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1.
Biochimie ; 179: 101-112, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32926968

RESUMO

The tyrocidines and analogues are cationic cyclodecapeptides [cyclo (D-Phe1-L-Pro2-L-(Phe3/Trp3)-D-(Phe4/Trp4)-L-Asn5-L-Gln6-L-(Tyr7/Phe7/Trp7)-L-Val8-L-(Orn9/Lys9)-L-Leu10], produced together with the neutral linear pentadecapeptide gramicidins, in the antibiotic tyrothricin complex by Brevibacillus parabrevis. Despite discovery 80 years ago, it was still uncertain whether these peptides are secreted or sequestered intracellularly. We resolved this by utilising high resolution electrospray mass spectrometry to confirm the predominantly intracellular sequestration of the peptides in the tyrothricin complex. A "peptidomics" approach allowed us to map the intracellular production of 16 cyclodecapeptides and 6 gramicidins over 16 days of culturing. Gramicidin production remained relatively constant, with Val-gramicidin A the predominant analogue produced throughout the 16 day fermentation period. The tyrothricin cyclodecapeptides have four variable positions and there was a culturing time related shift from the Phe-rich A analogues, containing a L-Phe3-D-Phe4 aromatic dipeptide unit, to the Trp-rich C analogues with L-Trp3-D-Trp4. For the other variable aromatic residue position, Tyr7 was preferentially incorporated above Trp7, with a minor incorporation of Phe7 over the whole culturing period. For the variable basic amino acid residue, there was time-sensitive shift from Orn9 to Lys9 incorporation. Modulation of the cyclodecapeptide profile over time does not correlate with the reported non-ribosomal peptide synthetase affinity, specifically for Trp in the variable aromatic residue positions, indicating additional supply-demand control in the cyclodecapeptides production by B. parabrevis. These novel observations are not only of importance for production and purification of selected peptide analogues from the tyrothricin complex, but also for insight into microbial control of non-ribosomal peptide production that extends beyond the peptide synthetase machinery.


Assuntos
Antibacterianos/biossíntese , Antibacterianos/química , Brevibacillus/crescimento & desenvolvimento , Brevibacillus/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos , Tirotricina/biossíntese , Tirotricina/química , Substituição de Aminoácidos , Antibacterianos/metabolismo , Brevibacillus/citologia , Fermentação , Fatores de Tempo
2.
Int J Clin Pract ; 72(12): e13272, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30329199

RESUMO

OBJECTIVE: The aim of this multi-centre, randomised, double-blind, placebo-controlled trial was to compare the efficacy and safety of the fixed combination of 0.5 mg tyrothricin, 1.0 mg benzalkonium chloride, and 1.5 mg benzocaine (study drug marketed as Dorithricin® ) in repeat dosing for 3 days to match placebo lozenges in the treatment of acute pharyngitis in adults. METHODS: Patients (pts, aged ≥18 years) with acute pharyngitis, ie, non-streptococcal sore throat and moderate-to-severe pain (intensity NRS ≥ 7; VAS ≥ 50) were assigned to study drug (n = 160) or matching placebo (n = 161). Efficacy was assessed by investigator for 2 hours post initial dose (p.i.d.), and 3 days later (Visit 2). Primary efficacy endpoint was the complete resolution of throat pain and difficulty in swallowing at Visit 2 (3 days p.i.d.). Safety and local tolerability were also assessed. RESULTS: Seventy-two hours (p.i.d.), complete resolution of throat pain and difficulty in swallowing were achieved by 44.6% patients on study drug compared with 27.2% patients on placebo (difference 17.4% (CI [5.8%; 29.7%]; 64% improvement [GEE, P = 0.0022]). Until 2 hours p.i.d., reduction in symptoms was better with study drug (P < 0.005). Treatment satisfaction was higher with study drug (patients'/investigators' assessment (78.9%/78.9% vs 55.0%/55.6% for placebo) and was well tolerated, overall safety profile was comparable to placebo. CONCLUSION: The strength of this randomised controlled trial lies in the endpoint of complete remission after 3 days p.i.d., especially in the light of other trials addressing acute pharyngitis. The results of this study show a significant benefit of the study drug over placebo in the treatment of acute pharyngitis. Local treatment with the fixed combination (0.5 mg tyrothricin, 1.0 mg benzalkonium chloride, and 1.5 mg benzocaine) provides a rapid analgesic effect and is effective in relieving both severe throat pain as well as difficulty in swallowing associated with acute pharyngitis leading to a 64% improved complete remission within 72 hours. The triple active combination is a suitable treatment option for patients in the self-management of acute pharyngitis and sore throat. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03323528.


Assuntos
Compostos de Benzalcônio/uso terapêutico , Benzocaína/uso terapêutico , Dor/tratamento farmacológico , Faringite/tratamento farmacológico , Tirotricina/uso terapêutico , Doença Aguda , Administração Oral , Adulto , Deglutição , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Satisfação do Paciente , Faringite/complicações , Resultado do Tratamento , Adulto Jovem
3.
Arch Dermatol Res ; 309(3): 159-167, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28180934

RESUMO

Propionibacterium acnes: (P. acnes) produce Porphyrins; however, fluorescence measurement of Porphyrins from Ultraviolet-A (UVA) images has failed to establish a correlation. Acne clinical research and imaging has ignored the spectral excitation-emission characteristics and the exact pattern of the Porphyrins synthesized by P. acnes. In this exploratory study, for the first time, the possible relationships of Coproporphyrin III (CpIII) and Protoporphyrin IX (PpIX) fluorescence as well as acne lesion-specific inflammation measurements with clinical signs of acne are investigated. Furthermore, the sensitivity of these measurements in tracking and differentiating the known treatment effects of Benzoyl Peroxide (BPO) 5%, and combination of Clindamycin + BPO are also evaluated. Comedonal and papulopustular lesions identified by investigators during a live assessment of 24 mild-to-severe acne subjects were compared with fluorescence and inflammation measurements obtained from analysis of VISIA®-CR images. CpIII fluorescence spots showed a strong correlation (r = 0.69-0.83), while PpIX fluorescence spots showed a weak correlation (r = 0.19-0.27) with the investigators' comedonal lesion counts. A strong correlation was also observed between the investigators' papulopustular lesion counts and acne lesion-specific inflammation (r = 0.76). Our results suggest that CpIII fluorescence and acne lesion-specific-inflammation measurement can provide objective indication of comedonal and papulopustular acne severity, respectively. Furthermore, these measurements may be more sensitive and specific in evaluating treatment effects and early signs of acne lesion progression compared to investigators' lesion counts.


Assuntos
Acne Vulgar/diagnóstico por imagem , Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Coproporfirinas/farmacologia , Fármacos Dermatológicos/uso terapêutico , Imagem Óptica/métodos , Protoporfirinas/farmacologia , Índice de Gravidade de Doença , Tirotricina/uso terapêutico , Adolescente , Adulto , Peróxido de Benzoíla/uso terapêutico , Clindamicina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Porfirinas/metabolismo , Propionibacterium acnes/metabolismo , Adulto Jovem
4.
Pharmazie ; 71(6): 299-305, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27455547

RESUMO

The antimicrobial agent tyrothricin is a representative of the group of antimicrobial peptides (AMP). It is produced by Bacillus brevis and consists of tyrocidines and gramicidins. The compound mixture shows activity against bacteria, fungi and some viruses. A very interesting feature of AMPs is the fact, that even in vitro it is almost impossible to induce resistances. Therefore, this class of molecules is discussed as one group that could serve as next generation antibiotics and overcome the increasing problem of bacterial resistances. In daily practice, the application of tyrothricin containing formulations is relatively limited: It is used in sore throat medications and in agents for the healing of infected superficial and small-area wounds. However, due to the broad spectrum antimicrobial activity and the low risk of resistance development it is worth to consider further fields of application.


Assuntos
Antibacterianos/uso terapêutico , Dermatopatias Infecciosas/tratamento farmacológico , Tirotricina/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antivirais/farmacologia , Humanos , Dermatopatias Infecciosas/microbiologia , Relação Estrutura-Atividade , Tirotricina/efeitos adversos , Tirotricina/farmacologia , Infecção dos Ferimentos/microbiologia
6.
J Microbiol Biotechnol ; 26(5): 953-8, 2016 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-26907760

RESUMO

Chitosan-based film-forming gel is regarded as a promising vehicle for topical delivery of antimicrobial agents to skin wounds, since it protects from microbial infection and the cationic polymer itself possesses antibacterial activity. In this study, possible synergistic interaction against common skin pathogens between the cationic polymer and tyrothricin (TRC), a cyclic polypeptide antibiotic, was investigated, by determining the concentration to inhibit 90% of bacterial isolates (MIC). The addition of the polysaccharide to TRC dramatically reduced the MIC values of TRC by 1/33 and 1/4 against both methicillin-resistant and methicillinsusceptible Staphylococcus aureus, respectively. The synergism of TRC and chitosan combination against both strains was demonstrated by the checkerboard method, with a fractional inhibitory concentration index below 0.5. Moreover, co-treatment of TRC and chitosan exhibited antibacterial activity against Pseudomonas aeruginosa, due to the antibacterial activity of chitosan, whereas TRC itself did not inhibit the gram-negative bacterial growth. These findings suggested that the use of chitosan-based film for topical delivery of TRC could be an alternative to improve TRC antimicrobial activity against strains that are abundant in skin wounds.


Assuntos
Quitosana/administração & dosagem , Quitosana/química , Pele/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Tirotricina/administração & dosagem , Tirotricina/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Combinação de Medicamentos , Sinergismo Farmacológico , Géis/administração & dosagem , Géis/química , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Viabilidade Microbiana/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico
7.
Skin Pharmacol Physiol ; 29(1): 1-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26458265

RESUMO

BACKGROUND/AIMS: Antibiotic-induced drug resistance requires new approaches in topical acne treatment. Tyrothricin is known to produce no resistance. In this study, it was tested for the first time in topical acne treatment. The efficacy and tolerability of topical tyrothricin 0.1% was evaluated. METHODS: A randomized, active comparator-controlled, exploratory, observer-blind clinical study was conducted in 24 patients with acne papulopustulosa. Randomization on a split-face was either tyrothricin versus clindamycin + benzoyl peroxide (BPO) (n = 12) or tyrothricin versus BPO 5% (n = 12). The main outcome was change in inflammatory and noninflammatory lesion counts. RESULTS: The mean differences in inflammatory lesion counts from baseline were -12.3 (95% CI: -20.5 to -4.1) in clindamycin + BPO, -10.2 (95% CI: -15.3 to -5.0) in BPO 5%, and -7.7 (95% CI: -11.7 to -3.7) in tyrothricin. Tyrothricin reduced noninflammatory lesions (mean difference: -6.5 (95% CI: -11.6 to -1.4) and caused less product-related adverse events (n = 31) compared to BPO (n = 37) and clindamycin + BPO (n = 20). CONCLUSION: The results indicate that tyrothricin might be a candidate for treating acne and it seems to be more tolerable than both comparator treatments.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Tirotricina/uso terapêutico , Administração Tópica , Adolescente , Adulto , Peróxido de Benzoíla/uso terapêutico , Clindamicina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Masculino , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
8.
Klin Khir ; (7): 44-6, 2015 Jul.
Artigo em Ucraniano | MEDLINE | ID: mdl-26591219

RESUMO

Examined 22 patients with diabetes mellitus (DM) type II of neuropathic form of diabetic foot syndrome (DFS). In 12 patients (comparison group) local povidone-iodine was used main in 10 (study group), except povidone-iodine, in the phase of exudation used tyrothricin in gel form, the granulation and epithelization phase, after cleaning the wounds, were injected intradermally 1 ml of injecting material for skin regeneration Lacerta. Trophic defects in 9 (90%) patients of the main group during the observation period healed completely, in the comparison group complete healing of the ulcer reached in 2 (16.7%) patients, the rest-wounds, although purified, however, were lethargic granulation, epithelization occurred very slowly. Consequently, the use of the proposed method allows to achieve more rapid healing of trophic ulcers that do not heal continued in patients of neuropathic forms of DFS.


Assuntos
Fatores Biológicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Protaminas/uso terapêutico , Reepitelização/efeitos dos fármacos , Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Diabetes Mellitus Tipo 2/patologia , Pé Diabético/patologia , Neuropatias Diabéticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povidona-Iodo/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Tirotricina/uso terapêutico
9.
Arch Pharm Res ; 38(2): 229-38, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24715576

RESUMO

The objective of this study was to evaluate the healing effects of a chitosan-based, film-forming gel containing tyrothricin (TYR) in various rat wound models, including burn, abrasion, incision, and excision models. After solidification, the chitosan film layer successfully covered and protected a variety of wounds. Wound size was measured at predetermined timepoints after wound induction, and the effects of the film-forming gel were compared with negative (no treatment) and positive control groups (commercially available sodium fusidate ointment and TYR gel). In burn, abrasion and excision wound models, the film-forming gel enabled significantly better healing from 1 to 6 days after wound induction, compared with the negative control. Importantly, the film-forming gel also enabled significantly better healing compared with the positive control treatments. In the incision wound model, the breaking strength of wound strips from the group treated with the film-forming gel was significantly increased compared with both the negative and positive control groups. Histological studies revealed advanced granulation tissue formation and epithelialization in wounds treated with the film-forming gel. We hypothesize that the superior healing effects of the film-forming gel are due to wound occlusion, conferred by the chitosan film. Our data suggest that this film-forming gel may be useful in treating various wounds, including burn, abrasion, incision and excision wounds.


Assuntos
Antibacterianos/uso terapêutico , Quitosana/química , Portadores de Fármacos/química , Tirotricina/uso terapêutico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Modelos Animais de Doenças , Feminino , Géis , Estrutura Molecular , Ratos Sprague-Dawley , Tirotricina/administração & dosagem
10.
Eur J Clin Microbiol Infect Dis ; 33(2): 233-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23955154

RESUMO

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of 2 µg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4 µg/ml). Nearly all isolates (≥ 99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 µg/ml for ceftobiprole and 1 µg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 µg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 µg/ml, the MIC90 values were 2 µg/ml for teicoplanin, 0.5 µg/ml for daptomycin, and 0.5 µg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 µg/ml (2, 0.06, and 0.12 µg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n = 1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 µg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Cefalosporinas/farmacologia , Monitoramento Epidemiológico , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Quinolonas/farmacologia , Infecções Estafilocócicas/microbiologia , Taiwan , Tirotricina/farmacologia
11.
Pharmazie ; 69(11): 838-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25985581

RESUMO

Tyrothricin, an antimicrobial peptide combination produced by Bacillus brevis consisting of gramicidins and tyrocidins commands broad antimicrobial activity against gram-positive bacteria and some yeasts in vitro. The polypeptide and its components have been used therapeutically for about 60 years in the local treatment of infected skin and infected oro-pharyngeal mucous membranes. Though older studies suggest that resistance development of originally susceptible microorganisms towards tyrothricin is a rare event, data concerning recent state of resistance are lacking. In the present in vitro study the susceptibility to tyrothricin of clinical isolates of bacterial and yeast origin from superficial swabs of the skin and mucous membranes of outpatients and inpatients obtained from clinical material in the second half of the year 2003 was determined. Using a microdilution assay, the minimum inhibitory concentration (MIC and MIC90, defined as the concentration that inhibits at least 90 percent of the tested strains) of 20 strains each of Staphylococcus aureus of the variety MSSA (susceptible to methicillin), Staphylococcus aureus of the variety MRSA (methicillin resistant), Staphylococcus haemolyticus, Streptococcus pyogenes, Enterococcus faecalis, Corynebacterium spec., Candida albicans and Candida parapsilosis was determined. All of the tested gram-positive bacteria turned out to be highly susceptible to tyrothricin with MICs ≤ 4mg/l. The tested yeast strains were susceptible to the polypeptide antibiotic as well, but (with MICs of 16 mg/l and 32 mg/l, respectively) to a lesser extent. No acquired resistance of the tested strains was determined, indicating that the risk of resistance development against topically applied tyrothricin is only marginal, if there is any at all. Thus, long-term-, i.e. decade-long use of topically applied tyrothricin and its components in the local treatment of infected skin does not pose a major risk with respect to acquired resistance of originally susceptible gram-positive bacteria and yeasts, not even in the case of Staphylococcus aureus, both with MSSA and MRSA strains. The broad anti-bacterial and anti-fungal activity of tyrothricin combined with its lacking risk for resistance development make the antimicrobial peptide a valuable addition to our therapeutic armamentarium in the treatment of infected skin.


Assuntos
Antibacterianos/efeitos adversos , Candida/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Tirotricina/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Micoses/microbiologia , Tirotricina/uso terapêutico
12.
Microbiology (Reading) ; 159(Pt 10): 2200-2211, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23963303

RESUMO

A group of non-ribosomally produced antimicrobial peptides, the tyrocidines from the tyrothricin complex, have potential as antimicrobial agents in both medicine and industry. Previous work by our group illustrated that the more polar tyrocidines rich in Trp residues in their structure were more active toward Gram-positive bacteria, while the more non-polar tyrocidines rich in Phe residues had greater activity toward Plasmodium falciparum, one of the major causative pathogens of malaria in humans. Our group also found that the tyrocidines have pronounced antifungal activity, dictated by the primary sequence of the tyrocidine. By simply manipulating the Phe or Trp concentration in the culture medium of the tyrothricin producer, Bacillus aneurinolyticus ATCC 10068, we were able to modulate the production of subsets of tyrocidines, thereby tailoring the tyrothricin complex to target specific pathogens. We optimized the tailored tyrothricin production using a novel, small-scale, high-throughput deep 96-well plate culturing method followed by analyses of the peptide mixtures using ultra-performance liquid chromatography linked to mass spectrometry. We were able to gradually shift the production profile of the tyrocidines and analogues, as well as the gramicidins between two extremes in terms of peptide subsets and peptide hydrophobicity. This study demonstrated that tyrothricin peptide subsets with targeted activity can be efficiently produced by simple manipulation of the aromatic amino acid profile of the culture medium.


Assuntos
Anti-Infecciosos/metabolismo , Bacillus/metabolismo , Tirotricina/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Cromatografia Líquida , Meios de Cultura/química , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectrometria de Massas , Fenilalanina/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Triptofano/metabolismo , Tirotricina/química , Tirotricina/farmacologia
13.
Skin Pharmacol Physiol ; 26(1): 52-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23183356

RESUMO

BACKGROUND: Topical preparations are a common treatment for superficial acute wounds, which at the least do not interfere with healing and ideally result in enhanced wound healing irrespective of microbial colonization. OBJECTIVE: To examine the effects of a topical antimicrobial gel and its vehicle on the wound healing of standardized, superficial abrasions. METHODS: Thirty-three healthy volunteers were enrolled in a double-blinded, randomized, intraindividual comparison study. Three standardized, superficial abrasions were induced on their forearms. A tyrothricin 0.1% gel (Tyrosur® gel; Engelhard Arzneimittel GmbH & Co. KG, Niederdorfelden, Germany) and its vehicle were randomly applied to two of the test areas, and one lesion remained untreated. RESULTS: A significant improvement of wound healing was seen with both tyrothricin 0.1% gel and its corresponding vehicle in the clinical assessment. The mean area under the curve (AUC) of wound healing scores was the same for both preparations and the mean reepithelization scores were comparable at all test points over the entire 12 days. A lower mean AUC representing less reepithelization was found for the untreated test fields. CONCLUSION: The use of tyrothricin 0.1% gel and its corresponding vehicle resulted in statistically significant improved wound healing with an earlier onset of healing in particular. Based on these results obtained using an abrasive wound model, it can be concluded that the addition of tyrothricin 0.1% to the gel vehicle did not interfere with the improved wound healing seen with the vehicle alone.


Assuntos
Antibacterianos/administração & dosagem , Anti-Infecciosos Locais/administração & dosagem , Pele/efeitos dos fármacos , Tirotricina/administração & dosagem , Cicatrização/efeitos dos fármacos , Adulto , Método Duplo-Cego , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Pele/lesões , Resultado do Tratamento , Adulto Jovem
14.
J Antimicrob Chemother ; 65(12): 2598-601, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20861141

RESUMO

OBJECTIVE: The rising occurrence of drug-resistant pathogens accentuates the need to identify novel antibiotics. We wanted to identify new scaffolds for drug discovery by repurposing FDA-approved drugs against Acinetobacter baumannii, an emerging Gram-negative nosocomial drug-resistant pathogen. MATERIALS AND METHODS: In this study, we screened 1040 FDA-approved drugs against drug-susceptible A. baumannii ATCC 17978 and drug-resistant A. baumannii BAA-1605. RESULTS AND DISCUSSION: Twenty compounds exhibited significant antimicrobial activity (MIC ≤8 mg/L) against ATCC 17978 while only five compounds showed such activity against BAA-1605. Among the most notable results, tyrothricin, a bactericidal antibiotic typically active only against Gram-positive bacteria, exhibited equipotent activity against both strains. CONCLUSION: The paucity of identified compounds active against drug-resistant A. baumannii exemplifies its ability to resist antimicrobials as well as the resilience of drug-resistant Gram-negative pathogens. Repurposing of approved drugs is a viable alternative to de novo drug discovery and development.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Descoberta de Drogas/métodos , Farmacorresistência Bacteriana Múltipla , Tirotricina/farmacologia , Infecções por Acinetobacter/microbiologia , Aprovação de Drogas , Humanos , Testes de Sensibilidade Microbiana , Estados Unidos , United States Food and Drug Administration
15.
J Biomol Screen ; 12(8): 1102-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18087073

RESUMO

The previously described Bacillus subtilis reporter strain BAU-102 is capable of detecting cell wall synthesis inhibitors that act at all stages of the cell wall synthesis pathway. In addition, this strain is capable of detecting compounds with hydrophobic/surfactant activity and alternative mechanisms of cell wall disruption. BAU-102 sequesters preformed beta-gal in the periplasm, suggesting leakage of beta-gal as the means by which this assay detects compound activities. A model is proposed according to which beta-gal release by BAU-102 reflects activation of pathways leading to autolysis. The authors also report a simplified high-throughput assay using BAU-102 combined with the fluorogenic substrate N-methylumbelliferyl-beta-D-galactoside as a single reagent. Cell wall inhibitors release beta-gal consistently only after 60 min of incubation, whereas compounds with surfactant activity show an almost immediate release. A high-throughput screen of a 480-compound library of known bioactives yielded 8 compounds that cause beta-gal release. These results validate the BAU-102 assay as an effective tool in antimicrobial drug discovery.


Assuntos
Antibacterianos/análise , Avaliação Pré-Clínica de Medicamentos/métodos , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacteriólise/efeitos dos fármacos , Detergentes/farmacologia , Genes Reporter , Periplasma/efeitos dos fármacos , Periplasma/enzimologia , Tirotricina/farmacologia , Vancomicina/farmacologia , beta-Galactosidase/metabolismo
16.
Aliment Pharmacol Ther ; 24(4): 687-94, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16907901

RESUMO

BACKGROUND: Among the randomized controlled trials evaluating the effect of pharyngeal anaesthesia only some suggest benefit. Spray is irritating for some people and leaves bitter taste in the throat. We hypothesized that delivering the local anaesthetic as a sucking lozenge would benefit the patients in terms of decreasing anxiety and will improve procedure performance and patient tolerance. AIM: To determine whether benzocaine/tyrothricin sucking lozenges with conscious sedation is superior to conscious sedation alone, with respect to procedure performance and tolerance in patients undergoing upper endoscopy. METHODS: One hundred and seventy-four adult patients undergoing upper endoscopy with conscious sedation completed the study. They were randomized to receive sucking lozenge containing benzocaine or placebo before the procedure. Patients were asked to rate prestudy anxiety, tolerance for topical pharyngeal anaesthesia, comfort during endoscopy, degree of difficulty of intubation, postprocedure throat discomfort and willingness to undergo subsequent examinations using a 10-cm visual analogue scale. Endoscopists were asked to estimate the ease of oesophageal intubation and procedure performance. RESULTS: No significant statistical differences regarding all the points studied were found between the groups. CONCLUSIONS: Topical pharyngeal anaesthesia with benzocaine/tyrothricin lozenges with conscious sedation has no advantages over conscious sedation alone in patients undergoing upper endoscopy.


Assuntos
Anestésicos Locais/administração & dosagem , Benzocaína/administração & dosagem , Sedação Consciente/métodos , Endoscopia Gastrointestinal/métodos , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos Locais/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos , Tirotricina/administração & dosagem
17.
J Endod ; 32(1): 17-23, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16410062

RESUMO

The study was aimed at comparing the efficacy of disinfection of root canals with periapical radiolucencies when treated with either antibiotics/steroid medicaments (Ledermix or Septomixine) or a calcium hydroxide paste (Calasept). Microbiological samples were taken before and after two-visit endodontic treatment from 88 canals with apical periodontitis. All of the canals but one (87 of 88) had cultivable growth before treatment. After dressing with Ledermix, Septomixine, or Calasept, the percentages of canals remained with positive growth were 48% (13 of 27), 31% (8 of 26), and 31% (11 of 35), respectively. The chi(2) tests showed there were no significant differences in the number of canals with positive growth or mean colony forming units counts after instrumentation, irrigation and dressing. In the Ledermix group, 38 strains of bacteria were recovered. The Septomixine group had 25 strains, and the Calasept group had 25 strains. Gram-positive facultative anaerobic cocci (including staphylococci and streptococci) were more prevalent than the Gram-negative obligate anaerobic rods after treatment in all three groups. Similarities in the reduced number of canals with residual growth, and the prevalence of Gram-positive facultative anaerobic cocci suggest that the use of different inter-appointment dressings produced similar microbiological outcomes. However, factors other than the antimicrobial effectiveness of intracanal medicaments may also be responsible for the results observed.


Assuntos
Bactérias Anaeróbias/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Periodontite Periapical/microbiologia , Irrigantes do Canal Radicular/farmacologia , Antibacterianos/farmacologia , Bactérias Anaeróbias/isolamento & purificação , Cloreto de Cálcio , Hidróxido de Cálcio/farmacologia , Contagem de Colônia Microbiana , Demeclociclina/farmacologia , Combinação de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Neomicina/farmacologia , Polimixina B/farmacologia , Cloreto de Potássio , Bicarbonato de Sódio , Cloreto de Sódio , Triancinolona Acetonida/farmacologia , Tirotricina/farmacologia
18.
Pharmazie ; 59(11): 864-8, 2004 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-15587588

RESUMO

BACKGROUND AND OBJECTIVES: The efficacy and tolerance of an antiseptic wound powder based on the antibiotic tyrothricin was investigated in a prospective, randomized multicenter trial in patients with posttraumatic and surgical cutaneous lesions. PATIENTS AND METHODS: In 5 centers, 131 male and female patients from 18-85 years were included with posttraumatic or surgical cutaneous lesions with infection or in danger of infection (area > or = 200 mm2). In a double-blind study, tyrothricin (n = 62; 0.1 g tyrothricin per 100 g of vehicle) or placebo powder (n = 69) was applied to the wound twice daily for 9 days. The primary aim was to evaluate the average daily reduction of the radius from the lesion area between the start and end of the randomized treatment (alpha = 0.025; one-sided). Secondly, a wound index (range 0-15) was calculated from the assessments of rubor, crusting, exudation, pain and functional impairment. RESULTS: The treatment groups were comparable at baseline. During randomized treatment, the radius of the lesions was reduced at an average of 0.55 +/- 0.31 mm/day (mean +/- SD) for tyrothricin and 0.47 +/- 0.30 mm/day for placebo (p = 0.016; one-sided; intention-to-treat data set). The wound index decreased at an average of 4.2 +/- 1.7 and 3.3 +/- 1.9 points for tyrothricin and placebo, respectively (p = 0.0048; one-sided). 4 adverse events occurred in each group. A causal relationship with the investigational drug could not be excluded in 3 of the placebo group. CONCLUSION: The results confirm the tendency to an acceleration of wound healing by tyrothricin powder (Tyrosur Powder) in case of infection or danger of infection. A superior efficacy compared to placebo was demonstrated. Due to its good tolerability and the absence of a systemic effects tyrothricin powder is appropriate for the treatment of superficial skin lesions.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Pele/lesões , Tirotricina/uso terapêutico , Ferimentos e Lesões/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/microbiologia , Pele/patologia , Infecção da Ferida Cirúrgica/prevenção & controle , Tirotricina/administração & dosagem , Tirotricina/efeitos adversos , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/microbiologia , Ferimentos e Lesões/patologia
19.
J. bras. ginecol ; 107(10): 385-7, out. 1997. tab, graf
Artigo em Português | LILACS | ID: lil-225448

RESUMO

Dezessete pacientes com patologia inflamatória vulvovaginal foram acompanhados com Malvaticin Ginecológico em um estudo aberto, no sexo feminino, näo comparativo, no Estado do Rio de Janeiro, visando avaliar à eficácia e a telerância do fármaco, composto de Quinosol, Tirotricina, Ácido lático e Hidrolato de Malva. Demonstrou ser ificaz e com uma tolerância excelente em 100 por cento dos casos


Assuntos
Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Ácido Láctico/uso terapêutico , Tirotricina/uso terapêutico , Vulvite/tratamento farmacológico , Vulvovaginite/tratamento farmacológico , Doenças dos Genitais Femininos
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