The Renal Problems in X-Ray Based Imaging Techniques Using lodinated Radiographic Contrast Agents

Iodinated radiographic contrast agents (IRCA) are pharmaceuticals commonly used for improving the visibility of internal organs and structures in X-ray based imaging techniques such as radiography, angiography and contrast-enhanced computed tomography scans, and for performing cardiac catheterizations and percutaneous coronary interventions. Like all other pharmaceuticals, however, these agents are not completely devoid of risk. The main risk is their nephrotoxicity. Following the description of Contrast-Induced Nephropathy (CIN) and its pathogenesis, the conditions favoring the development of CIN are discussed in depth. The main predisposing condition is a pre-existing renal impairment, particularly when associated with diabetes mellitus. Then, measures to prevent CIN are suggested. The important rules in CIN prevention are: monitoring renal function, discontinuation of potentially nephrotoxic drugs, use of either iodixanol or iopamidol at the lowest dosage possible. Above all, the main procedure for prevention of CIN is an adequate hydration of the patient with either isotonic sodium chloride or sodium bicarbonate solutions

Secondary Metabolites from Plants Inhibiting ABC Transporters and Reversing Resistance of Cancer Cells and Microbes to Cytotoxic and Antimicrobial Agents

Fungal, bacterial, and cancer cells can develop resistance against antifungal, antibacterial, or anticancer agents. Mechanisms of resistance are complex and often multifactorial. Mechanisms include: (1) Activation of ATP-binding cassette (ABC) transporters, such as P-gp, which pump out lipophilic compounds that have entered a cell, (2) Activation of cytochrome p450 oxidases which can oxidize lipophilic agents to make them more hydrophilic and accessible for conjugation reaction with glucuronic acid, sulfate, or amino acids, and (3) Activation of glutathione transferase, which can conjugate xenobiotics. This review summarizes the evidence that secondary metabolites (SM) of plants, such as alkaloids, phenolics, and terpenoids can interfere with ABC transporters in cancer cells, parasites, bacteria, and fungi. Among the active natural products several lipophilic terpenoids [monoterpenes, diterpenes, triterpenes (including saponins), steroids (including cardiac glycosides), and tetraterpenes] but also some alkaloids (isoquinoline, protoberberine, quinoline, indole, monoterpene indole, and steroidal alkaloids) function probably as competitive inhibitors of P-gp, multiple resistance-associated protein 1, and Breast cancer resistance protein in cancer cells, or efflux pumps in bacteria (NorA) and fungi. More polar phenolics (phenolic acids, flavonoids, catechins, chalcones, xanthones, stilbenes, anthocyanins, tannins, anthraquinones, and naphthoquinones) directly inhibit proteins forming several hydrogen and ionic bonds and thus disturbing the 3D structure of the transporters. The natural products may be interesting in medicine or agriculture as they can enhance the activity of active chemotherapeutics or pesticides or even reverse multidrug resistance, at least partially, of adapted and resistant cells. If these SM are applied in combination with a cytotoxic or antimicrobial agent, they may reverse resistance in a synergistic fashion

Preparation and evaluation of tumor-targeting peptide - Oligonucleotide conjugates

Enormous progress has been made in the development of antisense oligodeoxynucleotides (ODNs) as therapeutic agents inhibiting gene expression. Unfortunately, the therapeutical application of ODNs is still held back because of the low cellular uptake and the lack of specific transport into particular cells. In this paper, we report a drug-targeting system using somatostatin receptors (SSTRs) which are overexpressed in various tumors. Phosphorothioate ODNs were covalently linked to Tyr3-octreotate, an analogue of somatostatin. The peptide was assembled by solid-phase synthesis, oxidized to form the cyclic disulfide, and subsequently derivatized with a N-terminal maleimido functionality. 5'-Thiol derivatized phosphorothioate-ODNs directed against the protooncogene bcl-2 were conjugated to this maleimido-modified peptide. Binding studies revealed that the conjugates retain specific binding with nanomolar affinities to SSTRs (IC50-values between 1.83 and 2.52 nM). Furthermore, melting studies with complementary DNA revealed that the terminal conjugation of the ODNs did not significantly affect their hybridization affinity.This project was supported by a grant from the Deutsche Forschungsgemeinschaft (Ei 130/15-3). The authors would like to thank D. Keane and M. Wiersma for skilful assistance in ODN synthesis. Essential support for the establishment of receptor binding assays from Dr. Barbara Stolz, Novartis Pharma AG, Switzerland, is gratefully acknowledged.Peer reviewe

Peptide-PNA conjugates: Targeted transport of antisense therapeutics into tumors

Tumor-specific accumulation of antisense therapeutics: The conjugation of a receptor-binding peptide allows for the first time the selective transport of oligonucleotide analogues into tumor tissue. By using the tert-butyloxycarbonyl (Boc) protecting group stratergy, hybrids of peptide nucleic acids and peptides are accessible that accumulate in tumor tissue at a tenfold higher concentration than the free peptide nucleic acid.Peer reviewe

The potential use of biomarkers in predicting contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect

the choice of the iodinated radiographic contrast media to prevent contrast induced nephropathy

In patients with preexisting renal impairment, particularly those who are diabetic, the iodinated radiographic contrast media may cause contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI), that is, an acute renal failure (ARF), usually nonoliguric and asymptomatic, occurring 24 to 72 hours after their intravascular injection in the absence of an alternative aetiology. Radiographic contrast media have different osmolalities and viscosities. They have also a different nephrotoxicity. In order to prevent CIN, the least nephrotoxic contrast media should be chosen, at the lowest dosage possible. Other prevention measures should include discontinuation of potentially nephrotoxic drugs, adequate hydration with i.v. infusion of either normal saline or bicarbonate solution, and eventually use of antioxidants, such as N-acetylcysteine, and statins

R13. Formulation development of loratadine immediate-release tablets using hot-melt extrusion coupled with 3d-printing technology

Corresponding author (Pharmaceutics and Drug delivery): Sundus Hussain Omari, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1012/thumbnail.jp

Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)

Corresponding author (Pharmaceutics and Drug Delivery): Iman Taha, [email protected]://egrove.olemiss.edu/pharm_annual_posters_2022/1020/thumbnail.jp

the toxicity of iodinated radiographic contrast agents in the clinical practice

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