were those based on chitosan-gelatin and chitosan-carbopol which showed good mechanical properties and adhesiveness, a relative low swelling index, improved drug release, and showed better in vitro activity against Candida cultures than miconazole nitrate raw material. Thus, it will be possible to produce a new pharmaceutical form based on polymeric films containing chitosan and miconazole nitrate, which could be loaded with low drug concentration producing the same therapeutic effect against Candida cultures.


Assuntos
Antifúngicos/química , Adesividade , Química Farmacêutica , Miconazol , Polímeros , Difração de Raios X
9.
J Biotechnol ; 186: 162-8, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25034430

RESUMO

The current validated endotoxin detection methods, in spite of being highly sensitive, present several drawbacks in terms of reproducibility, handling and cost. Therefore novel approaches are being carried out in the scientific community to overcome these difficulties. Remarkable efforts are focused on the development of endotoxin-specific biosensors. The key feature of these solutions relies on the proper definition of the capture protocol, especially of the bio-receptor or ligand. The aim of the presented work is the screening and selection of a synthetic peptide specifically designed for LPS detection, as well as the optimization of a procedure for its immobilization onto gold substrates for further application to biosensors.


Assuntos
Técnicas Biossensoriais/métodos , Proteínas Imobilizadas/química , Lipopolissacarídeos/análise , Peptídeos/química , Bactérias , Ensaio de Imunoadsorção Enzimática , Concentração de Íons de Hidrogênio , Proteínas Imobilizadas/metabolismo , Lipopolissacarídeos/química , Peptídeos/metabolismo , Técnicas de Microbalança de Cristal de Quartzo
10.
Innate Immun ; 16(1): 39-47, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19567486

RESUMO

The structural prerequisites for lipopolysaccharide (LPS) and its partial structures for the activation of the Limulus clotting cascade (Limulus amebocyte lysate [LAL] test) are described and compared with the corresponding requirements for the activation of human immune cells such as mononuclear cells. A necessary, but not sufficient, structural motif for this is the presence of the 4(')-phosphate-diglucosamine backbone recognition structure ('epitope') in lipid A. High activity is only expressed by assemblies of endotoxins, but this is largely independent of the type of supramolecular aggregate structure. A particular conformation of the epitope within the lipid A assembly must be present, which is influenced by addition of further saccharide units to the lipid A moiety, but also reacts slightly to the acylation pattern. In contrast, the cytokine production of human immune cells induced by LPS sensitively depends on the type of its aggregate structure. In the case of a hexa-acylated bisphosphorylated lipid A structure, high activity is only observed with cubic inverted aggregates. Furthermore, addition of antimicrobial agents (such as polymyxin B) leads to a nearly complete inhibition of cytokine production, whereas the reduction in the Limulus assay is much lower. These data are important since a reliable determination of endotoxin concentrations, in particular with respect to its ability to elicit severe infections, is of high interest.


Assuntos
Infecções Bacterianas/diagnóstico , Glucosamina/metabolismo , Leucócitos Mononucleares/metabolismo , Teste do Limulus/métodos , Lipídeo A/metabolismo , Animais , Infecções Bacterianas/sangue , Infecções Bacterianas/imunologia , Células Cultivadas , Citocinas/metabolismo , Endotoxinas/sangue , Endotoxinas/química , Glucosamina/análogos & derivados , Glucosamina/química , Caranguejos Ferradura , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Lipídeo A/análogos & derivados , Lipídeo A/química , Ativação Linfocitária , Valor Preditivo dos Testes , Multimerização Proteica , Projetos de Pesquisa
11.
J Bacteriol ; 175(16): 5273-5, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8349567

RESUMO

The patterns of susceptibility to hydrophobic and hydrophilic drugs and the uptake of the fluorescent probe N-phenyl-naphthylamine in Brucella spp., Haemophilus influenzae, Escherichia coli, and deep rough Salmonella minnesota mutants were compared. The results show that the outer membranes of smooth and naturally rough Brucella spp. do not represent barriers to hydrophobic permeants and that this absence of a barrier relates at least in part to the properties of Brucella lipopolysaccharide.


Assuntos
1-Naftilamina/análogos & derivados , Brucella/fisiologia , Permeabilidade da Membrana Celular , Membrana Celular/fisiologia , 1-Naftilamina/metabolismo , Escherichia coli/fisiologia , Haemophilus influenzae/fisiologia , Lipopolissacarídeos/metabolismo , Salmonella/fisiologia
12.
Infect Immun ; 63(8): 3054-61, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7622230

RESUMO

The actions of polymyxin B, rabbit polymorphonuclear lysosome extracts, 14 polycationic peptides (including defensin NP-2, cecropin P1, lactoferricin B, and active peptides from cationic protein 18 and bactenecin), EDTA, and Tris on Brucella spp. were studied, with other gram-negative bacteria as controls. Brucella spp. were comparatively resistant to all of the agents listed above and bound less polymyxin B, and their outer membranes (OMs) were neither morphologically altered nor permeabilized to lysozyme by polymyxin B concentrations, although both effects were observed for controls. EDTA and peptides increased or accelerated the partition of the hydrophobic probe N-phenyl-naphthylamine into Escherichia coli and Haemophilus influenzae OMs but had no effect on Brucella OMs. Since Brucella and H. influenzae OMs are permeable to hydrophobic compounds (G. Martínez de Tejada and I. Moriyón, J. Bacteriol. 175:5273-5275, 1993), the results show that such unusual permeability is not necessarily related to resistance to polycations. Although rough (R) B. abortus and B. ovis were more resistant than the controls were, there were qualitative and quantitative differences with smooth (S) brucellae; this may explain known host range and virulence differences. Brucella S-lipopolysaccharides (LPSs) had reduced affinities for polycations, and insertion of Brucella and Salmonella montevideo S-LPSs into the OM of a Brucella R-LPS mutant increased and decreased, respectively, its resistance to cationic peptides. The results show that the core lipid A of Brucella LPS plays a major role in polycation resistance and that O-chain density also contributes significantly. It is proposed that the features described above contribute to Brucella resistance to the oxygen-independent systems of phagocytes.


Assuntos
Brucella/efeitos dos fármacos , Defensinas , Proteínas/farmacologia , Proteínas de Xenopus , Peptídeos Catiônicos Antimicrobianos , Membrana Celular/efeitos dos fármacos , Resistência a Medicamentos , Ácido Edético/farmacologia , Escherichia coli/efeitos dos fármacos , Lipopolissacarídeos/química , Meliteno/farmacologia , Peptídeos/farmacologia , Polimixina B/farmacologia , Yersinia enterocolitica/efeitos dos fármacos
13.
Mol Microbiol ; 22(5): 895-908, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8971711

RESUMO

Bordetella pertussis and Bordetella bronchiseptica contain nearly identical BvgAS signal-transduction systems that mediate a biphasic transition between virulent (Bvg+) and avirulent (Bvg-) phases. In the Bvg+ phase, the two species express a similar set of adhesins and toxins, and in both organisms the transition to the Bvg- phase occurs in response to the same environmental signals (low temperature or the presence of nicotinic acid or sulphate anion). These two species differ, however, with regard to Bvg(-)-phase phenotypes, host specificity, the severity and course of the diseases they cause, and also potentially in their routes of transmission. To investigate the contribution of the virulence-control system to these phenotypic differences, we constructed a chimeric B. bronchiseptica strain containing bvgAS from B. pertussis and compared it with wild-type B. bronchiseptica in vitro and in vivo. The chimeric strain was indistinguishable from the wild type in its ability to express Bvg(+)- and Bvg(-)- phase-specific factors. However, although the chimeric strain responded to the same signals as the wild type, it differed dramatically in sensitivity to these signals; significantly more nicotinic acid or MgSO4 was required to modulate the chimeric strain compared with the wild-type strain. Despite this difference in signal sensitivity, the chimeric strain was indistinguishable from the wild type in its ability to cause respiratory-tract infections in rats, indicating that the bvgAS loci of B. pertussis and B. bronchiseptica are functionally interchangeable in vivo. By exchanging discrete fragments of bvgAS, we found that the periplasmic region of BvgS determines signal sensitivity.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Bordetella/microbiologia , Bordetella bronchiseptica/patogenicidade , Bordetella pertussis/patogenicidade , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Animais , Proteínas de Bactérias/genética , Infecções por Bordetella/patologia , Bordetella bronchiseptica/genética , Bordetella pertussis/genética , Feminino , Pulmão/microbiologia , Sulfato de Magnésio/farmacologia , Niacina/farmacologia , Fenótipo , Ratos , Ratos Wistar , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Transcrição/genética , Virulência
14.
Infection ; 26(5): 270-3, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9795782

RESUMO

The DNA fingerprints of 170 human isolates and ten ovine isolates of Bordetella parapertussis were examined by arbitrarily-primed PCR/RAPD with 29 primers. Based on this technique, all the human isolates appear highly genetically homogeneous. The ovine isolates could be distinguished from human isolates and they showed diversity among themselves. Therefore, human isolates of B. parapertussis are a highly clonal group adapted to infect humans and they are distinct from polymorphic ovine isolates.


Assuntos
Infecções por Bordetella/microbiologia , Bordetella/classificação , Impressões Digitais de DNA , Técnica de Amplificação ao Acaso de DNA Polimórfico , Doenças dos Ovinos/microbiologia , Animais , Bordetella/genética , Bordetella/isolamento & purificação , Infecções por Bordetella/veterinária , DNA Bacteriano/análise , Humanos , Nova Zelândia , Escócia , Ovinos , Especificidade da Espécie
15.
Infect Immun ; 66(6): 2762-8, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9596745

RESUMO

In Bordetella species, the BvgAS sensory transduction system mediates an alteration between the Bvg+ phase, characterized by expression of adhesins and toxins, and the Bvg- phase, characterized by the expression of motility and coregulated phenotypes in Bordetella bronchiseptica and by the expression of vrg loci in Bordetella pertussis. Since there is no known environmental or animal reservoir for B. pertussis, the causative agent of whooping cough, it has been assumed that this phenotypic alteration must occur within the human host during infection. Consistent with this hypothesis was the observation that a B. pertussis mutant, SK6, containing a TnphoA insertion mutation in a Bvg-repressed gene (vrg6) was defective for tracheal and lung colonization in a mouse model of respiratory infection (D. T. Beattie, R. Shahin, and J. Mekalanos, Infect. Immun. 60:571-577, 1992). This result was inconsistent, however, with the observation that a Bvg+ phase-locked B. bronchiseptica mutant was indistinguishable from the wild type in its ability to establish a persistent respiratory infection in rabbits and rats (P. A. Cotter and J. F. Miller, Infect. Immun. 62:3381-3390, 1994; B. J. Akerley, P. A. Cotter, and J. F. Miller, Cell 80:611-620, 1995). To directly address the role of Bvg-mediated signal transduction in B. pertussis pathogenesis, we constructed Bvg+ and Bvg- phase-locked mutants and compared them with the wild type for their ability to colonize the respiratory tracts of mice. Our results show that the Bvg+ phase of B. pertussis is necessary and sufficient for respiratory infection. By constructing a strain with a deletion in the bvgR regulatory locus, we also show that ectopic expression of Bvg- phase phenotypes decreases the efficiency of colonization, underscoring the importance of Bvg-mediated repression of gene expression in vivo. Finally, we show that the virulence defect present in strain SK6 cannot be attributed to the vrg6 mutation. These data contradict an in vivo role for the Bvg- phase of B. pertussis.


Assuntos
Proteínas de Bactérias/genética , Bordetella pertussis/patogenicidade , Fatores de Transcrição/genética , Coqueluche/etiologia , Animais , Bordetella bronchiseptica/patogenicidade , Bordetella pertussis/genética , Pulmão/microbiologia , Camundongos , Mutação , Fenótipo , Especificidade da Espécie , Traqueia/microbiologia
16.
Mol Cell Neurosci ; 17(5): 793-810, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11358479

RESUMO

Inclusion body myositis (sIBM) is the most common disorder of skeletal muscle in aged humans. It shares biochemical features with Alzheimer's disease, including congophilic deposits, which are immunoreactive for beta-amyloid peptide (Abeta) and C'-terminal betaAPP epitopes. However, the etiology of myofiber loss and the role of intracellular Abeta in IBM is unknown. Here we report correlative evidence for apoptotic cell death in myofibers of IBM patients that exhibit pronounced Abeta deposition. HSV-1-mediated gene transfer of Abeta(42) into cultured C2C12 myotubes resulted in a 12.6-fold increase in dUTP-labeled and condensed nuclei over nonexpressing myotubes (P < 0.05). The C'-terminal betaAPP domain C99 also induced myotube apoptosis, but to a significantly lesser extent than Abeta. Apoptosis specific to Abeta-expressing myotubes was also demonstrated through DNA fragmentation, decreased mitochondrial function and the loss of membrane phospholipid polarity. Myotubes laden with Abeta(42), but not other transgene products, developed cytoplasmic inclusions consisting of fibrillar material. Furthermore, injection of normal mouse gastrocnemius muscle with HSV-encoding Abeta cDNA resulted in TUNEL-positive myofibers with pyknotic nuclei. We conclude that Abeta is sufficient to induce apoptosis in myofibers both in vivo and in vitro and suggest it may contribute to myofiber loss and muscle dysfunction in patients with IBM.


Assuntos
Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Apoptose/genética , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Miosite de Corpos de Inclusão/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Células Cultivadas/metabolismo , Células Cultivadas/patologia , Células Cultivadas/ultraestrutura , Fragmentação do DNA/genética , DNA Complementar/farmacologia , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Microscopia Eletrônica , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Miosite de Corpos de Inclusão/genética , Miosite de Corpos de Inclusão/fisiopatologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Estrutura Terciária de Proteína/genética , Simplexvirus/genética
17.
Diagnóstico (Perú) ; 17(3): 84-8, mar. 1986. tab
Artigo em Espanhol | LILACS | ID: lil-64493

RESUMO

Se estudió la eficacia y tolerancia del clorhidrato de prazosina en 192 pacientes, 90 hombres, 102 mujeres cuyas edades variaron entre 29 y 65 años portadores de HAE en 10 hospitales de Lima metropolitana y 1 de provincias agrupados en 3 categorías según los criterios de la OMS - 1962. Después de 1 semana de placebo se hicieron controles de presión arterial (PA) supina cardíaca (FC) al finalizar la 1ra., 2da., 4ta., 6ta., 8va. semana. La dosis fue de 0.5 mg b.i.d. tomando la primera al acostarse. A juicio del investigador y a partir de la 6ta. semana se añadió un diurético (52 casos la mayoría usó clortalidona, o hidroclorotiazida y sólo 4 casos furosemida. al finalizar la 8va. semana se encontró una respuesta "normalizada" (PAD 90 mmHg) en 100% de los hipertensos leves, 85% de los moderados y 60% de los severos, y una respuesta "satisfactoria" (PAD 100 mmHg) en 98% de los hipertensos moderados y en 90% de severos. Los efectos más frecuentes fueron: cefalea, mares y palpitaciones. No se observó ningún caso de "fenómeno de la primera dosis". De acuerdo al estudio, la prazosina es una droga útil en el tratamiento de la HAE cualquiera sea su severidad, teniendo en cuenta su baja toxicidad, su amplio rango de sodificación y su potenciación combinada con diuréticos. Si a esto le agregamos su carencia de "fenómeno de rebote" y de efectos sobre la líbido, así como su favorable acción sobre las dislipoproteinas al elevar el HDL. Se concluye que la prazosina es una droga con amplias ventajas en el manejo de los hipertensos


Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Hipertensão/tratamento farmacológico , Prazosina/administração & dosagem , Ensaios Clínicos como Assunto , Prazosina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA