scholarly journals In vitro synergistic effect of baicalin with azithromycin against Staphylococcus saprophyticus isolated from francolins with ophthalmia

2019 ◽  
Vol 98 (1) ◽  
pp. 373-380 ◽  
Author(s):  
Jinli Wang ◽  
Mingyu Qiao ◽  
Yefeng Zhou ◽  
Hongxu Du ◽  
Jingying Bai ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Staphylococcus Saprophyticus

Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin’s Lymphoma Cells through NF-κB Inhibition and are Synergistic with Doxorubicin and Etoposide

2020 ◽  
Vol 20 (6) ◽  
pp. 715-723
Author(s):  
Natarajan Nandakumar ◽  
Pushparathinam Gopinath ◽  
Jacob Gopas ◽  
Kannoth M. Muraleedharan
Keyword(s):  
Synergistic Effect ◽  
Hodgkin’S Lymphoma ◽  
A549 Cells ◽  
Hodgkin's Lymphoma ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Lymphoma Cells ◽  
Nuclear Extracts ◽  
Gene Assay

Background: The authors investigated the NF-κB inhibitory role of three Benzisothiazolone (BIT) derivatives (1, 2 and 3) in Hodgkin’s Lymphoma cells (L428) which constitutively express activated NF-κB. All three compounds showed dose-dependent NF-κB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter gene assay and were found cytotoxic at IC50 values of 3.3μg/ml, 4.35μg/ml and 13.8μg/ml, respectively by the XTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-κB subunits p50 and p65 in cytoplasmic and nuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect with the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate additive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under various concentrations, except in the case of 1.56μg/ml of BIT 3 with 0.156μg/ml of cisplatin. The compounds also inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further investigated for future potential therapeutic use. Methods: Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones were synthesized from dithiodibenzoic acid and their NF-κB inhibitory role was explored. NF-κB inhibition and cytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay. Immunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the A549 cell line. L428 cells were used to conduct combination studies and the results were plotted using CompuSyn software. Results: Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. Potent compounds showed suppression of both NF-κB subunits p50 and p65 in a concentrationdependent manner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone derivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds also inhibited the migration of A549 cells. Conclusion: Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic framework exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. In addition, these derivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the migration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer agents.

scholarly journals In VitroSynergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nishanth Kumar Sasidharan ◽  
Sreerag Ravikumar Sreekala ◽  
Jubi Jacob ◽  
Bala Nambisan
Keyword(s):  
Synergistic Effect ◽  
New Combination ◽  
Normal Fibroblast ◽  
Infectious Diarrhea ◽  
Combination Drug ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
Third Generation Cephalosporins

Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 μg/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria inin vitrocondition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria.

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

2014 ◽  
Vol 306 (2) ◽  
pp. L207-L215 ◽  
Author(s):  
Masahiro Enomoto ◽  
Amish Jain ◽  
Jingyi Pan ◽  
Yulia Shifrin ◽  
Todd Van Vliet ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Synergistic Effect ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Small Heat Shock Protein ◽  
No Donor ◽  
Clinical Exposure ◽  
Pulmonary Vasodilators ◽  
Pulmonary Vasodilator

Inhaled nitric oxide (NO) and other cGMP- or cAMP-dependent pulmonary vasodilators are often used in combination for the treatment of the persistent pulmonary hypertension of the newborn syndrome. There is in vitro evidence to indicate that NO downregulate the pulmonary vascular response to cGMP-dependent agonists raising concern as to whether a synergistic effect is observed when employing a combined strategy in newborns. Hypothesizing that a synergistic effect is absent, we evaluated newborn and juvenile rat pulmonary arteries to determine the individual and combined vasodilatory effect of cGMP- and cAMP-dependent agonists. In precontracted near-resistance pulmonary arteries, the addition of sildenafil reduced vasorelaxation response to NO donor S-nitroso- N-acetyl penicillamine (SNAP). A similar decrease in SNAP-induced vasodilation was observed in arteries pretreated with BAY 41–2272 (10−9 M), a soluble guanylate cyclase stimulator cGMP, and its downstream protein kinase activator. cGMP also reduced the vasorelaxant response to the cAMP-dependent forskolin. Inhibition of endogenous vascular NO generation enhanced SNAP-induced relaxation. The present data suggest that the mechanism involved in the cGMP desensitization to other relaxant agonists involves downregulation of the small heat shock protein HSP20 and is evident in rat pulmonary and systemic vascular smooth muscle cells. In newborn rats with chronic hypoxia-induced pulmonary hypertension, the combination of sildenafil and inhaled NO resulted in a lesser reduction in pulmonary vascular resistance compared with their individual effect. These data suggest that clinical exposure to one cGMP-dependent pulmonary vasodilator may affect the response to other cGMP- or cAMP-mediated agonists.

CURRENT STATUS OF COMBINED ANTIBIOTIC THERAPY

PEDIATRICS ◽  
1958 ◽  
Vol 21 (6) ◽  
pp. 1000-1009
Author(s):  
Charles V. Pryles
Keyword(s):  
Synergistic Effect ◽  
Bacterial Resistance ◽  
Current Status ◽  
Causative Organism ◽  
In Vitro Tests ◽  
Aminosalicylic Acid ◽  
Tract Infections ◽  
Vitro Effect ◽  
Group 1

The use of combinations of drugs in "shotgun" fashion, on the theory if one will do something, two or three will accomplish more, is to be deplored. A single antibiotic can be used effectively in most infections caused by a single organism. Furthermore, a single wide-spectrum antibiotic may be used in many mixed infections. In certain infections, the value of combinations of antibiotics has been proved, both in the laboratory and in the clinic: (a) streptomycin plus one of the tetracyclines in brucellosis; (b) penicillin plus streptomycin in enterococcic endocarditis; (c) erythromycin plus chloramphenicol in serious staphylococcal infections in which the organism is resistant to penicillin; (d) streptomycin, isoniazid and para-aminosalicyclic acid in treatment of tuberculosis. In these infections, the proper combination should be used from the start and in full therapeutic dosage. Mixtures of antibiotics may occasionally be useful in individual cases outside this group but, in general, these mixtures do not produce a synergistic effect. If the infection does not fall into one of the four classes already cited, the in-vitro effect of combinations of various antibiotics should be studied, providing the patient's illness is such that a delay of 48 to 72 hours is warranted. The combination showing the greatest synergistic effect should then be used. Persisting urinary tract infections and endocarditis are examples of conditions in which this method is likely to produce results. Even here, it must be borne in mind that such in-vitro tests do not guarantee that a certain mixture of antibiotics will be effective clinically; in fact, they may be misleading. In accord with the recommendations of Dowling, if there is not sufficient time for an in-vitro study to be carried out, two antibiotics in Jawetz and Gunnison's Group 1 (see text) may be used together, if each alone is partially effective against the causative organism. If no two antibiotics in Group 1 fit this criterion, and a combination of an antibiotic from Group 1 and one from Group 2 does fit the criterion, this combination should be given in doses that will result in full therapeutic concentrations of each antibiotic at the site of infection. For delaying the emergence of resistant strains of tubercle bacilli, combinations of two or more of the following drugs are indicated: Streptomycin, isoniazid and para-aminosalicylic acid. A combination of chloramphenicol with erythromycin is also indicated to delay emergence of resistance of staphylococci to the batter antibiotics. In the treatment of seriously ill patients before a bacteriologic diagnosis is available, two or more antibiotics may properly be administered. Such illnesses include endocarditis, suspected staphylococcal pneumonia in infants, tuberculosis, brucellosis, and meningitis due to an unidentified organism. Combined antimicrobials should be given only after a careful clinical diagnosis has been made, and in doses that would be optimal for each drug if used alone. Readymade mixtures are not recommended for use systemically; certain combinations of agents, such as a mixture of bacitracin and polymyxin B, may have a place in topical therapy. Finally, there are several potentially harmful or undesirable effects that may result from the use of combinations of antimicrobials and these must be considered whenever their possible use arises. These include: (1) the tendency of fixed, "packaged" combinations to encourage inadequate therapy; (2) the possible increase in hypersensitivity and/or toxicity to one or more of the agents in a combination; (3) the probable emergence of bacterial resistance to either or both of the antibiotics in a mixture; (4) superinfection by originally resistant organisms not affected by the therapy; (5) the accumulation of antibiotic-resistant organisms within hospitals or other semiclosed communities; and (6) the possibility of interference of one antibiotic with the operation of another in a given combination.

In Vitro Synergistic Effect of Minocycline Combined with Antifungals against Cryptococcus Neoformans

2021 ◽  
pp. 101227
Author(s):  
Lihua Tan ◽  
Haiyan Shi ◽  
Mei Chen ◽  
Zikuo Wang ◽  
Zhaoqian Yao ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Cryptococcus Neoformans
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