Effects of vancomycin, daptomycin, and tigecycline on coagulase-negative staphylococcus biofilm and bacterial viability within biofilm: an in vitro biofilm model.

Bacteria may hide in a hydrated polysaccharide matrix known as a biofilm. The structure of the bacterial biofilm renders phagocytosis difficult and increases antibiotic resistance. We hypothesized that repeated doses of antibiotics have an effect on bacteria within the biofilm and that it could inhibit or eradicate biofilm formation. Two clinical biofilm-positive coagulase-negative staphylococcus isolates were evaluated. The effects of antibiotics on preformed and nascent biofilm and on bacterial eradication within the biofilm were determined using different doses of vancomycin, daptomycin, and tigecycline for different durations in an in vitro biofilm model. Vancomycin neither penetrated the biofilm nor had any microbicidal effect on bacteria within the biofilm. Daptomycin had a microbicidal effect on bacteria within the biofilm but had no effect on biofilm inhibition and eradication (independent from dose and treatment time). Tigecycline inhibited and eradicated biofilm formation and had a microbicidal effect on bacteria within the biofilm. In conclusion, (i) biofilm formation appeared to be a major barrier to vancomycin activity, (ii) daptomycin had an antimicrobial effect on the bacteria within the biofilm but not on the biofilm burden, and (iii) tigecycline had effects both on bacteria within the biofilm and on biofilm burden. Thus, both tigecycline and daptomycin might be promising candidates for the treatment of biofilm infections.

Renal cyst infection caused by Brucella abortus.

A 49-year-old man with a medical history of polycystic kidney disease was presented to the emergency department with fever and left flank pain. Abdominal examination revealed an enlarged and painful left kidney. The C-reactive protein level was significantly high and the magnetic resonance imaging revealed areas of abnormal intensity and fluid-fluid levels in renal cysts. Brucella abortus was yielded from both blood and cyst fluid culture. Standard therapy (rifampicin plus doxycycline) of brucellosis was started, but the clinical and laboratory signs subsided after the addition of ciprofloxacin. There was no need for aspiration of infected cyst fluid. Hereby, according to the medical database search, we report that the first renal cyst infection caused by B. abortus was successfully treated with triple antibiotic therapy.

Nonionic, water self-dispersible "hairy-rod" poly(p-phenylene)-g-poly(ethylene glycol) copolymer/carbon nanotube conjugates for targeted cell imaging.

The generation and fabrication of nanoscopic structures are of critical technological importance for future implementations in areas such as nanodevices and nanotechnology, biosensing, bioimaging, cancer targeting, and drug delivery. Applications of carbon nanotubes (CNTs) in biological fields have been impeded by the incapability of their visualization using conventional methods. Therefore, fluorescence labeling of CNTs with various probes under physiological conditions has become a significant issue for their utilization in biological processes. Herein, we demonstrate a facile and additional fluorophore-free approach for cancer cell-imaging and diagnosis by combining multiwalled CNTs with a well-known conjugated polymer, namely, poly(p-phenylene) (PP). In this approach, PP decorated with poly(ethylene glycol) (PEG) was noncovalently (π-π stacking) linked to acid-treated CNTs. The obtained water self-dispersible, stable, and biocompatible f-CNT/PP-g-PEG conjugates were then bioconjugated to estrogen-specific antibody (anti-ER) via -COOH functionalities present on the side-walls of CNTs. The resulting conjugates were used as an efficient fluorescent probe for targeted imaging of estrogen receptor overexpressed cancer cells, such as MCF-7. In vitro studies and fluorescence microscopy data show that these conjugates can specifically bind to MCF-7 cells with high efficiency. The represented results imply that CNT-based materials could easily be fabricated by the described approach and used as an efficient "fluorescent probe" for targeting and imaging, thereby providing many new possibilities for various applications in biomedical sensing and diagnosis.

The seroprevalence of Crimean-Congo haemorrhagic fever among inhabitants living in the endemic regions of Western Anatolia.

BACKGROUND: In Turkey, Crimean-Congo haemorrhagic fever (CCHF) is seen particularly in the north-eastern part of Anatolia. Aydin was thought to be a non-endemic area, however the first case was reported from Aydin in 2006 and a total of 39 cases were reported between 2006 and 2010. METHODS: Four hundred and twenty-nine volunteers from 3 endemic regions of Aydin were enrolled in this study. We determined the IgG seropositivity against the virus by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: IgG seropositivity in the study group was found to be 19.6% (n = 84). Chi-squared automatic interaction detector (CHAID) analysis was performed and a significant relationship between IgG seropositivity and tick-bite was found. The IgG seropositivity rate was 13% in cases without a history of tick-bite, while it was 41.1% in those with a tick-bite history (p < 0.001). In cases without a history of tick-bite (n = 339), the most important factor related to seropositivity was cattle-dealing. The seropositivity rate was higher in women than in men in the group dealing with cattle without a history of tick-bite (p = 0.013). In cases with a tick-bite history, the most important factor related to IgG seropositivity was age; the rate was 81% in cases younger than 34 y old, while it was 29% in cases older than 34 y. CONCLUSIONS: This study indicates that people suffering from the disease did not ask for any professional healthcare or that the healthcare providers could not diagnose these cases.

The effectiveness of therapeutic ultrasound to the mechanically damaged chondrocyte culture.

OBJECTIVE: This study aimed to evaluate the efficacy of low intensity (0.1-0.8 Watt/cm2) pulsed ultrasound on chondrocyte cell proliferation and migration. METHODS: Low-intensity pulsed ultrasound (frequency 3 MHz, duty cycle 25%, and pulse repetition frequency 150 Hz) for 5 minutes at different spatial average intensities was applied on chondrocyte cells. First, the optimum dose with significantly increased proliferation was determined to be 0.5 W/cm2 for 5 minutes of duration. Then, 0.5 W/cm2 ultrasound intensity was applied for durations of 2.5, 5, 7.5, and 10 minutes, and healing was assessed by monitoring cell migration and proliferation. RESULTS: At the intensity of 0.5 W/cm2 48 hours after the application, a statistically significant increase in proliferation (p = .0089) was observed in chondrocyte cells compared to the control group. Proliferation was analyzed at 4, 8, 24, and 48 hours after applying 0.5 W/cm2 ultrasound for durations of 2.5, 5, 7.5, and 10 minutes. Statistically significant increases were observed at 4 hours (p = .009), 8 hours (p = .032), 24 hours (p = .0084), and 48 hours (p = .00098) with 10 minutes of exposure. For 7.5 min of exposure duration, significant increases were observed at 48 hours (p = .045). In migration for all parameters, no statistically significant improvement (p > .05) was observed. CONCLUSION: It was shown that low intensity pulsed ultrasound induces cartilage cell proliferation; therefore, it may have a disease-modifying effect in the treatment of osteoarthritis. However, no positive effect was observed on cartilage cell migration.

Green staining of clothing: a signal for pseudomonal infection.

Anticonvulsant hypersensitivity syndrome (AHS) is a nondose-related idiosyncratic reaction to aromatic antiepileptic drugs and is a cause of drug discontinuation. Pseudomonas aeruginosa is a gram-negative bacillus that can produce infections in many different organs, including the skin and soft tissue. We report a patient with erythroderma and AHS who developed a pseudomonal infection. Green staining of the underwear served as a diagnostic clue for severe P aeruginosa infection that had developed because of a local flexural skin infection that spread due to a damaged skin barrier. Inspection of the patient's clothes may give information about any exudate from the skin and should be done routinely as part of the physical examination.

Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic.

BACKGROUND: Created a model in the rats, to prevent mucosal damage and related effects in the patients, who were operated due to mechanical obstruction. Some groups fed fodder with probiotics, some groups fed with standard fodder. It is objected that the damage of gut mucosa and related effects on how to expose the differences of the groups. METHODS: In this study, 48 female Wistar-albino type rats are separated into five groups randomly. In the first operation, rats' terminal ileum was tied up with silk except for the control group. Two groups 24, the other two groups 48 hours later operated again and terminal ileum obstructions were removed. During that time, each one of those 24 and 48 hours of obstructed groups were fed with probiotic. Twenty-four hours later, the control group and other groups were operated for the third time for sampling. Terminal ileum, liver, spleen, MLN (Mesenteric lymph node) and blood samples were taken. RESULTS: The research group, which was obstructed and fed with probiotics during 48 hours, was significantly observed in increased mucosa cell loss and mucosal edema. Bacterial translocation was found more common in groups without probiotics. Tissue GR (Glutathione reductase) and erythrocyte CAT (Catalase) were lower in the group of 24 hours obstructed and given probiotics. CONCLUSION: The findings suggest that the high rate of mucosal edemas in the groups that are fed with probiotics can be seen as damage, but we think that probiotics are consonant with the strength of the mucosal barrier. Thus, in the groups fed with probiotics, it is possible that bacterial translocation is seen less, and some antioxidative enzymes are found less. Further studies are needed to investigate the benefits of probiotics in patients operated for obstruction.

The diagnosis of diabetic foot osteomyelitis: examination findings and laboratory values.

BACKGROUND: This study aimed to demonstrate how much examination findings and laboratory values can be helpful in the diagnosis of osteomyelitis in patients with diabetic foot infections. MATERIAL/METHODS: Data of 46 consecutive inpatients prospectively followed up according to a specially designed "Diabetic Foot Follow-up Form" were analyzed. Following diagnostic interventions, clinical and laboratory findings of patients with and without a diagnosis of osteomyelitis were compared. In these patients with and without osteomyelitis confirmed by histopathology and/or microbiology and/or MRI the sensitivity and specificity of ESR (erythrocyte sedimentation rate) and wound size were also determined. RESULTS: There was no significant differences in the duration of diabetes or the existence of nephropathy or vascular disease, while the other findings (ESR, C-reactive protein, wound size, history of diabetic foot ulcer, and retinopathy) were significantly different. It is found that ESR > or =65 mm/h together with a wound size > or =2 cm2 had a sensitivity of 83%, specificity of 77%, positive predictive value of 80%, and negative predictive value of 81% in the diagnosis of osteomyelitis. CONCLUSIONS: This study demonstrated that simple clinical evaluation and laboratory findings without using expensive imaging methods may be important indicators of osteomyelitis.

Invasive fungal granuloma of the brain caused by Aspergillus fumigatus: a case report and review of the literature.

BACKGROUND: Involvement of the brain by Aspergillus fumigatus, named as invasive aspergillosis, is extremely rare. Definitive diagnosis needs isolation of the fungus from the tissue specimens and its culture. The disease is very resistant to treatment and quickly becomes fatal despite antifungal chemotherapy with AmB preparations, the drugs of choice for the infection. CASE DESCRIPTION: We hereby present a unique case of fungal granuloma of the brain due to A fumigatus, which was cured successfully by intensive antifungal treatment, along with a brief literature review. CONCLUSIONS: Although it is rare, we draw the attention to the fact that early diagnostic procedures with rapid confirmation of Aspergillus infection and an early initiation of therapy are pivotal for a benign clinical course in such cases. A complete regression of the disease could be achieved with medical therapy alone with conventional AmB or liposomal AmB combined with oral itraconazole even if a total surgical excision of the lesions could not be performed in complicated cases, as in our patient.

Risk Factors for Infection with Pseudomonas aeruginosa in Diabetic Foot Infections.

BACKGROUND: Selecting empirical therapy for a diabetic foot infection (DFI) requires knowing how likely infection with Pseudomonas aeruginosa is in a particular patient. We designed this study to define the risk factors associated with P aeruginosa in DFI. METHODS: We performed a preplanned microbiological subanalysis of data from a study assessing the effects of treatment with intralesional epidermal growth factor for diabetic foot wounds in patients in Turkey between January 1, 2012, and December 31, 2013. Patients were screened for risk factors, and the data of enrolled individuals were recorded in custom-designed patient data forms. Factors affecting P aeruginosa isolation were evaluated by univariate and multivariate logistic regression analyses, with statistical significance set at P < .05. RESULTS: There were 174 patients enrolled in the main study. Statistical analysis was performed in 90 evaluable patients for whom we had microbiological assessments. Cultures were sterile in 19 patients, and 89 bacterial isolates were found in the other 71. The most frequently isolated bacteria were P aeruginosa (n = 23, 25.8%) and Staphylococcus aureus (n = 12, 13.5%). Previous lower-extremity amputation and a history of using active wound dressings were the only statistically significant independent risk factors for the isolation of P aeruginosa in these DFIs. CONCLUSIONS: This retrospective study provides some information on risk factors for infection with this difficult pathogen in patients with DFI. We need prospective studies in various parts of the world to better define this issue.

Neuraminidase decreases in vitro adherence of slime-forming coagulase-negative staphylococci to biosynthetic ovine collagen vascular graft.

Vascular prosthetic graft infection is a major complication of vascular surgery that starts with adhesion of the microorganism to the graft. Because slime-forming microorganisms are the major causative agents in graft infection, the goals of investigators in this study were (1) to investigate the bacterial adherence of slime-forming and non-slime-forming coagulase-negative staphylococci (CNS), and (2) to determine the role of neuraminidase (NANase) in bacterial adherence to the biosynthetic ovine collagen graft. Human plasma was instilled and incubated at 37 degrees C in preparation for fibrin deposition of grafts. After 48 hours, incubation grafts were drained and inoculated with slime-forming and non-slime-forming CNS in tryptic soy broth in the presence and in the absence of neuraminidase. After 24 hours of incubation at 36 degrees C, grafts were vortexed and cultured for colony count. Bacterial counts were expressed as total colony-forming units per longitudinal centimeter of the graft. Slime-forming CNS had greater affinity to the collagen graft compared with non-slime-forming CNS (P<.05). Adherence of slime-forming CNS was impaired by NANase treatment (P<.001). NANase treatment of patients with non-slime-forming CNS did not change adherence to the graft (P>.05). Results show that slime plays an important role in the pathogenesis of vascular graft infection. Adherence of slime-forming CNS can be decreased through the administration of NANase. This may have implications for the development of neuraminidase-embedded vascular grafts designed to reduce the occurrence of biomaterial-related infection.

Hepatitis A and B seropositivity among medical students.

OBJECTIVE: Health science students are commonly exposed to some infectious agents, including hepatitis A virus (HAV) and hepatitis B virus (HBV), which may cause substantial morbidity and even deaths. The identification of prevalence and risk factors is essential for implementing efficacious preventive measures. A serological survey was performed among medical students of Adnan Menderes University Medical Faculty to determine the prevalence of antibodies against HAV and HBV, and, as a secondary objective, to determine risk factors for acquisition of these infections. METHODS: Nearly all students were included in the study. All participants completed a structured questionnaire that assessed demographic and socio-economic characteristics. Anti-HAV IgG, anti-HBc IgG, HbsAg and anti-HBs were tested using commercially available Elisa kits. RESULTS: A total of 247 students, 146 (59.1%) male and 101 (40.9%) female, were included in the study. The prevalence of anti-HAV IgG was detected as 64%. Number of siblings and place of residence were detected as independent factors affecting the anti-HAV seropositivity. The prevalence of anti-HBc IgG was detected as 7.3%. Among the students positive for anti-HBc IgG, 5 (2%) students were HBsAg positive and the other 13 (5.3%) were anti-HBs positive. HBV infection in household members, risky sexual behaviour and vaccination were independent factors affecting the prevalence of anti-HBc IgG positivity. CONCLUSIONS: The high susceptibility of medical students and their increased risk of clinical HAV and HBV infection identify a need for primary prevention through the administration of vaccination in this group in western Turkey.

Comparison of different doses of vancomycin andteicoplanin lock solutions in catheters colonized with Staphylococcus epidermidis: An in vitro, blinded, antibiotic lock study.

BACKGROUND: The antibiotic lock (AL) technique is used for sterilization ofthe intraluminal surface of catheters. This technique consists of filling a catheter lumen with an antibiotic solution and allowing it to dwell for a time sufficient to sterilize the device. Glycopeptide antibiotics (vancomycin and teicoplanin) are commonly used agents for this purpose. But studies evaluating the different dosages of these antibiotics, their optimum concentrations, and duration in AL treatment are lacking. OBJECTIVE: The aim of this study was to compare the efficacy of differentdoses of vancomycin/saline solution (VSS) and teicoplanin/saline solution (TSS) and to establish the optimal dosage and time needed to eliminate intraluminal methicillin-resistant Staphylococcus epidermidis colonization. METHODS: This in vitro AL study was conducted at the Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University Medical Faculty, Aydin, Turkey. Catheters were divided into 2 groups those colonized with slime-forming S epidermidis, and those colonized with non-slime-forming S epidermidis. In each group, catheters were locked with VSS or TSS at 1-, 3-, and 5-mg/mL doses. Catheters instilled with saline solution were used as the control group. After 12 hours of incubation, the catheters were drained and filled with human plasma. Instillation of human plasma or AL solution was alternated every 12 hours to simulate clinical conditions. Every other day, catheters locked with each antibiotic dose or saline were cultured to determine colony count. These procedures were maintained until the catheters were sterile. RESULTS: The baseline counts of slime-forming and non-slime-forming S epidermidisadhered to 1-cm segment catheters were 39 × 106 and 32 × 106 colony-forming units, respectively. The bacterial count was decreased significantly from baseline on the first day after the start of treatment (day 1) (P < 0.001). At the end of day 7, all catheters treated with antibiotics were sterile. The de creases in bacterial count were statistically similar in catheters treated with all doses of VSS and TSS. Also, the decrease in intraluminal colonization was statistically similar in catheters colonized with slime-forming S epidermidis and non-slime-forming S epidermidis. CONCLUSION: In this in vitro, blinded AL study, the efficacy of vancomycin and teicoplanin lock solutions were similar and sterilized the catheters in 7 days, suggesting that the 2 antibiotics might be selected for shorter durations compared with those currently recommended for AL treatment in catheter-related infections due to methicillin-resistant staphylococci.

Escherichia coli bind to urinary bladder epithelium through nonspecific sialic acid mediated adherence.

The first step in the bacterial colonization and infection of uropathogenic Escherichia coli is adherence to uroepithelium. Over 80% of all urinary tract infections are caused by E. coli. Uropathogenic E. coli express several adherence factors including type 1 and P fimbriae, which mediate attachment to the uroepithelium through specific binding to different glycoconjugate receptors. We showed that P and type 1 fimbriae are not the sole adhesins on uropathogenic E. coli and sialic acid also mediates nonspecific bacterial adherence of uropathogenic E. coli and urinary bladder epithelium.

Neuraminidase produces dose-dependent decrease of slime production and adherence of slime-forming, coagulase-negative staphylococci.

BACKGROUND: Slime is one of the important structures of certain bacterial strains involved in nonspecific adherence. This study was conducted to determine the role of neuraminidase on slime formation and adherence of slime-forming coagulase-negative staphylococci to inert surface. METHODS: Quantitative biofilm and qualitative bacterial adherence assays were performed with increasing concentrations of neuraminidase extracted from Clostridium perfringens-treated bacteria in polystyrene plates and polypropylene tubes. RESULTS: Slime production of slime-forming, coagulase-negative staphylococci was significantly decreased dose dependently at > or =100 mU/mL (p <0.001). Bacterial adherence to smooth surface was impeded at > or =100 mU/mL of neuraminidase treatment and adherence results were comparable with slime production assay results. CONCLUSIONS: Sialic acid may be a constituent molecule of slime and involved in bacterial adherence to inert surface. These results represent new insight into the mechanism of slime production and adherence of slime-forming, coagulase-negative staphylococci to inert surface.

Effect of preventive applications on prevalence of hepatitis B virus and hepatitis C virus infections in West Turkey.

OBJECTIVE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are community health problems in developing countries and the most common causative agents of chronic hepatitis, cirrhosis and hepatocellular carcinoma. This study investigates the prevalence and the effect of preventive applications on prevalence of HBV and HCV infections in blood donors. METHODS: Blood donors enrolled to the University and State Hospital Blood Banks in Aydin region of Turkey through the years 1993 to 2002 were retrospectively analyzed. Blood donors were investigated in 2 groups, Group I (1993-1997) and Group II (1998-2002) to compare the prevalence difference in 10-years period. Serum hepatitis B antigen (HbsAg) and anti-HCV were tested by commercially available enzyme-linked immunosorbent assay kits and anti-HCV positive results were confirmed by recombinant immune blot assays HCV test. RESULTS: The prevalence of HBV and HCV infections was determined as 1.5% and 0.19% over the period 1993-2002. Although, the prevalence of HBV infection declined significantly in Group II (1.17%) in comparison with Group I (2.27%) (p<0.0001), there was no significant difference in both groups regarding HCV infection (p=0.238). CONCLUSION: Preventive applications against blood transfusion related diseases succeed to decrease HBV infection significantly in West Turkey. Vaccination seems to be the most effective method to prevent hepatitis infection.

Saccharomyces boulardii expresses neuraminidase activity selective for α2,3-linked sialic acid that decreases Helicobacter pylori adhesion to host cells.

Helicobacter pylori is a major causative agent of gastritis and peptic ulcer disease and is an established risk factor for gastric malignancy. Antibiotic combination therapy can eradicate H. pylori. As these same regimens can evoke adverse effects and resistance, new alternative therapies or adjunctive treatments are needed. A probiotic approach may provide a novel strategy for H. pylori treatment. In the current study, two probiotic bacteria, Lactobacillus acidophilus and Lactobacillus reuteri, and a probiotic yeast, Saccharomyces boulardii, were evaluated for their ability to influence H. pylori viability, adherence to gastric and duodenal cells, as well as the effect of S. boulardii on cell surface expression of sialic acid. Our results indicate that S. boulardii contains neuraminidase activity selective for α(2-3)-linked sialic acid. This neuraminidase activity removes surface α(2-3)-linked sialic acid, the ligand for the sialic acid-binding H. pylori adhesin, which in turn, inhibits H. pylori adherence to duodenal epithelial cells.

Hypochlorous Acid: an ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency.

INTRODUCTION: Chronic wounds and the infections associated with them are responsible for a considerable escalation in morbidity and the cost of health care. Infection and cellular activation and the relation between cells are 2 critical factors in wound healing. Since chronic wounds offer ideal conditions for infection and biofilm production, good wound care strategies are critical for wound healing. Topical antiseptics in chronic wounds remain in widespread use today. These antiseptics are successful in microbial eradication, but their cytotoxcity is a controversial issue in wound healing. OBJECTIVE: The aim of this study was to investigate the effect of stabilized hypochlorous acid solution (HOCl) on killing rate, biofilm formation, antimicrobial activity within biofilm against frequently isolated microorganisms and migration rate of wounded fibroblasts and keratinocytes. MATERIALS AND METHODS: Minimal bactericidal concentration of stabilized HOCl solution for all standard microorganisms was 1/64 dilution and for clinical isolates it ranged from 1/32 to 1/64 dilutions. RESULTS: All microorganisms were killed within 0 minutes and accurate killing time was 12 seconds. The effective dose for biofilm impairment for standard microorganisms and clinical isolates ranged from 1/32 to 1/16. Microbicidal effects within the biofilm and antibiofilm concentration was the same for each microorganism. CONCLUSION: The stabilized HOCl solution had dose-dependent favorable effects on fibroblast and keratinocyte migration compared to povidone iodine and media alone. These features lead to a stabilized HOCl solution as an ideal wound care agent.

Investigation of therapeutic efficiency of bleomycin and bleomycin-glucuronide labeled with (131)I on the cancer cell lines.

The aim of this study is to determine the incorporations of radiolabeled bleomycin ((131)I-BLM) and bleomycin-glucuronide ((131)I-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with (131)I, quality control studies were done and the incorporation yields of (131)I-BLM and (131)I-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for (131)I-BLM and (131)I-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that (131)I-BLM and (131)I-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of (131)I-BLMGLU was higher than that (131)I-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of (131)I-BLMGLU on the four cell lines were about five to six times higher than (131)I-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the ß-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells.

Radiolabeling of bleomycin-glucuronide with (131)I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice.

Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.