RESUMO
Severe acute respiratory syndrome (SARS) is a life-threatening disease for which accurate diagnosis is essential. Although many tools have been developed for the diagnosis of SARS, false-positive reactions in negative sera may occur because of cross-reactivity with other coronaviruses. We have raised polyclonal and monoclonal antibodies (Abs) using a recombinant form of the SARS virus nucleocapsid protein. Cross-reactivity of these anti-SARS Abs against human coronavirus (HCoV) 229E and HCoV OC43 were determined by Western blotting. The Abs produced reacted with recombinant SARS virus nucleocapsid protein, but not with HCoV 229E or HCoV OC43.
Assuntos
Humanos , Anticorpos Antivirais/imunologia , Western Blotting , Coronavirus Humano 229E/imunologia , Coronavirus Humano OC43/imunologia , Reações Cruzadas , Proteínas do Nucleocapsídeo/genética , Proteínas Recombinantes/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/diagnósticoRESUMO
Whereas endogenous estrogens play an important role in the development, maintenance, and function of female and male reproductive organs, xenoestrogens present in the environment disrupt normal endocrine function in humans and wildlife. Various in vivo and in vitro assays have been developed to screen these xenoestrogens. However, traditional in vivo assays are laborious and unsuitable for large-scale screening, and in vitro assays do not necessarily replicate in vivo functioning. To overcome these limitations, we developed a transient expression assay in zebrafish, into which a brain aromatase (cyp19a1b)-based estrogen-responsive reporter gene was introduced. In response to 17beta-estradiol (10(-6) M) and heptachlor (10(-6) M), zebrafish embryos carrying the reporter construct expressed enhanced green fluorescent protein in the olfactory bulb, telencephalon, preoptic area, and mediobasal hypothalamus. This system will serve to model the in vivo conversion and breakdown of estrogenic compounds and thus provide a rapid preliminary screening method to estimate their estrogenicity.
Assuntos
Aromatase/genética , Bioensaio , Encéfalo/enzimologia , Receptores de Estrogênio/metabolismo , Proteínas de Peixe-Zebra/genética , Peixe-Zebra , Animais , Aromatase/metabolismo , Encéfalo/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/enzimologia , Disruptores Endócrinos/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Heptacloro/farmacologia , Inseticidas/farmacologia , Masculino , RNA Mensageiro/metabolismo , Receptores de Estrogênio/efeitos dos fármacos , Transfecção , Proteínas de Peixe-Zebra/metabolismoRESUMO
Genistein is a phytoestrogen found at a high level in soybeans. In vitro and in vivo studies showed that high concentrations of genistein caused toxic effects. This study was designed to test the feasibility of zebrafish embryos for evaluating developmental toxicity and estrogenic potential of high genistein concentrations. The zebrafish embryos at 24 h post-fertilization were exposed to genistein (1 x 10(-4) M, 0.5 x 10(-4) M, 0.25 x 10(-4) M) or vehicle (ethanol, 0.1%) for 60 h. Genistein-treated embryos showed decreased heart rates, retarded hatching times, decreased body length, and increased mortality in a dose-dependent manner. After 0.25 x 10(-4) M genistein treatment, malformations of survived embryos such as pericardial edema, yolk sac edema, and spinal kyphosis were also observed. TUNEL assay results showed apoptotic DNA fragments in brain. This study also confirmed the estrogenic potential of genistein by EGFP expression in the brain of the mosaic reporter zebrafish embryos. This study first demonstrated that high concentrations of genistein caused a teratogenic effect on zebrafish embryos and confirmed the estrogenic potential of genistein in mosaic reporter zebrafish embryos.
Assuntos
Aromatase/biossíntese , Encéfalo/efeitos dos fármacos , Genisteína/toxicidade , Teratogênicos/toxicidade , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Encéfalo/embriologia , Encéfalo/enzimologia , Primers do DNA , Relação Dose-Resposta a Droga , Indução Enzimática , Genes Reporter , Marcação In Situ das Extremidades Cortadas , Testes de ToxicidadeRESUMO
The effect of NaCl plus 3% chitosan on the systolic blood pressure of spontaneously hypertensive rats (SHR) were evaluated and compared with NaCl plus KCl (NaCl, 49.36% + KCl 49.36%) and chitosan or NaCl treatment alone. In SHR, administration of NaCl plus chitosan (44 mM Na/day) for two months significantly decreased the systolic blood pressure greater than of NaCl plus KCl and NaCl alone. NaCl plus chitosan resulted, though not statistically significant, in decreased urinary Na(+) excretion and decreased blood urea nitrogen levels. Urinary creatinine of NaCl plus chitosan was slightly decreased compared to 3 treated groups. Serum electrolytes levels, however, remained unchanged. The combination of NaCl and chitosan may be superior to the conventional use of NaCl plus KCl or NaCl alone in the prevention of hypertension. Even though these supplementary diets have demonstrated potential anti-hypertensive effects in the experimental animal model, further research is needed before any recommendations can be made.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Quitosana/administração & dosagem , Hipertensão/prevenção & controle , Cloreto de Sódio na Dieta/administração & dosagem , Angiotensina I/sangue , Angiotensina II/biossíntese , Animais , Pressão Sanguínea/fisiologia , Nitrogênio da Ureia Sanguínea , Peso Corporal/efeitos dos fármacos , Cloretos/sangue , Cloretos/urina , Creatinina/urina , Coração/fisiologia , Histocitoquímica , Rim/fisiologia , Masculino , Potássio/sangue , Potássio/urina , Cloreto de Potássio/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Sódio/sangue , Sódio/urina , Sístole/efeitos dos fármacos , Sístole/fisiologiaRESUMO
Benomyl is a benzimidazole fungicide that has been widely used on a variety of food crops and ornamental plants. It is known to cause adverse effects on reproductive systems, including decreased testicular and epididymal weights and reduced epididymal sperm counts and fertility. The brain aromatase gene is up-regulated by estrogens and estrogen mimics and considered a target gene to screen estrogen mimics. This study was designed to test the estrogenic potential and toxic effects of benomyl in the zebrafish system, and validated this system as a model that may correspond to the effect of benomyl in rodents. Concentrations of 20 x 10(-6), 40 x 10(-6) and 80 x 10(-6) M of benomyl-treated embryos showed decreased survival, hatching and heart rates, and increased incidence of malformations, such as pericardial edema, spinal lordosis, elongated heart, head edema, eye lens protrusion and caudal fin disappearance. Benomyl induced enhanced green fluorescent protein (EGFP) expression in the mediobasal hypothalamus (MBH) in transient zebrafish embryos with a brain aromatase-based reporter gene. In this study, we determined that benomyl has estrogenic potential based on zebrafish brain aromatase gene induction, and that benomyl is toxic at 20 x 10(-6) M concentration and higher. These results demonstrate the usefulness of zebrafish embryos as an in vivo system to examine the estrogenic and developmental toxic potential of unknown compounds.
Assuntos
Aromatase/biossíntese , Benomilo/toxicidade , Encéfalo/enzimologia , Embrião não Mamífero/fisiologia , Fungicidas Industriais/toxicidade , Peixe-Zebra/fisiologia , Animais , Aromatase/genética , Encéfalo/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Frequência Cardíaca/efeitos dos fármacos , Microinjeções , Plasmídeos/genética , Análise de Sobrevida , Teratogênicos/toxicidade , Transposases/biossíntese , Transposases/genéticaRESUMO
Severe acute respiratory syndrome (SARS) is a lifethreatening emerging respiratory disease caused by the coronavirus, SARS-CoV. The nucleocapsid (N) protein of SARS-CoV is highly antigenic and may be a suitable candidate for diagnostic applications. We constructed truncated recombinant N proteins (N1 [1-422 aa], N2 [1- 109 aa], and N3 [110-422 aa]) and determined their antigenicity by Western blotting using convalescent SARS serum. The recombinants containing N1 and N3 reacted with convalescent SARS serum in Western blotting. However, the recombinant with N2 did not. In ELISA using N1 or N3 as the antigens, positive results were observed in 10 of 10 (100%) SARS-CoV-positive human sera. None of 50 healthy sera gave positive results in either assay. These data indicate that the ELISA using N1 or N3 has high sensitivity and specificity. These results suggest that the middle or C-terminal region of the SARS N protein is important for eliciting antibodies against SARS-CoV during the immune response, and ELISA reactions using N1 or N3 may be a valuable tool for SARS diagnosis.
Assuntos
Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Nucleocapsídeo/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Antígenos Virais/imunologia , Antígenos Virais/isolamento & purificação , Antígenos Virais/metabolismo , Expressão Gênica , Humanos , Nucleocapsídeo/isolamento & purificação , Nucleocapsídeo/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Síndrome Respiratória Aguda Grave/diagnósticoRESUMO
It is believed today that nucleocapsid protein (N) of severe acute respiratory syndrome (SARS)-CoV is one of the most promising antigen candidates for vaccine design. In this study, three fragments [N1 (residues: 1-422); N2 (residues: 1-109); N3 (residues: 110-422)] of N protein of SARS-CoV were expressed in Escherichia coli and analyzed by pooled sera of convalescence phase of SARS patients. Three gene fragments [N1 (1-1269 nt), N2 (1-327 nt) and N3 (328-1269 nt)-expressing the same proteins of N1, N2 and N3, respectively] of SARS-N were cloned into pVAX-1 and used to immunize BALB/c mice by electroporation. Humoral (by enzyme-linked immunosorbent assay, ELISA) and cellular (by cell proliferation and CD4(+):CD8(+) assay) immunity was detected by using recombinant N1 and N3 specific antigen. Results showed that N1 and N3 fragments of N protein expressed by E. coli were able to react with sera of SARS patients but N2 could not. Specific humoral and cellular immunity in mice could be induced significantly by inoculating SARS-CoV N1 and N3 DNA vaccine. In addition, the immune response levels in N3 were significantly higher for antibody responses (IgG and IgG1 but not IgG2a) and cell proliferation but not in CD4(+):CD8(+) assay compared to N1 vaccine. The identification of antigenic N protein fragments has implications to provide basic information for the design of DNA vaccine against SARS-CoV. The present results not only suggest that DNA immunization with pVax-N3 could be used as potential DNA vaccination approaches to induce antibody in BALB/c mice, but also illustrates that gene immunization with these SARS DNA vaccines can generate different immune responses.
Assuntos
Epitopos/imunologia , Nucleocapsídeo/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos/imunologia , Linhagem Celular , Proliferação de Células , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nucleocapsídeo/genética , Nucleocapsídeo/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Vacinas de DNA/genética , Vacinas de DNA/metabolismo , Vacinas Virais/genética , Vacinas Virais/metabolismoRESUMO
The cardiovascular drug lacidipine was screened in vitro for possible antibacterial activity with respect to 389 Gram-positive and Gram-negative bacterial strains. It was noticed that most bacteria (233) failed to grow at 50-200 microg/mL concentrations of the drug. Some strains were inhibited at even lower concentrations. The bacteria could be arranged according to their decreasing order of sensitivity as follows: Staphylococcus aureus, Vibrio cholerae, Salmonella spp., Shigellae, Escherichia coli, Bacillus spp., Klebsiellae and Pseudomonas spp. Lacidipine was found to be bacteriostatic in nature against S. aureus and V cholerae. When administered to Swiss strain of white mice at doses of 30 and 60 microg/mouse, lacidipine significantly protected the animals challenged with 50 MLD of S. typhimurium NCTC 74. According to the chi-square test, the in vivo data were highly significant (p<0.001).
Assuntos
Antibacterianos/farmacologia , Fármacos Cardiovasculares/farmacologia , Di-Hidropiridinas/farmacologia , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/uso terapêutico , Di-Hidropiridinas/química , Di-Hidropiridinas/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Camundongos , Estrutura Molecular , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Testes de ToxicidadeRESUMO
Diclofenac sodium (Dc), an anti-inflammatory agent, has remarkable inhibitory action both against drug-sensitive and drug-resistant clinical isolates of various Gram-positive and Gram-negative bacteria. The aim of this study was to determine the ability of Dc to protect mice from a virulent Salmonella infection. Dc injected at 1.5 microg/g and 3.0 microg/g mouse body weight significantly protected animals from the lethality of Salmonella infection. As was the case for the in vitro interaction, Dc in combination with streptomycin was even more effective. The non-antibiotic drug Dc has potential for the management of problematic antibiotic-resistant bacterial infections.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Diclofenaco/uso terapêutico , Farmacorresistência Bacteriana , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Antipsicóticos/farmacologia , Contagem de Colônia Microbiana , Meios de Cultura , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Diclofenaco/toxicidade , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Salmonella enterica/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Estreptomicina/farmacologia , Trifluoperazina/farmacologiaRESUMO
The non-steroidal anti-inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo antimycobacterial activity. The aim of this study was to ascertain whether DCL used in combination with the first-line antitubercular antibiotic streptomycin (STM) synergistically augments its efficacy in vitro as well as in a murine tuberculosis infection model. In vitro minimum inhibitory concentrations (MICs) and synergistic activities of the drugs with respect to standard strains and clinical isolates of Mycobacterium tuberculosis were determined. Swiss albino male mice were intravenously infected with 2.3x10(7) M. tuberculosis H37Rv. Mice were treated with DCL or STM alone as well as in combination for 4 weeks to determine the survival rate, spleen weight and colony-forming unit (CFU) counts in the lungs and spleen. DCL was bactericidal at 40 microg/mL (4xMIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 microg/g/day DCL or 150 microg/g/day STM for 4 weeks, administered from 1 day post infection, significantly (P<0.05) lowered bacterial counts and reduced mean spleen weight of mice compared with untreated animals. Simultaneous administration of both agents further decreased CFU counts (P<0.05) in the lungs and spleen compared with mice receiving STM alone. Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in murine tuberculosis, and further investigations may throw light on new directions to combat multidrug-resistant tuberculosis infections in humans.
Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Estreptomicina/uso terapêutico , Tuberculose/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Diclofenaco/administração & dosagem , Diclofenaco/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Pulmão/microbiologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Baço/microbiologia , Baço/patologia , Estreptomicina/administração & dosagem , Estreptomicina/farmacologia , Análise de SobrevidaRESUMO
E. coli is the main agent of uncomplicated urinary tract infections (UTIs) and accounts for more than 85% of recurrent cystitis and at least 35% of recurrent pyelonephritis. Despite the widespread availability of antibiotics, UTIs remain the most common bacterial infection in the human population. It is currently advised that the clinical administration of antibiotics against the pathogenic bacteria should be prohibitted due to the emergence of multidrug resistant (MDR) bacterial strains. Therefore, newer and more effective antimicrobials are in demand to treat such cases. One hundred and thirty six urine samples were collected from UTI patients. E. coli was isolated from 85 samples, out of which 33% were resistant to common antibiotics. The isolates were decreasingly resistant to ampicillin, tobramycin, augmentin, nalidixic acid, cefuroxime, nitrofurantoin, kanamycin, pipemidic acid, chloramphenicol, cefotaxime, cefamendol, ofloxacin, ceftizoxime, norfloxacin and amikacin. The anti-inflammatory drug diclofenac exhibited significant antibacterial activity against common bacterial strains both in vitro and in vivo. The present work was conducted to evaluate the in vitro inhibitory effect of this drug on the clinically isolated strains of E. coli in hospitals. All the isolates were sensitive to diclofenac, with MIC values ranging from 5-50 microg/mL. The MIC90 value of the drug was 25 microg/mL. Therefore, it may be suggested that diclofenac has the capacity to treat UTI caused by E. coli.
Assuntos
Antibacterianos/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Diclofenaco/uso terapêutico , Infecções por Escherichia coli/terapia , Infecções Urinárias/tratamento farmacológico , Animais , Inibidores de Ciclo-Oxigenase/farmacocinética , Diclofenaco/química , Diclofenaco/farmacocinética , Farmacorresistência Bacteriana , Escherichia coli/genética , Infecções por Escherichia coli/urina , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
Thepiperazine chlorcyclizine HCl (CCZ), possessing significant antimetabolic as well as virucidal and virustatic activities against the human immunodeficiency virus (HIV) and other retroviruses, was selected to determine its anticarcinogenic potential The anticancer activity of CCZ was evaluated against procarcinogen n-diethylnitrosamine (NDA)-initiated hepatocarcinogenesis, which was subsequently promoted by phenobarbital (PB) in male Sprague-Dawley rats. The anticancer efficacy of CCZ was monitored by estimating some potential markers of neoplastic and preneoplastic hepatic conditions, e.g., glutathione (GSH), glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase (gammaGTP). CCZ exhibited antineoplastic activity on a long-term therapeutic basis. Furthermore, this drug restricted the exponential increase of the antioxidant markers in the hyperplastic nodule and the surrounding liver tissues in comparison with the carcinogen-controlled rats during the entire period of treatment. A decrease in the number of nodules was observed in the CCZ-treated group.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Piperazinas/uso terapêutico , Animais , Carcinógenos/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/toxicidade , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Fenobarbital/toxicidade , Ratos , Ratos Sprague-DawleyRESUMO
The antipsychotic thioxanthene flupenthixol, possessing a trifluoromethyl substituent at position 2, exhibited a distinct antibacterial property against 352 strains of bacteria from 3 Gram-positive and 13 Gram-negative genera. The minimum inhibitory concentration (MIC) of flupenthixol was determined by the National Committee for Clinical Laboratory Standards agar dilution method. MICs ranged from 10-100 microg/mL in most of the strains, whilst some strains were inhibited at even lower concentrations. The mode of action of this drug was found to be bacteriostatic against Staphylococcus aureus and Vibrio cholerae. In the in vivo experiments, this drug was capable of contributing significant protection (P < 0.001) to a Swiss strain of white mice challenged with 50 median lethal dose of a mouse-virulent strain at a drug concentration of 15 microg/mouse. In addition, flupenthixol remarkably reduced the number of viable bacteria in organ homogenates and blood of mice treated with this drug.
Assuntos
Antibacterianos/farmacologia , Flupentixol/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Flupentixol/química , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Salmonelose Animal/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Vibrio cholerae/efeitos dos fármacosRESUMO
Methyl-L-DOPA, an antihypertensive agent, has significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. xenopi and M. marinum, and rare pathogens like M. fortuitum. In the present investigation, the screening of the in vitro activity was further extended by testing the in vitro activity against a total of 53 different strains of mycobacteria, including 34 clinical isolates of both drug-sensitive and drug-resistant Mycobacterium tuberculosis. Most of the strains were inhibited at 10-25 microg/mL concentrations of the drug. When methyl-L-DOPA was injected into male mice at a concentration of 10 microg/g body weight (20 g each), methyl-L-DOPA significantly protected them when challenged with a 50 median lethal dose of M. tuberculosis H37Rv102. According to the chi2 test, the in vivo data were highly significant (p<0.01).
Assuntos
Antibacterianos/farmacologia , Anti-Hipertensivos/farmacologia , Levodopa/análogos & derivados , Mycobacterium/efeitos dos fármacos , Animais , Farmacorresistência Bacteriana , Resistência a Múltiplos Medicamentos , Humanos , Levodopa/farmacologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium/classificação , Mycobacterium/isolamento & purificação , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológicoRESUMO
The cardiovascular drug oxyfedrine HCl revealed noteworthy in vitro antibacterial action against 501 strains of Gram positive and Gram negative bacteria. It also offered significant protection to mice challenged with a mouse-virulent bacterial strain. Prompted by such results, the present study was carried out to ascertain whether this drug could augment the efficiency of an antibiotic when used in combination with it. For this purpose, ten bacterial strains were selected, which were sensitive to oxyfedrine as well as to six antibiotics, like benzyl penicillin, chloramphenicol, ciprofloxacin, erythromycin, streptomycin and tetracycline. Distinct and statistically significant (p<0.01) synergism was observed between oxyfedrine and tetracycline by disc diffusion tests, compared with their individual effects. The fractional inhibitory concentration (FIC) index of this combination, evaluated by checkerboard analysis, was 0.37, which confirmed synergism between the pair. This synergistic drug duo was further dispensed to infected mice. The results of the mouse-protection tests advocated that the combination was significantly synergistic (p<0.0001), according to Student's 't' test. Hence, the capacity of extended antibiotic therapy in several microbial diseases may be improved with the help of this synergistic drug pair, and the study might throw light on newer directions to contest drug-resistant bacterial infections.
Assuntos
Antibacterianos/farmacologia , Oxifedrina/farmacologia , Tetraciclina/farmacologia , Animais , Bactérias/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Salmonelose Animal/tratamento farmacológico , Salmonella typhimurium/efeitos dos fármacosRESUMO
The antipsychotic drug prochlorperazine was screened in vitro for possible antimicrobial property against 157 strains of bacteria, belonging to gram positive and gram negative genera. The minimum inhibitory concentration (MIC) of prochlorperazine was determined by agar dilution method, which ranged from 25 to 200 microg/ml with respect to most of the strains. Based on such findings, a further study was undertaken to determine whether the efficacy of this drug could be enhanced in the presence of an antihistaminic agent methdilazine, reported to have remarkable antimicrobial action. Four bacterial strains, sensitive to prochlorperazine as well as to three antibacterial chemotherapeutics, viz., methdilazine, fluphenazine and thioridazine were chosen. Disc diffusion tests with prochlorperazine and methdilazine revealed marked synergism between the combination, compared to their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergism, the checkerboard analysis was performed. The FIC index of this combination turned out to be 0.37, which confirmed synergism. Therefore, this synergistic drug combination might open a new therapeutic approach to combat drug-resistance in bacterial infections.
Assuntos
Antipsicóticos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Fenotiazinas/farmacologia , Proclorperazina/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Amlodipine, a cardiovascular drug, exhibited remarkable antibacterial action in vitro against 504 bacterial strains belonging to both Gram positive and Gram negative genera, as well as in vivo against a mouse-virulent bacterium. Based on such findings, the present study was undertaken to determine whether the efficacy of this non-antibiotic drug could be enhanced in the presence of any antibiotic. Twelve bacterial strains, sensitive to amlodipine as well as to 6 antibiotics, viz., benzyl penicillin, streptomycin, chloramphenicol, tetracycline, erythromycin and ciprofloxacin were chosen. Disc diffusion test with amlodipine and streptomycin revealed marked synergism between the combination, compared with their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergy, the checkerboard analysis was performed. The fractional inhibitory concentration (FIC) index of this combination turned out to be 0.24, which confirmed synergism. This antibiotic-non-antibiotic pair was then administered to mice, challenged with S. typhimurium to determine whether this was effective in vivo. Statistical analysis of the mouse protection tests suggested that the combination was highly synergistic (p<0.001), according to Student's t-test. This synergistic drug combination may help us in enhancing the scope of prolonged antibiotic therapy in various types of infections, and might open a new therapeutic approach to combat drug resistance in bacterial diseases.