Urinary Tract Infection In Rats Research Articles

Antibacterial effect of vitamin C against uropathogenic E. coli in vitro and in vivo

BackgroundResistance to antibiotics has increased steadily over time, thus there is a pressing need for safer alternatives to antibiotics. Current study aims to evaluate the influence of vitamin C as an antibacterial and anti-biofilm agent against uropathogenic E. coli (UPEC) strains. The expression of beta-lactamases and biofilm encoding genes among E. coli isolates before and after treating the isolates with sub MIC of vitamin C was analyzed by Real-time PCR. The in vivo assessment of the antibacterial and anti-biofilm effects of vitamin C against uropathogenic E. coli strains was done using a urinary tract infection (UTI) rat model.ResultsThe effective concentration of vitamin C that could inhibit the growth of most study isolates (70%) was 1.25 mg/ml. Vitamin C showed a synergistic effect with most of the studied antibiotics; no antagonistic effect was detected at all. Vitamin C showed an excellent anti-biofilm effect against studied isolates, where 43 biofilm-producing isolates were converted to non-biofilm at a concentration of 0.312 mg/ml. The expression levels of most studied genes were down-regulated after treatment of E. coli isolates with vitamin C. In vivo assessment of vitamin C in treating UTIs showed that vitamin C has a rapid curative effect as the comparable antibiotic. Administration of both vitamin C and nitrofurantoin at a lower dose for treatment of UTI in rats had a better effect.ConclusionVitamin C as an antibacterial and anti-biofilm agent either alone or in combination with antibiotics could markedly improve UTI in experimental rats.

Bacteriophage Therapy for Escherichia Coli -Induced Urinary Tract Infection In Rats

Background: The present study evaluates the efficacy of bacteriophage therapy for urinary tract infection (UTI) in rats. Methods: UTI was established by inoculating Escherichia coli (100μl) at a concentration of 1.5×108CFU/ml per urethra via a cannula in different groups of rats. For treatment, phage cocktails (200μl) were administered at varying concentrations of 1×108PFU/ml, 1×107PFU/ml and 1×106PFU/ml. Results: The two doses of phage cocktail at the first two concentrations resulted in the cure of UTI. However, the lowest concentration of the phage cocktailwarranted more doses to eradicate the causative bacteria. Conclusion: The quantity, frequency and safety ofdoses could be optimized ina rodent model using the urethral route.

D-Mannose prevents bone loss under weightlessness

BackgroundAstronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness.MethodsThe hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection.ResultsThe TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose.ConclusionD-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.

Protective Effects of Xyloglucan in Association with the Polysaccharide Gelose in an Experimental Model of Gastroenteritis and Urinary Tract Infections.

Acute infectious gastroenteritis (GE) and urinary tract infection (UTI) are common diseases and are normally perceived as mild and limiting illnesses. Xyloglucan is a natural plant polymer with protective barrier properties, also known as “mucosal protectors”, which is the main ingredient of medical devices developed for the management of different diseases, such as gastrointestinal diseases, urinary tract infections, or respiratory allergic diseases. The aim of this study was to evaluate the protective effect of xyloglucan in association with gelose (also called agar) in an experimental model of bacterial GE and UTI in rats. Two kinds of infection were induced by oral administration of Salmonella enterica and Enterococcus hirae for three days. Two days before the bacterial administration, preventive oral treatment with xyloglucan + gelose (10 mg/kg + 5 mg/kg) was performed daily until the seventh day. Twenty-four hours after the last treatment, rats were sacrificed and urinary tracts and intestines for different analysis were collected. The results showed that xyloglucan plus gelose was able to reduce intestinal morphological changes (p < 0.05 for both), tight junctions (TJ) permeability (p < 0.001 for both), and neutrophil infiltration (p < 0.05 for both) induced by bacterial infections, highlighting its barrier proprieties. Moreover, the compound reduced the number of bacterial colonies in the urinary tract favoring elimination by feces. The results obtained in the present study suggest that the protective barrier properties of xyloglucan plus gelose allow the prevention of GE and UTI in models of infections in rats.

Intervention effect and mechanism of curcumin in chronic urinary tract infection in rats

To analyze the invention effect of curcumin on chronic urinary tract infection in rats and explore its possible mechanism of action. The experimental animals were randomly divided into three groups, normal, model and curcumin group. Chronic urinary tract infection models were built for model group and curcumin group by injecting coliform fluid into the cavity of bladder. From the first day of modeling, rats in the curcumin group were injected with 150mg/kg curcumin, while rats in normal group and model group were given no other treatment. The treatment lasted for 14d. The white blood cell counts in blood and urine, bacterial colony count in urine and renal tubular functional indexes of rats in all groups at day 1, 7, and 14 after treatment were detected. Urine β2-microglobulin (β2-MG), urinary N-acetyl-β-D glucosaminidase (NAG) levels were used to detected the inflammatory cytokines in serum after treatment including the contents of IL-6, IL-8, IL-10 and monocyte chemoattractant protein-1 (MCP-1), and real-time PCR was employed to determine the expression of mRNA of toll-like receptor 2 (TLR-2) and TLR-4 in renal tissues and bladder tissues of all groups after treatment. The white blood cell counts at day 1 and 7 after treatment in rats of model group and curcumin group were significantly higher than those of normal group at the same time points, while the white blood cell counts of the curcumin group were significantly lower than those of model group (P<0.05). The urine white blood cell counts in rats of model group at day 1, 7 and 14 were all significantly higher than those of normal group at the same time points; those in the curcumin group were significantly lower than those of the model group at day 1, 7 and 14 at the same time points (P<0.05). The bacterial colony counts of urine in rats of model group and curcumin group at day 1, 7 and 14 were all significantly higher than those of normal group at the same time points, while the counts of curcumin group were significantly lower than those of model group at the same time points (P<0.05). Levels of urine β2-MG, NAG, IL-6, IL-8, IL-10, MCP-1 and expression of TLR2 mRNA and TLR4 mRNA in renal and bladder tissues in rats of model group were significantly higher than those of the normal group, while these variables of the curcumin group were significantly higher than those of the normal group but lower than those of model group (P<0.05). Curcumin can significantly improve the symptoms of chronic urinary tract infections, protect renal tubular function, and also decline inflammatory responses by influencing the expressions of TLR2 mRNA and TLR4 mRNA so as to exert its curative effect on chronic urinary tract infections.

MP23-18 SYNERGISTIC PHOTODYNAMIC THERAPY FOR CATHETER-ASSOCIATED URINARY TRACT INFECTION IN RATS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II1 Apr 2017MP23-18 SYNERGISTIC PHOTODYNAMIC THERAPY FOR CATHETER-ASSOCIATED URINARY TRACT INFECTION IN RATS Anton Wintner, Yingying Huang, Jeffrey Gelfand, Francis McGovern, and Michael Hamblin Anton WintnerAnton Wintner More articles by this author , Yingying HuangYingying Huang More articles by this author , Jeffrey GelfandJeffrey Gelfand More articles by this author , Francis McGovernFrancis McGovern More articles by this author , and Michael HamblinMichael Hamblin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.746AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The rise of multi-drug resistant strains of uropathogenic bacteria is increasing the number of catheter-associated urinary tract infections (CAUTIs), which affect more than one million people per year in the U.S., that are untreatable with current antibiotics. The increase of antibiotic resistance necessitates the need for new antimicrobial treatments that will be effective against multidrug-resistant strains and will not themselves induce resistance. The aim of our study is to demonstrate the feasibility of in vivo treatment of urinary tract infections in rats using photodynamic inactivation (PDI); a method of treatment which uses non-toxic dyes, called photosensitizers, excited with harmless visible light to react with ambient oxygen to produce reactive oxygen species that selectively destroy infecting bacteria while preserving host tissue. METHODS One mL of stable luciferase (lux)-expressing UPEC was inoculated into the bladder of anesthetized female rats via 20 guage angiocatheter placed in the urethra. The progression of the infection and treatment was monitored non-invasively in real time using bioluminescence imaging. The bladder infections in 10 rats were treated by installation of MB [100uM] and KI [100mM] solution after wthich the bladder was illuminated using an optic fiber with 660 nm laser light for 30mins. Serial daily imaging was conducted to document the duration of infection. This was compared to a control group of rats who were infected with UPEC but not treated as well as a group of UPEC infected rats treated only with MB. RESULTS Synergistic UPEC killing effect of PDI (MB + KI) was observed in the PDI treatment group, which demonstrated faster resolution of infection when compared to the control group and MB only group. CONCLUSIONS As both MB and KI are approved for use in the human bladder, an ideal application of this technology would be the treatment of CAUTI in chronically catheterized patients by illuminating MB and KI solution using a laser-coupled catheter with embedded fiber optic light guide called a “photonic Foley catheter.” Our study demonstrates the feasibility of in vivo PDI as a novel approach to treatment of urinary tract infections, which merits further investigation. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e300 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Anton Wintner More articles by this author Yingying Huang More articles by this author Jeffrey Gelfand More articles by this author Francis McGovern More articles by this author Michael Hamblin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Study the therapeutic role of Alcoholic Extract of Plantago lanceolata aganist infection with Staphylococcus saprophyticus

The present study was carried out to investigate the antibacterial activity of alcoholicextracts of Plantago lanceolata leafes in vitro and in vivo by inducing urinary tract infection inrats which caused by urethra administration of S.saprophyticus isolated from human andanimals(cow and sheep)These extracts showed significant effect (P&lt;0.05) on the inhibition of the growth ofS.saprophyticus in vitro with the superiority of the concentration 200mg / ml of alcoholicextract with the mean of inhibition zone diameter 30 mm against S.saprophyticus ,while zonediameter was ( 26.5 ,21 ) mm due to the concentration 150, 100mg/ml respectively.This study included the therapeutic role of doses 150 mg/kg . B.W. of 1.5ml daily orally ofalcoholic extract dissolved in DMSO of plantago lanceolata leaves in the pathogenesis ofS.saprophyticus in rats by the urethral infection in compared with the control group (ratsinjected with S.saprophyticus without treatments).The results of histopathological changesshowed the role of Plantago lanceolata extract on the decreasing of pathological sings inbladder and kidney tissue after 14 and 21 days and gave negative results by decreasecongestion in the blood vessels of kidney hemorrhage and few infiltration of inflammatorycells in bladder , in compared with the positive control which showed acutehistopathological change.

Effects of intravesical liposome-mediated human beta-defensin-2 gene transfection in a mouse urinary tract infection model

The purpose of this study was to assess human β-defensin-2 (hBD-2) gene transfection in human bladder epithelial cells and its therapeutic efficacy in a rat urinary tract infection (UTI) model via liposome mediated gene transfer. A large amount of hBD2 production (36.5 ± 3.2 ng/10(6) cells) was demonstrated in transfected cells' supernatants. In addition, a detectable amount of hBD-2 was identified in rats' urine (4.77 ± 1.4 ng/mL) by ELISA. Expression of the transgene hBD-2 in transfected cells and rats' bladders was also confirmed by RT-PCR and Western blotting. Immunohistochemistry revealed that the transgene hBD-2 expressed in the entire epithelial layer of the transduced bladders. Numbers of bacterial colony-forming units in urine and bladders from hBD2 gene treated UTI rats were significantly lower than those from the UTI rats administered PBS at 24, 36, and 72 hr after infection (P < 0.05). In addition, in vivo expression of hBD-2 reduced mucosal damage, interstitial edema and inflammatory cell infiltration in UTI animals. The results indicate that successful inhibition of UTI progression can be produced by hBD2 gene therapy. The liposome-mediated hBD2 plasmid DNA transfection system appears to be a promising method for antimicrobial gene therapy of UTI.

BIOCOMPATIBILITY OF NITINOL AND STAINLESS STEEL IN THE BLADDER: AN EXPERIMENTAL STUDY

We tested the biocompatibility of nitinol, a nickel titanium alloy, and stainless steel (SS) as bladder implant materials. Rats received a nitinol implant, an SS implant or were sham controls. Two, 3, 6 and 8 weeks following implantation 24-hour voiding behavior studies were performed to investigate bladder irritation. All animals were sacrificed 8 weeks after implantation and a sample of urine was aspirated for culture. The bladders were examined by light microscopy and scanning electron microscopy (SEM). No visible encrustations or infections were noted in urine. Voiding frequency in the light period 6 weeks after implantation was significantly decreased in the 2 implant groups compared with sham controls. There were no other significant differences in frequency or mean volume per void in the light or dark periods at any time point. Light microscopy demonstrated similar implant tissue effects in all groups with little or no inflammation or fibrosis. Under SEM all implants showed a brittle, amorphous coating devoid of cells. The transition between the urothelium mucosa and the rod was smoother for SS than for nitinol, suggesting an affinity of SS for mucosa. In all nitinol rods discontinuity was present between the mucosa and rod. Nitinol and SS do not cause more irritation than the effects of surgery alone and the 2 materials seem to be biocompatible in the bladder. Nitinol may be more inert than SS based on SEM results.

A gene, uge, is essential for Klebsiella pneumoniae virulence.

Klebsiella pneumoniae strains typically express both smooth lipopolysaccharide (LPS) with O antigen molecules and capsule polysaccharide (K antigen) on the surface. A single mutation in a gene that codes for a UDP galacturonate 4-epimerase (uge) renders a strain with the O-:K- phenotype (lack of capsule and LPS without O antigen molecules and outer core oligosaccharide). The uge gene was present in all the K. pneumoniae strains tested. The K. pneumoniae uge mutants were unable to produce experimental urinary tract infections in rats and were completely avirulent in two different animal models (septicemia and pneumonia). Reintroduction of the single uge wild-type gene in the corresponding mutants completely restored the wild-type phenotype (presence of capsule and smooth LPS) independently of the O or K serotype of the wild type. Furthermore, complemented uge mutants recovered the ability to produce experimental urinary tract infections in rats and virulence in the septicemia and pneumonia animal models.

The cell-bound hemolysin of Serratia marcescens contributes to uropathogenicity

The contribution of the cell-bound hemolysin of Serratia marcescens to uropathogenicity was studied in an experimental urinary tract infection in rats. The strain carrying the Serratia hemolysin colonized the urinary tract more and lead to a stronger inflammatory response compared to the isogenic hemolysin negative strain.

Activity of sulbactam/ampicillin in screening and discriminative animal models of infection.

The efficacy of sulbactam/ampicillin in the treatment of mice with fatal systemic infections produced by ampicillin-resistant Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, or Proteus vulgaris strains is well established. In this paper the demonstrations of efficacy for sulbactam/ampicillin have been extended to a number of clinically relevant models, including bacteremia and meningitis produced by H. influenzae in infant rats, experimental staphylococcal endocarditis in rabbits, localized lesions in mice, urinary tract infections in rats, and prophylaxis in a surgical wound model in mice. In these models, in which ampicillin-resistant organisms were used, sulbactam/ampicillin was either more effective than or as effective as appropriate control agents. Neither sulbactam nor ampicillin used separately displayed significant activity. The results of supportive pharmacokinetic studies, in which differential bioassays were used, demonstrated that sulbactam and ampicillin generally were delivered with equal efficiency to plasma and to extravascular fluids obtained by sampling the contents of implanted cylinders.

Urothelial Hyperplasia and Neoplasia. II. Detection of Nitrosamines and Interferon in Chronic Urinary Tract Infections in Rats

AbstractIn rats with chronic urinary tract infections, urine and blood were examined for two classes of compounds (nitrosamines and interferon) which may lead to the development of urothelial hyperplasia and neoplasia. In vitro, Escherichia coli, a Proteus species or a mixture of both were able to induce high levels of interferon which theoretically could reduce the host’s cellular immune surveillance. These high levels were not detected in vivo in either short-term (5 hr. to 2 wk.) or long-term (2 wk. to 24 wk.) infected rats. In contrast, N, N dimethylnitrosamine was detected in the majority (≥ 50 per cent) of long term infected rats after 12 wk. although individual rats showed detectable levels as early as 2 wk. post infection. Sterile human or rat urine supported bacterial growth and subsequent production of N, N dimethylnitrosamine, but only after 16 wk. of subculturing in vitro. Gas chromatography was able to detect small amounts of nitrosamines extracted from urine. The mass spectrometer yielded quantitatively and qualitatively better detection. With long term infections, the appearance of a potential carcinogen, N, N dimethylnitrosamine, occurs in vivo and in vitro and correlates with previous findings that describe the development of hyperplastic and early neoplastic changes in the rat urothelium.

Prevention of urinary tract infection in rats with an indigenous Lactobacillus casei strain.

Our previous studies have shown that indigenous bacteria are able to block the in vitro attachment of uropathogenic bacteria to human uroepithelial cells. In the present study, we applied the concept of competitive exclusion to an animal model. A chronic urinary tract infection was established in female rats with bacteria incorporated into agar beads injected periurethrally into the urinary bladder via a no. 3 French ureteral catheter. Five strains of uropathogenic organisms were used in the first set of experiments, and their colonization of the bladder and kidneys of the animals was confirmed up to 2 months after injection. The uropathogens stimulated an immune response, detected by serum antibodies against the uropathogens, and an inflammatory response noted in sections of the kidneys stained with hematoxylin and eosin. Using this animal model, we established the persistent adherence of bacteria in the urinary tract without the need for creation of obstruction or implantation of a foreign body. In a second set of experiments, an isolate of Lactobacillus casei GR1 taken from the urethra of a healthy woman was incorporated into agar beads, instilled within the rat bladders on day 1, and then swabbed twice weekly for 21 days onto the introitus before challenge with uropathogens instilled into the urinary bladder. In 21 of 25 animals, no uropathogenic bacteria were recovered from the bladder and kidney tissues up to 60 days after challenge, and no immune response was detected. Our results show that L. casei prevented onset of urinary tract infection in 84% of the animals tested. The lactobacilli appeared to exclude the uropathogens from colonizing the urinary tract, within the first 48 hours after challenge, and the net effect was a complete eradication of bacteria from the uroepithelium. It is hoped that the demonstration of a protective role for indigenous bacteria in preventing urinary tract infection in an animal model will lead to the application of this technology to prevent recurrent urinary tract infection in female patients.

Urothelial Hyperplasia and Neoplasia: A Response to Chronic Urinary Tract Infections in Rats

The rat was used as an animal model to examine the effect of foreign bodies and long term infection (24 weeks) on bladder epithelium. Stainless steel wire implants and multiple injections of Escherichia coli were compared to control rat bladders by gross observation, light microscopy and scanning electron microscopy. Hyperplastic alterations, (papilloma, von Brunn’s nests), dysplasia (squamous metaplasia, microvilli) and early lesions consistent with neoplasia occurred in rats with bladder implants and multiple bacterial injections but not in controls. Epithelial changes were not associated with sterile bladder implants. Bladder papillomata could be observed as early as 2 weeks in rats having both an implant and an infection, but the majority of hyperplastic and early neoplastic-like changes occurred after 6 weeks. Long-term infections, both with and without a bladder implant, can lead to lesions consistent with neoplasia in bladder epithelium.

Ventral bladder hernia facilitates study of urinary tract infections in rats.

Previous studies have demonstrated that after intravesical inoculation of Escherichia coli, rats drinking 5% glucose-water remained bacteriuric for up to 21 days while rats drinking tap water became abacteriuric within a few days. To facilitate accurate monitoring of bacteriuria, we created a ventral bladder hernia for percutaneous aspiration of urine. After intravesical inoculation with 10(8) E. coli, rats with ventral bladder hernias demonstrated clearance of bacteria at a rate comparable to that observed in rats with intrapelvic bladders (p less than 0.01). Of rats drinking tap water, 6 of 7 (85%) with intrapelvic bladders and 8 of 9 (89%) with ventral hernias had less than 10 colony forming units per ml of urine within 9 days of inoculation. Of rats drinking 5% glucose-water, 4 of 5 (80%) with intrapelvic bladders and 6 of 8 (75%) with ventral bladder hernias had greater than 10(5) colony forming units per ml of urine 9 days after inoculation. The results suggest that this technique does not alter the antibacterial response of control or polyuric rats to E. coli inoculated intravesically.

Experimental Urinary Tract Infection in Rats Caused by Candida albicans

The increased clinical use of broad-spectrum antibiotics, immunosuppressives, and anti-inflammatory agents is thought to have contributed to the increased incidence of renal infections due to Candida albicans. To aid in the search for improved anticandidal agents, we developed an experimental model in which C. albicans is injected into the medulla of the surgically exposed kidney of the rat. The ensuing infection is restricted to the urinary tract and can be treated successfully with amphotericin B. This model promises to be of merit in the evaluation of agents potentially useful in treating candidiasis of the urinary tract.

Activity of tetracyclines, nalidixic acids, and nitrofurantoin in two experimental models of Escherichia coli urinary tract disease in rats.

SummaryOxytetracycline, α-6-deoxyoxytetracycline, nitrofurantoin, and nalidixic acid were studied in two experimental Escherichia coli models of urinary tract infection in rats, i.e., descending pyelonephritis induced by intravenous injection of the organism after temporary ureter occlusion and ascending pyelonephritis induced by administration of the organism into the bladder followed by manually produced reflux.Oxytetracycline and α-6-deoxyoxytetracycline, agents which appear in active form in body fluids and tissues, had equal activity in both infection models. Although nitrofurantoin appears in active form only in the urine, equal activity was demonstrated in both infection models. Nalidixic acid, an agent primarily active in the urine, was markedly more active in the ascending than in the descending urinary infection model. A more critical and complete appraisal of chemotherapeutants for use in urinary tract disease would be gained by evaluation in 2 different experimental urinary tract models rather...

The effect of oestrogen upon ascending urinary tract infection in rats.

SUMMARY Rats were inoculated transurethrally with E. coli 14 days after treatment with ostrogen, 35 days after treatment with ostrogen, or without ostrogen therapy. The ostrogen produced gross hydronephrosis in 82 per cent, of the animais after 28 days of therapy and 100 per cent, by day 63. The animais inoculated 14 days after ostrogen treatment had begun handled their infections as well as the controls, but those that were treated for 35 days developed persistent high colony counts in the bladder and kidneys. Histological changes of the urinary tract produced by ostrogen therapy and possible correlations to the persistent bacteriuria of pregnancy are discussed.