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Rabbit Model of Candida albicans Biofilm Infection: Liposomal Amphotericin B Antifungal Lock Therapy

Research Abstract
Catheter-related infections due to Candida albicans biofilms are a leading cause of fungal nosocomial bloodstream infection. In this paper, we describe the development of a model of catheter-associated infection with C. albicans biofilms and show that antifungal lock therapy with liposomal amphotericin B is an effective treatment strategy for these infections. Silicone catheters surgically placed in New Zealand White rabbits were infected with C. albicans, and the rabbits were randomized into three groups: (i) untreated controls, (ii) liposomal amphotericin B lock, and (iii) fluconazole lock. Upon completion of therapy, blood cultures were obtained and the catheters were removed for quantitative culture and scanning electron microscopic analyses. Quantitative cultures revealed that catheters treated with liposomal amphotericin B yielded 0 CFU, which was significant compared to the untreated controls (P < 0.001) and the fluconazole-treated group (P = 0.0079). Although fluconazole treatment tended to have lower CFU compared to untreated controls, there was no difference in mean colony counts between these two groups (1.128 ± 0.764 and 1.841 ± 1.141 log10 CFU/catheter segment, respectively; P = 0.297). Scanning electron microscopy revealed abundant biofilm in the control and fluconazole groups, while the liposomal amphotericin B group was virtually cleared. These findings suggest a possible treatment strategy for the successful salvage of catheters infected with C. albicans biofilms and describe an animal model that may play an important role in the further study of C. albicans biofilm pathogenesis and evaluation of potential antibiofilm agents.
Nosocomial bloodstream infections are a significant cause of morbidity and mortality among hospitalized patients, with Candida species representing the fourth most common cause of such infections (9). Central venous catheters (CVCs) are responsible for many of these infections, and up to 40% of patients with Candida isolated from their CVCs have underlying fungemia (1). Despite the introduction of new antifungal therapies, the attributable mortality of patients with candidemia remains unacceptably high, ranging from 39 to 49% (10, 26).
Adherence of microorganisms and biofilm formation on catheter surfaces is a common mechanism for catheter-associated bloodstream infection (20). These biofilms are characterized by the production of a thick extracellular matrix and an altered resistance phenotype (8). Electron microscopic evaluation of catheters removed from patients has demonstrated widespread biofilm colonization, confirming the importance of biofilms in catheter-associated infections (20). CVCs infected with Candida biofilms are especially problematic since Candida species adhere avidly to catheter material and antifungal therapy alone is insufficient for cure (6). This explains the rationale behind the recent national guidelines recommending the removal of catheters infected with Candida in order to eradicate a potential nidus of bloodstream infection (17, 19). However, catheter removal is not always feasible for patients with coagulopathy or limited vascular access and is associated with increased healthcare expenses as well as complications related to catheter replacement (18).
Data from several laboratories have demonstrated the near-total resistance of in vitro Candida albicans biofilms to common antifungal agents (6, 7, 13, 15). More recently, our group and others have observed that in vitro C. albicans biofilms show susceptibility to the lipid formulations of amphotericin B and the echinocandins (3, 16). Although these data suggest a possible strategy for the salvage of CVCs infected with C. albicans biofilms, the clinical significance of these observations remains unknown. There has been no in vivo validation of these findings because (i) no animal model of catheter-related C. albicans biofilm infection is available and (ii) no prospective, randomized clinical trials have been performed. In this study, we describe the development of the first clinically relevant animal model of C. albicans biofilm-associated catheter infection and evaluate the effectiveness of liposomal amphotericin B antifungal lock therapy.
Research Authors
Matthew K. Schinabeck, Lisa A. Long, Mohammad A. Hossain, Jyotsna Chandra, Pranab K. Mukherjee, Sotohy Mohamed, Mahmoud A. Ghannoum
Research Date
Research Department
Research Member

Effect of aqueous extract of Miswak ( Salvadora persica) on histomorphological structure of the uterus in the female rats

Research Abstract

uterus is a very important reproductive organ for implantation and holding embryos till labor. Many drugs and medicinal plants affect the uterus, some researchers reported that Salvadora persica (Miswak) is a phytoestrogen plant as it contains flavonoids and can be used as a contraceptive drug; however, no available investigations explain the histomorphological structure of the uterus after Miswak extract administration. Twelve female albino rats (165.3 ± 3.269 g) were divided equally into two groups.  In the control group, the animals received normal saline daily for 4 weeks. While in the Miswak treated group, the animals received 900 mg/kg of body weight of the Miswak aqueous extract daily for the same period. Grossly, at the end of the experiment, our results revealed that the uteri in the Miswak-treated group had characteristics of low active organs; they were pale with low weight and high thickness. In contrast to the treated group, the uteri of the control group had the signs of active organs; they were more vascular, relatively thin and edematous. Microscopically, in the control group, the uterine lumen was wide and the mucosa was folded and covered by secretory columnar epithelium. The uterine glands were more active, and the myometrium was thick. Whereas, in the Miswak-treated group, the lumen was slit-like, the uterine glands were less active, and the uterine wall had thick lamina propria and thin myometrium. In conclusion, the oral administration of Miswak extract reduces the uterus activity. It showed a state of anestrous with a narrow slit-like lumen and a decrease in glandular activit

Research Authors
Sabreen M Ghareeb, Mahmoud Abd-Elkareem, Ahmed Abou-Elmagd
Research Journal
Assuit Veterinary Medical Journal
Research Member
Research Pages
11
Research Publisher
Assuit University,Faculty of veterinary medicine
Research Year
2023

Circulation of thermophilic Campylobacter in pigeons, turkeys, and humans at live bird markets in Egypt

Research Authors
Amal S. M. Sayed, Ahmed I. Ibrahim, Mona M. Sobhy, Ehab Kotb Elmahallawy , Noorah Alsowayeh, Khaloud Mohammed Alarjani, ManalF.El Khadragy and Asmaa Gahlan Youseef
Research Date
Research Department
Research Journal
.Frontiers in Veterinary Science
Research Member
Research Year
2023

Ameliorative effects of propolis and wheat germ oil on acute toxoplasmosis in experimentally infected mice are associated with reduction in parasite burden and restoration of histopathological changes in the brain, uterus, and kidney

Research Authors
Ehab Kotb Elmahallawy, Fatma Abo Zakaib Ali, Enrique Raya-Álvarez, Alaa Fehaid, Khaled A. Abd El-Razik, Hassan Ali Mohamed El Fadaly, Manal F. El-Khadragy, Amal S. M. Sayed, Ashraf H. Soror, Alaa S. Alhegaili, Amira A. Saleh, Abdulsalam A. M. Alkhaldi, Ab
Research Date
Research Journal
Frontiers in Veterinary Science
Research Member
Research Year
2024

Splicing of a myosin phosphatase targeting subunit 1 alternative exon is regulated by intronic cis-elements and a novel bipartite exonic enhancer/silencer element

Research Abstract

Isoforms of the smooth muscle myosin phosphatase targeting subunit 1 (MYPT1) are generated by cassette-type alternative splicing of exons. Tissue-specific expression of these isoforms is thought to determine smooth muscle-relaxant properties and unique responses to signaling pathways. We used mini-gene deletion/mutation constructs to identify cis regulators of splicing of the chicken MYPT1 central alternative exon. Comparisons of alternative exon splicing were made between smooth muscle cells of the fast-phasic contractile phenotype (gizzard), in which the central alternative exon is skipped, and slow tonic contractile phenotype (aorta), in which the alternative exon is included. We demonstrate that splicing of the alternative exon requires a cis-enhancer complex in the vicinity of the alternative exon 5'-splice site. This complex consists of two UCUU motifs in an intronic U-rich sequence (putative PTB (polypyrimidine tract binding) or T cell inhibitor of apoptosis-1 binding sites), an intronic 67-nucleotide enhancer that has similarities with the cardiac Troponin T MSE3 enhancer, and a potentially novel exonic splicing enhancer. The exonic enhancer contains the palindromic sequence UCCUACAUCCU present in many other transcripts where alternative splicing of exons occurs, suggesting that it may be more broadly active. The exonic enhancer is adjacent to a potentially novel exonic silencer element that contains a 13-nucleotide imperfect palindromic sequence. This silencer, in conjunction with a distal intronic silencer, is proposed to mediate the silencing of splicing of the MYPT1 central alternative exon in the fast phasic smooth muscle phenotype

Research Authors
Wessel P Dirksen , Sotohy A Mohamed, Steven A Fisher
Research Date
Research Member
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