1.Fosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue of rats with chronic bacterial prostatitis.
Wen-Wei CAI ; Dun-Sheng MO ; Ming FAN ; Hong-Cai CAI ; Guo-Wei ZHANG ; Wei-Piong WANG ; Xue-Jun SHANG
National Journal of Andrology 2018;24(6):491-498
ObjectiveTo investigate the effects of fosfomycin tromethamine (FT) on the expressions of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in the prostate tissue of the rats with chronic bacterial prostatitis (CBP).
METHODSWe randomly divided 70 male SD rats into 7 groups of equal number: blank control, CBP model control, positive control, 14 d low-dose FT, 7 d low-dose FT, 14 d high-dose FT, and 7 d high-dose FT. The CBP model rats in the latter five groups were treated intragastrically with levofloxacin at 100 mg/kg/d for 30 days and FT at 200 mg/kg/d for 14 and 7 days and at 300 mg/kg/d for 14 and 7 days, respectively. Then we collected the prostate tissue from the animals for determination of the levels of TNF-α, IL-8 and IL-6 by ELISA.
RESULTSCompared with the blank controls, the CBP model rats showed significantly increased levels of TNF-α ([19.83 ± 6.1] vs [32.93 ± 6.21] ng/g prot, P <0.01), IL-8 ([8.26 ± 0.52] vs [16.2 ± 2.84] ng/g prot, P <0.01) and IL-6 ([1.55 ± 0.11] vs [2.51 ± 1.06] ng/g prot, P <0.05) in the prostate tissue. In comparison with the CBP model controls, the levels of TNF-α and IL-8 were remarkably decreased in the groups of positive control ([20.54 ± 5.78] ng/g prot, P <0.01; [12.43 ± 4.02] ng/g prot, P <0.05), 14 d low-dose FT ([21.95 ± 6.48] ng/g prot, P <0.01; [11.11 ± 2.86] ng/g prot, P <0.01), 7 d low-dose FT ([23.8 ± 6.93] ng/g prot, P <0.05; [12.43 ± 4.02] ng/g prot, P <0.05), 14 d high-dose FT ([19.97 ± 2.58] ng/g prot, P <0.01; [8.83 ± 1.32] ng/g prot, P <0.01), and 7 d high-dose FT ([21.97 ± 3.38] ng/g prot, P <0.01; [12.68±1.97] ng/g prot, P <0.05). No statistically significant differences were observed between the positive control and FT groups in the contents of TNF-α, IL-8 or IL-6 (P >0.05). The expression of IL-6 was markedly reduced in the 14 d high-dose FT group as compared with the model controls ([1.76 ± 0.46] vs [2.51 ± 1.06] ng/g prot, P<0.05) but exhibited no significant difference between the CBP model control and the other groups (P >0.05).
CONCLUSIONSFosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue, suppresses its inflammatory reaction, promotes the repair of damaged prostatic structure, and thus contributes to the treatment of chronic bacterial prostatitis in rats.
Animals ; Anti-Bacterial Agents ; pharmacology ; Bacterial Infections ; drug therapy ; microbiology ; Fosfomycin ; pharmacology ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Levofloxacin ; pharmacology ; Male ; Prostate ; drug effects ; metabolism ; Prostatitis ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism
2.Cefoxitin plus levofloxacin for prevention of severe infection after transrectal prostate biopsy.
Rong-Bing LI ; Xiao-Fei WEN ; Yue-Min WANG ; Wei-Hua CHEN ; Xue-Lei WANG ; Ji-Ling WEN ; Lin-Jie SHEN
National Journal of Andrology 2018;24(4):322-326
ObjectiveTo evaluate the effect of cefoxitin prophylactic in reducing the incidence of severe infection after transrectal prostate biopsy (TRPB).
METHODSThis retrospective study included 155 cases of TRPB with a 5-day administration of oral levofloxacin at 200 mg bid (the control group) and another 167 cases with a 3-day administration of oral levofloxacin at the same dose plus intravenous cefoxitin at 2.0 g 2 hours before TRPB (the experimental group) according to the distribution characteristics of drug-resistance bacteria in our department. The patients of the control and experimental groups were aged (68.68 ± 8.12) and (68.72 ± 7.51) years, with PSA levels of (19.78 ± 21.57) and (21.15 ± 42.63) μg/L, involving (11.68 ± 1.44) and (11.77±1.02) biopsy cores, respectively. Comparisons were made between the two groups of patients in the incidence rate of severe infection, which was defined as lower urinary track symptoms plus the systemic inflammatory response syndrome (SIRS) within 7 days after TRPB.
RESULTSThe incidence rate of postoperative severe infection was significantly lower in the experimental group than in the control (0.6% [1/167] vs 5.8% [9/155], P < 0.05). Blood cultures revealed positive E-coli strains in 6 cases in the control group, including 5 ESBL-positive and 4 quinolone-resistant and amikacin-sensitive cases, all sensitive to cefoxitin, cefoperazone/sulbactam and imipenem. The only one case of severe infection was shown to be negative in blood culture.
CONCLUSIONSPreoperative intravenous administration of cefoxitin according to the specific distribution characteristics of drug-resistance bacteria can significantly reduce the incidence of severe infection after TRPB.
Aged ; Anti-Bacterial Agents ; therapeutic use ; Biopsy ; adverse effects ; methods ; Cefoxitin ; therapeutic use ; Drug Resistance, Bacterial ; Escherichia coli ; isolation & purification ; Escherichia coli Infections ; microbiology ; prevention & control ; Humans ; Levofloxacin ; therapeutic use ; Male ; Middle Aged ; Postoperative Complications ; blood ; prevention & control ; Prostate ; pathology ; Retrospective Studies
3.Anti-inflammatory and Antimicrobial Effects of Anthocyanin Extracted from Black Soybean on Chronic Bacterial Prostatitis Rat Model.
Byung Il YOON ; Woong Jin BAE ; Yong Sun CHOI ; Su Jin KIM ; U Syn HA ; Sung-Hoo HONG ; Dong Wan SOHN ; Sae Woong KIM
Chinese journal of integrative medicine 2018;24(8):621-626
OBJECTIVETo investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis (CBP) rat model.
METHODSThe Sprague-Dawley rats were divided into 4 groups, including control, ciprofloxacin, anthocyanins and anthocyanins with ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial suspension (Escherichia coli Z17 O:K:H) into Sprague-Dawley rats was conducted to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and histological analysis on the prostate were analyzed for each group.
RESULTSThe use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05).
CONCLUSIONSThese results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.
Acinar Cells ; drug effects ; pathology ; Animals ; Anthocyanins ; isolation & purification ; pharmacology ; therapeutic use ; Anti-Infective Agents ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Chronic Disease ; Disease Models, Animal ; Escherichia coli Infections ; drug therapy ; urine ; Fibrosis ; Inflammation ; pathology ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Prostate ; drug effects ; microbiology ; pathology ; Prostatitis ; drug therapy ; microbiology ; urine ; Rats, Sprague-Dawley ; Severity of Illness Index ; Soybeans ; chemistry ; Urine ; microbiology
4.Bone marrow mesenchymal stem cells suppress E coli-induced bacterial prostatitis in rats.
Guang-wei HAN ; Cheng-cheng LIU ; Wen-hong GAO ; Dong CUI ; Shan-hong YI
National Journal of Andrology 2015;21(4):294-299
OBJECTIVETo investigate the inhibitory effect of bone marrow mesenchymal stem cells (BMSCs) on E coliinduced prostatitis in rats.
METHODSBMSCs were isolated, cultured and amplified by the attached choice method. Fifty SD rats were randomized into five groups of equal number: normal control, acute bacterial prostatitis (ABP) , chronic bacterial prostatitis (CBP), ABP + BMSCs, and CBP + BMSCs, and the animals in the latter four groups were injected with E. coli into both sides of the prostate under ultrasound guidance for 1 - 14 days to induce ABP and for 4 - 12 weeks to induce CBP. The control rats were injected with the same amount of PBS. Two weeks after injection of BMSCs into the prostates, pathomorphological changes in the prostate were observed under the light microscope and the mRNA and protein levels of IL-1β and TNF-α determined by RT-PCR and ELISA, respectively, followed by statistical analysis with SPSS 18.0.
RESULTSHistopathological evaluation showed typical pathological inflammatory changes in the prostates of the rats in the ABP and CBP groups, including glandular structural changes, interstitial edema, inflammatory cell infiltration, and fibrous hyperplasia, which were all remarkably relieved after treated with BMSCs. The mRNA and protein levels of IL-β ([0.829 ± 0.121] and [271.75 ± 90.59] pg/ml) and TNF-α ([0.913 ± 0. 094] and [105.78 ± 19. 05] pg/ml) in the ABP and those of IL-1β ([0. 975 ± 0. 114] and [265. 31 ± 71. 34] pg/ml) and TNF-α ([0. 886 ± 0. 084] and [107. 45 ± 26. 11 ] pg/ml) in the CBP groups were significantly higher than those in the control rats ([0. 342 ± 0.087] and [45.76 17. 99] pg/ml, P <0. 05); ([0.247 ± 0.054] and ([19.42 ± 7. 75] pg/ml, P <0. 01) as well as than those in the ABP + BMSCs ([0. 433 ± 0. 072] and [51. 34 ± 22. 13] pg/ml, P < 0. 05 ) ; ( [0. 313 ± 0. 076] and [28. 38 ± 8. 78] pg/ml, P < 0. 01) and the CBP + BMSCs group ([0.396 ± 0.064] and [56.37 ± 21.22] pg/ml, P <0.05); ([0.417 ± 0.068] and [29.21 ± 10.22] pg/ml, P <0.01).
CONCLUSIONInjection of BMSCs can reduce E coli-induced prostatic inflammation reaction, which.may be associated with its reduction of inflammatory cell infiltration and the expressions of IL-1β and TNF-α in the prostate tissue.
Acute Disease ; Animals ; Bone Marrow Cells ; physiology ; Chronic Disease ; Escherichia coli Infections ; therapy ; Humans ; Interleukin-1beta ; genetics ; Male ; Mesenchymal Stromal Cells ; physiology ; Prostate ; metabolism ; Prostatitis ; metabolism ; microbiology ; therapy ; RNA, Messenger ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; metabolism
5.Infection after transrectal ultrasound-guided prostate biopsy.
Korean Journal of Urology 2015;56(5):346-350
		                        		
		                        			
		                        			Infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-Bx) appear to be increasing, which reflects the high prevalence of antibiotic-resistant strains of Enterobacteriaceae. Identifying patients at high risk for antibiotic resistance with history taking is an important initial step. Targeted prophylaxis with a prebiopsy rectal swab culture or augmented antibiotic prophylaxis can be considered for patients at high risk of antibiotic resistance. If infectious complications are suspected, the presence of urosepsis should be evaluated and adequate antibiotic treatment should be started immediately.
		                        		
		                        		
		                        		
		                        			Anti-Bacterial Agents/therapeutic use
		                        			;
		                        		
		                        			Antibiotic Prophylaxis
		                        			;
		                        		
		                        			Biopsy/*adverse effects
		                        			;
		                        		
		                        			Drug Resistance, Bacterial
		                        			;
		                        		
		                        			Escherichia coli Infections/drug therapy/*prevention & control
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Prostate/*pathology
		                        			;
		                        		
		                        			*Ultrasound, High-Intensity Focused, Transrectal
		                        			;
		                        		
		                        			Urinary Tract Infections/*drug therapy/microbiology
		                        			
		                        		
		                        	
6.Pathogens in expressed prostatic secretion and their correlation with serum prostate specific antigen: analysis of 320 cases.
Shu-Xia WANG ; Jia-Ming ZHANG ; Kai WU ; Juan CHEN ; Jian-Feng SHI
National Journal of Andrology 2014;20(8):715-718
OBJECTIVETo investigate the pathogenic infection and its drug resistance in expressed prostatic secretion (EPS) and its correlation with serum PSA, and provide some evidence for the systematic and normalized diagnosis and treatment of prostatitis.
METHODSThree EPS swabs were collected from each of the 320 prostatis patients following measurement of the serum PSA level, 1 for bacterial culture and identification, 1 for detection of Mycoplasma and drug sensitivity, and the other for examination of Chlamydia trachomatis antigen by colloidal gold immunoblot.
RESULTSTotally 244 strains were isolated from the 320 EPS samples, including 188 bacterial strains (dominated by Staphylococcus and sensitive to vancomycin or linezolid) and 44 Mycoplasma and Chlamydia strains (mainly Ureaplasma urealyticum and susceptible to josamycin or doxycycline). The serum PSA level was significantly higher in the pathogen-positive than in the pathogen-negative group ([6.98 +/- 0.56] microg/L vs [2.32 +/- 0.12] microg/L, P < 0.05).
CONCLUSIONProstatitis may lead to the elevation of the serum PSA level and the pathogens involved vary in their resistance to different antibacterial spectrums. Therefore, appropriate and individualized antibiotic therapy should be selected according to etiological diagnosis and the results of drug sensitivity test.
Adult ; Humans ; Male ; Middle Aged ; Prostate ; microbiology ; secretion ; Prostate-Specific Antigen ; blood ; Prostatitis ; blood ; microbiology ; Young Adult
7.Roles of adenosine and cytokines in the prostate tissue of rats with acute bacterial prostatitis.
Zhi LONG ; Xia-Ming PEI ; Le-Ye HE ; Ying-Bo DAI ; Dong-Yi PENG ; Yi-Chuan ZHANG ; Xuan-Yan SHI ; Jing-Liang HE
National Journal of Andrology 2014;20(4):315-319
OBJECTIVETo investigate the possible roles of adenosine and the cytokines TNF-alpha and IL-10 in the pathogenesis of acute bacterial prostatitis (ABP) in rats.
METHODSForty-eight male Wistar rats were randomly divided into groups A (ABP), B (ABP + theophylline intervention), C (sham) and D (blank control). ABP models were established by injecting Escherichia coli 0157 into the prostate, and those in group B were treated by intraperitoneal injection of theophylline immediately after modeling. At 4 and 14 days, the prostate tissues of the rats were collected for detection of the expressions of TNF-alpha and IL-10 by immunohistochemistry and the concentration of adenosine by high-performance liquid chromatography.
RESULTSAt 4 and 14 days, the concentrations of adenosine were significantly higher in group A ([48.38 +/- 17.27] and [26.54 +/- 11.22] microg/g) than in C ([0.45 +/- 0.25] and [0.46 +/- 0.29] microg/g) and D ([0.41 +/- 0.23] and [0.43 +/- 0.27] microg/g) (P < 0.05), and so were the expressions of TNF-alpha in A (0.23 +/- 0.08 and 0.21 +/- 0.03) than in C (0.07 +/- 0.03 and 0.07 +/- 0.01) and D (0.07 +/- 0.06 and 0.07 +/- 0.06) (P < 0.05), and those of IL-10 in A (0.13 +/- 0.03 and 0.25 +/- 0.01) than in C (0.07 +/- 0.03 and 0.07 +/- 0.03) and D (0.07 +/- 0.01 and 0.07 +/- 0.02) (P < 0.05). Compared with group A, the rats in group B showed significant increases at 4 and 14 days in the severity of inflammation, concentration of adenosine ([86.64 +/- 32.87] and [51.17 +/- 22.96] microg/g, P < 0.05) and expression of TNF-alpha (0.37 +/- 0.08 and 0.32 +/- 0.06, P < 0.05), but exhibited no remarkable difference in the expression of IL-10 (0.12 +/- 0.06 and 0.15 +/- 0.06, P > 0.05).
CONCLUSIONAdenosine may affect the progression of inflammation by regulating the expressions of the cytokines TNF-alpha and IL-10 in ABP rats through the adenosine receptor signaling pathway.
Adenosine ; physiology ; Animals ; Escherichia coli O157 ; Interleukin-10 ; metabolism ; Male ; Prostate ; drug effects ; metabolism ; Prostatitis ; metabolism ; microbiology ; Random Allocation ; Rats ; Rats, Wistar ; Theophylline ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism
8.A Prospective Korean Multicenter Study for Infectious Complications in Patients Undergoing Prostate Surgery: Risk Factors and Efficacy of Antibiotic Prophylaxis.
Eu Chang HWANG ; Seung Il JUNG ; Dong Deuk KWON ; Gilho LEE ; Jae Hyun BAE ; Yong Gil NA ; Seung Ki MIN ; Hwancheol SON ; Sun Ju LEE ; Jae Min CHUNG ; Hong CHUNG ; In Rae CHO ; Young Ho KIM ; Tae Hyoung KIM ; In Ho CHANG
Journal of Korean Medical Science 2014;29(9):1271-1277
		                        		
		                        			
		                        			This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anti-Bacterial Agents/pharmacology/therapeutic use
		                        			;
		                        		
		                        			Antibiotic Prophylaxis
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2/complications
		                        			;
		                        		
		                        			Drug Resistance, Bacterial/drug effects
		                        			;
		                        		
		                        			Enterococcus/drug effects/isolation & purification
		                        			;
		                        		
		                        			Escherichia coli/isolation & purification
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Klebsiella pneumoniae/drug effects/isolation & purification
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Odds Ratio
		                        			;
		                        		
		                        			Postoperative Complications/microbiology/prevention & control
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Prostatic Neoplasms/complications/*surgery
		                        			;
		                        		
		                        			Quinolones/pharmacology
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Time Factors
		                        			;
		                        		
		                        			Transurethral Resection of Prostate
		                        			;
		                        		
		                        			Urinalysis
		                        			;
		                        		
		                        			Urinary Tract Infections/microbiology
		                        			
		                        		
		                        	
9.Drug penetrability and etiologic diagnosis and treatment of prostatitis in men.
National Journal of Andrology 2012;18(9):771-776
		                        		
		                        			
		                        			The prostate gland, like other glandular organs, is rich in blood and lymphatic vessels and nerves, which are the important histological factors for obtaining nutrition as well as for the endocrine and exocrine functions of the glands. Antimicrobial and non-antimicrobial drugs administered to patients by the oral, IM, IV or even topical routes are absorbed into the blood and transported to the prostate and other organs, where they can diffuse into the extravascular tissues through the walls of normal and damaged capillaries. The permeability of the prostate is enhanced by inflammatory reactions in the prostatic tissue, which is responsible for exudation or leakage of leukocytes and red blood cells, and drugs in the blood can enter the extravascular tissue of the prostate as well as diffuse into the prostatic secretions. The prostate lesions in patients with prostatitis or other prostatic diseases are caused by different types of pathogenic agents with various properties, and these diseases are characterized by a longer process of damage and a variety of pathological changes. Therefore, the diagnosis and treatment of prostatitis are relatively complex and difficult challenges hut meanwhile simple and easy matters for clinicians, and the difficulty or easiness is related not to the drug penetrability of the prostate, but largely to the understanding of the biological properties of the pathogenic agents, the physiological and pathological conditions of the patient's body and prostate, and the properties of drugs. The common factors that cause difficult treatment of prostatitis include clinical and laboratory misdiagnoses, release of pathogenic agents within pyogenic or necrotic prostatic tissues, variation of pathogenic agents, reinfection by other pathogens, and choice and administration of drugs.
		                        		
		                        		
		                        		
		                        			Anti-Bacterial Agents
		                        			;
		                        		
		                        			pharmacokinetics
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Prostate
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			microbiology
		                        			;
		                        		
		                        			pathology
		                        			;
		                        		
		                        			Prostatitis
		                        			;
		                        		
		                        			diagnosis
		                        			;
		                        		
		                        			microbiology
		                        			;
		                        		
		                        			pathology
		                        			
		                        		
		                        	
10.Effects of Prostate Water Pellets on the number of colonies, NO concentration and NOS activity in the prostate tissue of CBP rats.
Yi-Ming SUN ; Yue LI ; Li LIU ; Wen-Quan ZHU ; Guo-Hua JIANG
National Journal of Andrology 2010;16(4):373-376
OBJECTIVETo investigate the effects of Prostate Water Pellets (PWP) on the number of colonies, NO concentration and NOS activity in the prostate tissues of rats with chronic bacterial prostatitis (CBP).
METHODSA total of 120 healthy adult male Wistar rats weighing 250-300 g were equally randomized into 6 groups: blank control, model control, positive control, high-dose PWP, medium-dose PWP and low-dose PWP. The CBP rat models were established by injecting colibacilli (10(7)/ml) into the prostate. A month later, the high- , medium- and low-dose PWP groups were treated intragastrically with PWP at 4.4 g/kg, 2.2 g/kg and 1.1 g/kg per day respectively, the positive controls with levofloxacin at 0.018 g/kg per day, and the blank and model controls with normal saline, all for 35 days. Then the numbers of colonies in the prostate tissues were measured, and the changes in NO concentration and NOS activity detected by the nitrite reductase method.
RESULTSCompared with the model controls, the number of colonies, NO concentration and NOS activity were significantly reduced in the prostate tissues of the rats of the high- , medium- and low-dose PWP groups (P < 0.01).
CONCLUSIONPWP was proved to be efficacious for CBP in rats, whose mechanism might be related with its inhibitory effect on bacterial growth and decreasing effect on NO concentration and NOS activity in the prostate tissues.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Phytotherapy ; Prostate ; metabolism ; microbiology ; Prostatitis ; drug therapy ; metabolism ; microbiology ; Rats ; Rats, Wistar
            
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