Indigo Carmine: Between Necessity and Concern.

Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although indigo carmine is considered toxic and has many adverse effects, it is found in many foods, and the maximum permitted level is 500 mg/kg. Indigo carmine is one of the most used dyes in the textile industry, especially for dyeing denim, and it is also used in medicine due to its impressive applicability in diagnostic methods and surgical procedures, such as in gynecological and urological surgeries and microsurgery. It is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine; its use in various industries and medicine; the adverse effects of its ingestion, injection, or skin contact; the effects on environmental pollution; and its toxicity testing. For this review, 147 studies were considered relevant. Most of the cited articles were those about environmental pollution with indigo carmine (51), uses of indigo carmine in medicine (45), and indigo carmine as a food additive (17).

Molecularly Imprinted Carriers for Diagnostics and Therapy-A Critical Appraisal.

Simultaneous diagnostics and targeted therapy provide a theranostic approach, an instrument of personalized medicine-one of the most-promising trends in current medicine. Except for the appropriate drug used during the treatment, a strong focus is put on the development of effective drug carriers. Among the various materials applied in the production of drug carriers, molecularly imprinted polymers (MIPs) are one of the candidates with great potential for use in theranostics. MIP properties such as chemical and thermal stability, together with capability to integrate with other materials are important in the case of diagnostics and therapy. Moreover, the MIP specificity, which is important for targeted drug delivery and bioimaging of particular cells, is a result of the preparation process, conducted in the presence of the template molecule, which often is the same as the target compound. This review focused on the application of MIPs in theranostics. As a an introduction, the current trends in theranostics are described prior to the characterization of the concept of molecular imprinting technology. Next, a detailed discussion of the construction strategies of MIPs for diagnostics and therapy according to targeting and theranostic approaches is provided. Finally, frontiers and future prospects are presented, stating the direction for further development of this class of materials.

Comparative Evaluation of 99mTc-Octreotide for Diagnostic Accuracy Assessment and Localization of 177Lu-DOTA-TATE in Neuroendocrine Tumors.

INTRODUCTION: Neuroendocrine tumors, due to uncommon and multi-centric origin, pose a clinical challenge for their diagnosis and treatment. Developing countries where Ga-68 DOTA-TOC/NOC PET imaging is very limited and costly, 99mTc based SSR imaging can be used as the key tool for its diagnosis and assessment of therapy response. Hence we used two different 99mTc-radiopharmaceuticals for NET imaging designated as RP-1 and RP-2 for clinical assessment and peptide receptor therapy response of 177Lu-DOTA-TATE by manually synthesized acetate buffer. 99mTc- labeled RP-1 and RP-2 sensitivity, specificity; positive and negative predictive values were calculated and compared by SPECT/CT images for utilization in peptide receptor radionuclide therapy (PRRT). METHOD: Sodium-pertechnetate was used for labeling both radiopharmaceuticals, while 177Lu nca (0.04 N HCl) DOTA-TATE was synthesized by 0.1M ammonium acetate/ascorbic acid. 75 patients of known primary NET imaging with RP-1 and RP-2 were evaluated for SRR avidity and 3 were selected for PRRT. All images were correlated with 68Ga-DOTA-TOC scan, histopathology, CT and/or MRI reports. RESULTS: Out of 75 patients, the somatostatin receptor imaging of 39 patients of neuro-endocrine was performed with RP-1, found 23 as true positive, 7 as true negative with sensitivity, specificity, PPV and NPV of 71.87%, 100%, 100% and 43.75%, whereas 36 images with RP-2 calculated 22 T/P, 6 as T/N, 8 as F/N, with 75.8%, 100%, 100% and 50% respectively. Their 177Lu-DOTA-TATE SPECT/CT revealed specific localization of therapeutic radionuclide. CONCLUSION: 99mTc-imaging of RP-2, as compared to RP-1, had better efficiency and sensitivity and could effectively be used as an alternative to Ga-68 DOTA/TOC PET imaging and Lu-177 DOTA-TATE PRRT therapy response evaluation.

Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues.

We are investigating an imaging agent for early detection of colorectal cancer. The agent, named the nanobeacon, is coumarin 6-encapsulated polystyrene nanospheres whose surfaces are covered with poly(N-vinylacetamide) and peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal sugars of the Thomsen-Friedenreich antigen, which is expressed cancer-specifically on the mucosa, respectively. We expect that cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. In the present study, biopsied human tissues were used to evaluate the potential use of the nanobeacon in the clinic. Prior to the clinical study, diagnostic capabilities of the nanobeacon for detection of colorectal cancer were validated using 20 production batches whose characteristics were fine-tuned chemically for the purpose. Ex vivo imaging studies on 66 normal and 69 cancer tissues removed from the colons of normal and orthotopic mouse models of human colorectal cancer, respectively, demonstrated that the nanobeacon detected colorectal cancer with excellent capabilities whose rates of true and false positives were 91% and 5%, respectively. In the clinical study, normal and tumor tissues on the large intestinal mucosa were biopsied endoscopically from 11 patients with colorectal tumors. Histological evaluation revealed that 9 patients suffered from cancer and the rest had adenoma. Mean fluorescence intensities of tumor tissues treated with the nanobeacon were significantly higher than those of the corresponding normal tissues. Correlation of magnitude relation of the intensity in individuals was observed in cancer patients with a high probability (89%); however, the probability reduced to 50% in adenoma patients. There was a reasonable likelihood for diagnosis of colorectal cancer by the nanobeacon applied to the mucosa of the large intestine.

Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications.

Dendrimers are large polymeric structures with nanosize dimensions (1-10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific "architecture" and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases.

Visualizing nucleic acid metabolism using non-natural nucleosides and nucleotide analogs.

Nucleosides and their corresponding mono-, di-, and triphosphates play important roles in maintaining cellular homeostasis. In addition, perturbations in this homeostasis can result in dysfunctional cellular processes that cause pathological conditions such as cancer and autoimmune diseases. This review article discusses contemporary research areas applying nucleoside analogs to probe the mechanistic details underlying the complexities of nucleoside metabolism at the molecular and cellular levels. The first area describes classic and contemporary approaches used to quantify the activity of nucleoside transporters, an important class of membrane proteins that mediate the influx and efflux of nucleosides and nucleobases. A focal point of this section is describing how biophotonic nucleosides are replacing conventional assays employing radiolabeled substrates to study the mechanism of these proteins. The second section describes approaches to understand the utilization of nucleoside triphosphates by cellular DNA polymerases during DNA synthesis. Emphasis here is placed on describing how novel nucleoside analogs such as 5-ethynyl-2'-deoxyuridine are being used to quantify DNA synthesis during normal replication as well as during the replication of damaged DNA. In both sections, seminal research articles relevant to these areas are described to highlight how these novel probes are improving our understanding of these biological processes. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions.

Thioaptamers targeting dengue virus type-2 envelope protein domain III.

Thioaptamers targeting the dengue-2 virus (DENV-2) envelope protein domain III (EDIII) were developed. EDIII, which contains epitopes for binding neutralizing antibodies, is the putative host-receptor binding domain and is thus an attractive target for development of vaccines, anti-viral therapeutic and diagnostic agents. Thioaptamer DENTA-1 bound to DENV-2 EDIII adjacent to a known neutralizing antibody binding site with a dissociation constant of 154nM.

Synthesis and biological evaluation of newly designed phosphonate based bone-seeking agent.

A cyclic tetraaza based bifunctional triphosphonate ligand 10-(2-aminoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris(methylenephosphonic acid) (DO3MP-EA) was synthesized as bone-seeking theranostic agent. The compound was characterized by spectroscopic techniques and labelled with (99m)Tc with more than 97% purity. Blood clearance of 99mTc labelled compound a quick wash out from the circulation. The compound was excreted mainly via kidneys and accumulation of (99m)Tc-DO3MP-EA in bone was 9.53 ± 1.06% of injected dose per gram of bone at 1 h. The preliminary CADD analysis confirms the efficacy of DO3MP-EA (G Score -7.005) as better binding agent for osteocalcin (pdb 1Q8H) rather than other known clinical agents. Subsequently stability constant of chelate with Ga(III) was found to be 18.6 which confirms its efficacy as (68)Ga labelled PET radiopharmaceutical for bone.

Detection of serum specific IgE to crab allergen in different group people with extracted Eriocheir sinensis allergens / 中国生化药物杂志

Purpose To detect serum specific IgE to crab allergen in different group people with extracted Eriocheir sinensis allergic proteins and to provide laboratorial evaluation for diagnosis and treatment of crab anaphylaxis.Methods Micro titer plates were coated with the allergic proteins extracted from crab.A total of 1907 serum samples from 3 group people were detected for specific IgE to crab allergens with indirect ELISA.The serological IgE level of different group people allergic to crab food wag compared and analyzed.Results 203 individuals were serum specific IgE positive in the detected 1 907 serum samples,and the positire rates Wag 10.65 percent(203/1 907).The statistical analysis showed that the difference of serum IgE positire rates among the 3 group people wag very significant(P＜0.01).Conclusion The detection of serum specific IgE using allergic proteins extracted from crab has diagnostic meaning,since it can be used as laboratorial evaluation for clinical diagnosis and treatment of crab anaphylaxis.

Susceptible, intermediate, and resistant - the intensity of antibiotic action.

INTRODUCTION: To date, the resistance of infectious agents has been assessed by widely varying criteria in different countries. Therefore, published data on resistance often cannot be meaningfully compared. In Germany, different laboratories can potentially report different results for identical microorganisms, since there is no uniform system for categorization. This situation is unsatisfactory. METHODS: Selective literature review and evaluation of committee reports. RESULTS: The new ISO standard 20776 for determination of the resistance of infectious agents and the harmonized evaluation system of the European Society for Clinical Microbiology and Infectious Diseases provide a new basis for susceptibility testing. The categorization of infectious agents as "susceptible," "intermediate," or "resistant" to particular antibiotics will become more reliable and will be consistent throughout Europe. DISCUSSION: For a number of antibiotics, the criteria for evaluation of infectious agents as "susceptible," "intermediate", or "resistant" will change. Comparability with earlier resistance data will be compromised. However, the new evaluation criteria reflect current knowledge on the pharmacokinetics and pharmacodynamics of antimicrobial substances.