scholarly journals Clinical Characteristics of Turkish Women withCandida kruseiVaginitis and Antifungal Susceptibility of theC. kruseiIsolates

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmet Bariş Güzel ◽  
Merve Aydın ◽  
Melda Meral ◽  
Ayşe Kalkancı ◽  
Macit Ilkit
Keyword(s):  
Clinical Characteristics ◽  
Antifungal Susceptibility ◽  
Turkish Women ◽  
Microdilution Method ◽  
Fluconazole Therapy ◽  
Dose Dependent ◽  
Susceptibility Patterns ◽  
Selection Of

Objective.Candida kruseicauses approximately 1% of vulvovaginal candidiasis (VVC) cases and is naturally resistant to fluconazole. Antifungal testing may be required ifC. kruseivaginitis fails to respond to non-fluconazole therapy, particularly in patients with recurrent infections.Design. We investigated the clinical characteristics and antifungal susceptibility profile of vaginalC. kruseiisolates. Between 2009 and 2012, we identified 560 unrelatedCandidaspp.-positive vaginal cultures, of which 28 (5.0%) wereC. krusei. These isolates were analyzed according to host factors and the clinical forms of VVC, and theirin vitrosusceptibility to 10 antifungal agents was tested using a reference microdilution method.Results. We observed that perineal laceration and increased age (>50 years) were significant predictors ofC. kruseiin vaginal samples (P<0.05). All isolates were susceptible to amphotericin B, caspofungin, ketoconazole, and miconazole. Additionally, susceptible dose-dependent and resistant rates were found for fluconazole as 42.9% and 57.1%, respectively. Remarkably, only 42.9% and 67.9% of the isolates were susceptible to itraconazole and voriconazole, respectively.Conclusions. Understanding local susceptibility patterns, especially those of non-C. albicans Candidaspecies, can significantly aid in the selection of an effective antifungal agent. Thein vivoresponse ofC. kruseivaginitis to various antifungal therapeutics remains unknown and requires further research.

Antifungal susceptibility of bloodstream yeasts isolated at a public children’s hospital in Brazil: comparison of the Etest® and the AFST–EUCAST microdilution method

2007 ◽  
Vol 53 (12) ◽  
pp. 1300-1306 ◽  
Author(s):  
Flávia E. Matsumoto ◽  
Amanda L.T. Dias ◽  
Márcia S.C. Melhem ◽  
Maria W. Szeszs ◽  
Marcos E. Auler ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Candida Spp ◽  
In Vitro Susceptibility ◽  
Microdilution Method ◽  
Susceptibility Tests ◽  
Susceptibility Profiles

This study compared the minimum inhibitory concentration (MIC) results from the proposed standard methods of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing (AFST–EUCAST) with the commercial system Etest® in the evaluation of susceptibility to flucytosine, fluconazole, itraconazole, voriconazole, and amphotericin B of 136 Candida spp. isolated from the blood of hospitalized children. The results presented a greater agreement among Etest® MICs ±2 log2 dilutions of AFST–EUCAST for fluconazole (98.1% and 96.3%) and voriconazole (100% and 100%) for Candida albicans and Candida parapsilosis . For Candida glabrata , the agreement was greater only for fluconazole (81.8%) and voriconazole (100%). For amphotericin B, the agreement between the methods was low for all species. The agreement percentage among the Etest® and AFST–EUCAST susceptibility profiles was high according to the MIC breakpoints recommended by the M27-A2 protocol for the majority of the yeasts, except for fluconazole and itraconazole against Candida tropicalis and for itraconazole against C. glabrata and Candida krusei . According to both methodologies, a great number of Candida spp. isolates showed an in vitro susceptibility to all evaluated antifungal agents. Overall, both procedures can be reliable techniques for susceptibility tests of yeasts, but the assessment of interlaboratory agreement and correlation of MICs by different methods with in vivo response are of great importance.

scholarly journals In Vitro and In Vivo Comparison of Changes in Antibiotics Susceptibility of E. coli and Chicken’s Intestinal Flora after Exposure to Amoxicillin or Thymol

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Soukayna Hriouech ◽  
Ahmed A. Akhmouch ◽  
Mariam Tanghort ◽  
Hanane Chefchaou ◽  
Aouatef Mzabi ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Intestinal Flora ◽  
Fold Increase ◽  
Resistant Bacteria ◽  
Minimal Inhibitory Concentrations ◽  
E Coli ◽  
Microdilution Method ◽  
Selection Of

This study aims at verifying, in vitro, the extent to which the use of amoxicillin or thymol induces the selection of resistant bacteria and at evaluating in vivo their effects on the development of antimicrobial resistance in the intestinal flora of poultry. E. coli strain was subcultured on agar plates containing increasing concentrations of either amoxicillin or thymol. Thereafter, minimal inhibitory concentrations (MICs) of thymol, amoxicillin, and two other antibiotics, tylosin and colistin, were determined using the microdilution method. Groups of chicks were subjected to a 2-week regime of either amoxicillin or thymol added to their drinking water. During the treatment with either thymol or amoxicillin, the total aerobic mesophilic flora (TAMF) was counted on thymol-gradient plates or amoxicillin-gradient plates and the MICs of antibiotics and thymol for E. coli isolates were determined. The in vitro test showed that for E. coli, which had been serially subcultured on increasing concentrations of amoxicillin, a 32-fold increase in MIC values for amoxicillin and a 4-fold increase for colistin and tylosin were noted. However, the MIC of thymol for this strain remained constant. For the E. coli, which had been serially subcultured on increasing concentrations of thymol, no change in the MIC values for antibiotics and thymol was observed. The in vivo test confirmed the in vitro one. It demonstrated that exposure to amoxicillin induced a selection of antimicrobial resistance in TAMF and intestinal E. coli, whereas exposure to thymol did not. The results showed that the group receiving thymol had a lower consumption index compared to the other groups. This study demonstrates the feasibility of this natural product as an alternative solution to the current use of antibiotics in poultry farming.

scholarly journals In Vitro Susceptibility ofCandidaSpecies to Four Antifungal Agents Assessed by the Reference Broth Microdilution Method

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fahriye Eksi ◽  
Efgan Dogan Gayyurhan ◽  
Iclal Balci
Keyword(s):  
Amphotericin B ◽  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Resistance Rate ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Dose Dependent

This study was performed to determine the distribution ofCandidaspecies isolated from the blood cultures of the patients hospitalized in our hospital and to investigate their antifungal susceptibility.Candidastrains were identified at species level by using classical methods and API ID 32C (bioMerieux, France) identification kits. The susceptibility of the strains to amphotericin B, fluconazole, voriconazole, and caspofungin was evaluated by using the reference broth microdilution method in document M27-A3 of the Clinical and Laboratory Standards Institute. Of the 111Candidastrains isolated, 47.7% were identified asC. albicansand 52.3% as non-albicansCandidastrains. The MIC ranges were 0.03–1 μg/mL for amphotericin B, 0.125–≥64 μg/mL for fluconazole, 0.03–16 μg/mL for voriconazole, and 0.015–0.25 μg/mL for caspofungin. AllCandidastrains were susceptible to amphotericin B and caspofungin. 10.8% isolates were resistant to fluconazole and 8.1% isolates were dose-dependent susceptible. While 0.9% isolate was resistant to voriconazole, 0.9% isolate was dose-dependent susceptible. In our study,C. albicansandC. parapsilosiswere the most frequently encountered agents of candidemia and it was detected that voriconazole with a low resistance rate might also be used with confidence in the treatment of infections occurring with these agents, primarily besides amphotericin B and caspofungin.

scholarly journals Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death

2018 ◽  
Vol 115 (32) ◽  
pp. E7469-E7477 ◽  
Author(s):  
Min Qiang ◽  
Xue Dong ◽  
Zhao Zha ◽  
Xiao-Kun Zuo ◽  
Xing-Lei Song ◽  
...  
Keyword(s):  
Ion Channels ◽  
Therapeutic Agents ◽  
Natural State ◽  
Proof Of Concept ◽  
Acid Sensing Ion Channels ◽  
Functional Antibodies ◽  
Dose Dependent ◽  
Selection Of

Acid-sensing ion channels (ASICs) have emerged as important, albeit challenging therapeutic targets for pain, stroke, etc. One approach to developing therapeutic agents could involve the generation of functional antibodies against these channels. To select such antibodies, we used channels assembled in nanodiscs, such that the target ASIC1a has a configuration as close as possible to its natural state in the plasma membrane. This methodology allowed selection of functional antibodies that inhibit acid-induced opening of the channel in a dose-dependent way. In addition to regulation of pH, these antibodies block the transport of cations, including calcium, thereby preventing acid-induced cell death in vitro and in vivo. As proof of concept for the use of these antibodies to modulate ion channels in vivo, we showed that they potently protect brain cells from death after an ischemic stroke. Thus, the methodology described here should be general, thereby allowing selection of antibodies to other important ASICs, such as those involved in pain, neurodegeneration, and other conditions.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Vasorelaxant and Antihypertensive Effects of Mentha pulegium L. in Rats: An in vitro and in vivo Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Mohammed Ajebli ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Acute Experiment ◽  
Antihypertensive Activity ◽  
Mentha Pulegium ◽  
In Vitro Experiment ◽  
Arterial Blood ◽  
Dose Dependent ◽  
Ca2 Channels

Aims and objective: The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in Morocco. Material and methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats have received orally MPAE (180 and 300 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. While, in the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to dilation of blood vessels via blockage of Ca2+ channels.

scholarly journals 146. antifungal Susceptibility Patterns of candida Parapsilosis Bloodstream Isolates in the US, 2008–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S203-S203
Author(s):  
Brenda L Tesini ◽  
Meghan Lyman ◽  
Brendan R Jackson ◽  
Anita Gellert ◽  
William Schaffner ◽  
...  
Keyword(s):  
Candida Species ◽  
Regional Variation ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Emerging Infections ◽  
In Vitro Susceptibility ◽  
Fluconazole Resistance ◽  
The Us ◽  
Susceptibility Patterns

Abstract Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (&lt; 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

scholarly journals In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Merricka C. Livingstone ◽  
Alexis A. Bitzer ◽  
Alish Giri ◽  
Kun Luo ◽  
Rajeshwer S. Sankhala ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Monoclonal Antibodies ◽  
Disease Burden ◽  
Vaccine Candidate ◽  
Specific Binding ◽  
Circumsporozoite Protein ◽  
Target Epitope ◽  
Selection Of

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xuxing Shen ◽  
Chao Wu ◽  
Meng Lei ◽  
Qing Yan ◽  
Haoyang Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Serum Enzyme ◽  
Herg Channels ◽  
Anti Tumor Activity ◽  
Dose Dependent

AbstractCarfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.

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