Preventive Risk Assessment of Medication in Intensive Wards.

Background: Failure mode and effect analysis (FEMA) approach as one of the preventive risk management strategies to identify and prevent errors in the medication process in nursing care in the 10 intensive wards in two large hospitals in Khorramabad. Methods: This study is applied descriptive research, which is conducted as a mixed-method quantitative-qualitative approach using focus group discussion. Results: The average risk priority number (RPN) score for the intensive care unit (ICU) in this study was 20.97. The highest RPN scores were associated with the SICU (Surgical ICU) and EICU (Emergency ICU) wards with RPN of 24.66 and 22.71, respectively. Among the steps of the medication process, the first step "physician order" had the highest score (RPN = 26.08). Conclusions: The intensive wards, which had high RPN scores are exposed to more risk of the drug medication process like EICU and SICU; also, simple acts such as handwriting readable by a physician can considerably reduce risk in the ICU.

Post-antifungal effect of the combination of anidulafungin with amphotericin B and fluconazole against fluconazole-susceptible and -resistant Candida albicans.

Background and Purpose: Invasive candidiasis is a life-threatening condition that kills a large number of immunocompromised patients each year worldwide. We used post-antifungal effect studies to analyze the activities of anidulafungin (AFG), as a clinically crucial antifungal drug, amphotericin B (AMB), and fluconazole (alone and in combinations) against FLC-susceptible and -resistant Candida albicans (C. albicans) isolates obtained from the cancer patients. Materials and Methods: We tested the phenomenon of post antifungal effects of FLC, AMB, AFG, and combinations of FLC+AFG, AFG+AMB, and FLC+AMB against 17 C. albicans isolates obtained from the oral cavity of cancer patients. Isolates that had not been exposed to antifungals, served as a control group. Colony counts were performed at 0, 2, 4, 6, and 24 h after a brief (1 h) exposure to antifungal. Results: The FLC had no detectable post-antifungal effect independent of antifungal concentration and resembled drug-free FLC (control). Significant variations in the post-antifungal effect were observed when all AMB and AFG were compared to FLC. The combination of AFG and AMB with FLC resulted in effective activity compared to FLC alone. Combination regimens were rated as indifferent in general. Interestingly, low dosages of the AFG displayed increasing fungistatic action as it approached a fungistatic endpoint against C. albicans isolates (n=17). Conclusion: Our findings suggested that brief exposure to AFG, in combination with FLC and AMB, at low concentrations of the medicines utilized, could be effective in the evaluation and optimization of new dosage regimens to manage candidiasis. However, future studies will determine the clinical utility of our findings.

Radiolabeled nanobodies for tumor targeting: From bioengineering to imaging and therapy.

So far, numerous molecules and biomolecules have been evaluated for tumor targeting purposes for radionuclide-based imaging and therapy modalities. Due to the high affinity and specificity against tumor antigens, monoclonal antibodies are appropriate candidates for tumor targeting. However, their large size prevents their comprehensive application in radionuclide-based tumor imaging or therapy, since it leads to their low tumor penetration, low blood clearance, and thus inappropriate tumor-to-background ratio. Nowadays, the variable domain of heavy-chain antibodies from the Camelidae family, known as nanobodies (Nbs), turn into exciting candidates for medical research. Considering several innate advantages of these new tumor-targeting agents, including excellent affinity and specificity toward antigen, high solubility, high stability, fast washout from blood, convenient production, ease of selection, and low immunogenicity, it assumes that they may overcome generic problems of monoclonal antibodies, their fragments, and other vectors used for tumor imaging/therapy. After three decades of Nbs discovery, the increasing number of their preclinical and clinical investigations, which have led to outstanding results, confirm their application for tumor targeting purposes. This review describes Nbs characteristics, the diagnostic and therapeutic application of their radioconjugates, and their recent advances.

In vitro and in silico evaluation of P-glycoprotein inhibition through 99m Tc-methoxyisobutylisonitrile uptake.

P-glycoprotein (P-gp) is a multidrug resistance (MDR) transporter with unknown structural details. This macromolecule is normally responsible for extruding xenobiotics from normal cells. Overexpression of P-gp in tumor cells is a major obstacle in cancer chemotherapy. In this study, human 3D model of P-gp was built by homology modeling based on mouse P-gp crystallographic structure and stabilized through 1 ns molecular dynamics (MD) simulation. Stabilized human P-gp structure was used for flexible docking of 80 drugs into the putative active site of P-gp. Accordingly, digoxin, itraconazole, risperidone, ketoconazole, prazosin, verapamil, cyclosporine A, and ranitidine were selected for further in vitro assay. Subsequently, cell-based P-gp inhibition assay was performed on Caco-2 cells while 99m Tc-methoxyisobutylisonitrile (MIBI) was used as a P-gp efflux substrate for calculating IC50 values. Results of the 99m Tc-MIBI uptake in drug-treated Caco-2 cells were in agreement with the previously reported activities. This study for the first time described the relation between molecular dynamics and flexible docking with cellular experiments using 99m Tc-MIBI radiotracer for evaluation of potencies of P-gp inhibitors. Finally, results showed that our radiotracer-cell-based assay is an accurate and fast screening tool for detecting P-gp inhibitors and non-inhibitors in drug development process.

99m Tc-anti-epidermal growth factor receptor nanobody for tumor imaging.

Nanobodies are important biomolecules for tumor targeting. In this study, we synthesized and labeled anti-epidermal growth factor receptor (EGFR) nanobody OA-cb6 with 99m Tc(CO)3+ and evaluated its characteristics for targeting the EGFR in the A431 human epidermal carcinoma cell line. Nanobody radiolabeling was achieved with high yield and radiochemical purity, and the radioconjugate was stable. Biodistribution results in nude mice exhibited a favorable tumor-to-muscle ratio at 4-hr postinjection, and tumor location was visualized at 4 hr after injection of radiolabeled nanobody. Our result showed that the OA-cb6-99m Tc-tricarbonyl radiolabeled nanobody is a promising radiolabeled biomolecule for tumor imaging in cancers with high EGFR overexpression.

The Past, Current Studies and Future of Organometallic 99mTc(CO)3 Labeled Peptides and Proteins.

The labeling of biomolecule using 99mTc-tricarbonyl is an interesting tool for the diagnosis of diseases. This labeling startegy has several advantages as compared to other common radiolabeling techniques. This review is a complete overview of synthesis and chemistry of 99mTc-tricarbonyl molecule for labeling peptides and proteins. Also, the effect of ligand type on the stability and in vivo biodistribution of ;99m;Tc-tricarbonyl labeled biomolecules are discussed. Chemistries of cyclopentadienyl and hexa histidine tag as two important bifunctional chelating agents (BFCA) are presented. The in vitro and in vivo behaviors of some 99mTc-tricarbonyl labeled peptides and proteins are explained. Preclinical outcomes revealed that these labeled compounds are biologically, kinetically and thermodynamically stable. Findings showed that 99mTc-tricarbonyl labeled biomolecules are promising tools for future clinical applications in image diagnosis.

Tumor targeting with a (99m)Tc-labeled AS1411 aptamer in prostate tumor cells.

AS1411, a 26-base guanine-rich oligonucleotide aptamer, has high affinity to nucleolin, mainly on tumor cell surfaces. In this study, a modified AS1411 was labeled with (99m)Tc and evaluated as a potential tumor-targeting agent for imaging. The AS1411 aptamer was conjugated with HYNIC and labeled with (99m)Tc in the presence a co-ligand. Radiochemical purity and stability testing of the (99m)Tc-HYNIC-AS1411 aptamer were carried out with thin layer chromatography and a size-exclusion column in normal saline and human serum. Cellular nucleolin-specific binding, cellular internalization in DU-145 cells, as high levels of nucleolin expression, were performed. Additionally, biodistribution in normal mice and DU-145 tumour-bearing mice was assessed. Radiolabeling of the aptamer resulted in a reasonable yield and radiochemical purity after purification. The aptamer was stable in normal saline and human serum, and cellular experiments demonstrated specific binding of the AS1411 aptamer to the nucleolin protein. Based on biodistribution assessment of (99m)Tc-HYNIC-AS1411, rapid blood clearance was seen after injection and it appears that the excretion route was via the urinary system at 1 h post-injection. Tumours also showed a higher accumulation of radioactivity with this labeled aptamer. (99m)Tc-AS1411 can be a potential tool for the molecular imaging of nucleolin-overexpressing cancers.