RESUMO
The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.
Assuntos
Anti-Infecciosos/sangue , Plaquetas/química , Plaquetas/microbiologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/classificação , Anti-Infecciosos/imunologia , Peptídeos Catiônicos Antimicrobianos/imunologia , Antiparasitários/imunologia , Antivirais/imunologia , Plaquetas/imunologia , Humanos , Ribonucleases/imunologiaRESUMO
PURPOSE: To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model. METHODS: An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05). RESULTS: Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751). CONCLUSION: The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.
Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/sangue , Metronidazol/administração & dosagem , Metronidazol/sangue , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Cromatografia Líquida , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Abstract Purpose: To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model. Methods: An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05). Results: Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751). Conclusion: The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.
Assuntos
Animais , Masculino , Ratos , Cicatrização/efeitos dos fármacos , Metronidazol/administração & dosagem , Metronidazol/sangue , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/sangue , Fatores de Tempo , Administração Tópica , Cromatografia Líquida , Ratos Wistar , Modelos Animais de DoençasAssuntos
Anti-Infecciosos/sangue , Quilotórax/patologia , Coinfecção/patologia , Infecções por HIV/complicações , Leishmaniose/patologia , Infecções por Mycobacterium não Tuberculosas/patologia , Enteropatias Perdedoras de Proteínas/patologia , Quilotórax/diagnóstico , Coinfecção/diagnóstico , Humanos , Leishmaniose/diagnóstico , Linfocintigrafia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Plasma/química , Enteropatias Perdedoras de Proteínas/diagnóstico , Radiografia Abdominal , Radiografia Torácica , América do Sul , Tomografia Computadorizada por Raios XRESUMO
The aim of this study was to determine the biopharmaceutical characteristics of oseltamivir carboxylate (OC) after pulmonary delivery. After OC bolus and intratracheal nebulization (NEB) in rats, blood was collected and bronchoalveolar lavages (BALs) were performed. Epithelial lining fluid (ELF) concentrations were estimated from BAL fluid. The area under the curve (AUC) ratio for ELF to plasma was 842 times higher after NEB than after intravenous (i.v.) administration, indicating that OC nebulization offers a biopharmaceutical advantage over i.v. administration.
Assuntos
Anti-Infecciosos/sangue , Oseltamivir/análogos & derivados , Administração por Inalação , Administração Intravenosa , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacocinética , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacocinética , Área Sob a Curva , Lavagem Broncoalveolar , Masculino , Oseltamivir/administração & dosagem , Oseltamivir/sangue , Oseltamivir/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Cigarette smoking is considered to be a major risk factor for periodontal disease, and the antimicrobial agent metronidazole is commonly used for treatment of periodontitis. The authors evaluated the effect of cigarette smoking on the bioavailability of metronidazole in plasma and saliva. METHODS: Thirteen smokers and 13 nonsmokers received a single oral dose of 750 milligrams of metronidazole. Study personnel collected blood and saliva samples at baseline and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 and 48 hours after metronidazole administration. The authors quantified plasmatic and salivary metronidazole concentrations by means of high-performance liquid chromatography, and they determined the pharmacokinetic parameters and analyzed them statistically by using the Mann-Whitney test and nonpaired t test (α = 5 percent). RESULTS: The authors detected a significant reduction in plasmatic metronidazole concentrations in smokers at 1 hour, 1.5 hours and 2 hours compared with nonsmokers (P < .05). They also found a significant reduction in the maximum concentration in plasma in smokers as compared with that of nonsmokers (P < .05). The authors observed no statistically significant differences in the salivary concentration or pharmacokinetics between the two groups, however (P > .05). CONCLUSION: Cigarette smoking interfered with the bioavailability of metronidazole in plasma but not in saliva. Practice Implications. The clinical significance of these findings needs to be investigated further to verify the effectiveness of metronidazole in smokers.
Assuntos
Anti-Infecciosos/sangue , Metronidazol/sangue , Saliva/metabolismo , Fumar/metabolismo , Adolescente , Anti-Infecciosos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Estatura , Índice de Massa Corporal , Peso Corporal , Cromatografia Líquida de Alta Pressão , Seguimentos , Humanos , Masculino , Metronidazol/farmacocinética , Adulto JovemRESUMO
Tuberculosis (TB) is one of the most important infectious diseases, causing 1.8 million deaths annually worldwide. This problem has increased because of the association with human immmunodeficiency virus and diabetes mellitus type 2, mainly in developing countries. In the past few years it has been highlighted the significance of antimicrobial peptides in the immunopathogenesis of TB ex vivo and in experimental models studies. In this study we analyzed the expression of CAMP, DEFA1, DEFB4, and DEFB103A in patients with latent TB and progressive TB with and without comorbidity with diabetes mellitus type 2. Antimicrobial peptide gene expression increased during progressive TB, which could be used as a biomarker for reactivation. By contrast, patients with diabetes mellitus type 2 have lower antimicrobial peptides gene expression, suggesting that the lack of its proper production in these patients contribute to enhance the risk for TB reactivation.
Assuntos
Anti-Infecciosos/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/genética , Expressão Gênica , Tuberculose Latente/genética , Tuberculose/genética , Adulto , Idoso , Peptídeos Catiônicos Antimicrobianos , Catelicidinas/sangue , Catelicidinas/genética , Comorbidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Tuberculose Latente/sangue , Tuberculose Latente/epidemiologia , Tuberculose Latente/imunologia , Tuberculose Latente/patologia , Masculino , México , Pessoa de Meia-Idade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Reação em Cadeia da Polimerase , RNA Mensageiro/sangue , Tuberculose/sangue , Tuberculose/epidemiologia , Tuberculose/imunologia , Tuberculose/patologia , alfa-Defensinas/sangue , alfa-Defensinas/genética , beta-Defensinas/sangue , beta-Defensinas/genéticaRESUMO
BACKGROUND: Mycetoma is a chronic infectious disease of tropical and subtropical countries. It is produced by true fungi and actinobacteria. In México, Nocardia brasiliensis is the main causative agent of mycetoma, producing about 86% of the cases; the gold standard for the therapy of mycetoma by N. brasiliensis is the use of sulfonamides which give a 70% cure rate. The addition of amikacin to this regime increases to 95% the cure rate; however, the patients have to be monitored for creatinine clearance and audiometry studies because of the potential development of side effects. Because of that it is important to search for new active compounds. In the present work, we evaluated the in vivo effect of DA-7867, an experimental oxazolidinone, on the development of experimental mycetomas by N. brasiliensis in BALB/c mice. METHODOLOGY/PRINCIPAL FINDINGS: In order to determine the optimal dose utilized to apply to the animals, we first determined by HPLC the plasma levels using several concentrations of the compounds. Based on these results, we used 10 and 25 mg/kg subcutaneously every 24 hr; DA-7867 was also supplied in the drinking water at a calculated dose of 25 mg/kg. As a control we utilized linezolid at 25 mg/kg, a compound active in murine and human infections, three times a day. The mice were infected in the right footpad with a young culture of N. brasiliensis HUJEG-1, and one week later we started the application of the antimicrobials for six more weeks. After that we compared the development of lesions in the groups injected with saline solution or with the antimicrobials; the results were analyzed by the variance ANOVA test. DA-7867 was able to reduce the production of lesions at 25 mg/kg, when given either subcutaneously or in the drinking water. CONCLUSIONS/SIGNIFICANCE: The experimental oxazolidinone DA-7867 is active in vivo against N. brasiliensis, which opens the possibility of using this drug once it is accepted for human application. Since oxazolidinones seem to be active against a wide spectrum of actinobacteria, it is possible they could be used in human cases of mycetoma by other actinomycetales, such as Streptomyces somaliensis, highly prevalent in Sudan, or Actinomadura madurae and A. pelletieri, which are commonly observed in Africa and India.