Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis

Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.

TOXICITY ANALYSIS OF RGD-CHITOSAN FROM SHRIMP SHELL SCAFFOLD MEMBRANES TOWARD HUMAN DENTAL PULP CELLS

Objective: This study aimed to analyze RGD-Chitosan from Shrimp Shells’ Scaffolds’ (RCSSS) and CSSS membrane toxicity toward human dental pulpcells.Methods: Human dental pulp cells were cultured for 5 days and then exposed to RCSSS or CSSS membranes for 24 hrs. Cell viability was determinedusing an MTT assay method.Results: Cell viability of the RCSSS group and CSSS group was higher than the cell viability of the control group. The cell viability of the RCSSSgroup 2 mg (537.39%) was significantly higher than the CSSS group 2 mg (301.74%).Conclusions: RCSSS membranes were not toxic toward human dental pulp cells and showed better effect toward human dental pulp cells comparedto CSSS membranes.

Chemoinformatic Investigation of Antibiotic Antagonism: The Interference of Thymus glabrescens Essential Oil Components with the Action of Streptomycin

Given the importance of Thymus glabrescens as a useful antibacterial remedy, we have evaluated the antibacterial and streptomycin-modifying activity of Thymus glabrescens essential oil, geraniol, geranyl acetate and thymol. It was shown that all substance-streptomycin combinations produced predominantly antagonistic interactions. Furthermore, combinations between geraniol and thymol showed dominant additive effect. Chemoinformatics results, combined with experimental data, suggest that antagonistic interactions with streptomycin were not a consequence of the antimicrobial action at the same target, but an outcome of the membrane impairment, followed by the membrane potential/proton motive force dissipation, which decreased the streptomycin uptake. Furthermore, the membrane toxicity of geraniol and thymol was confirmed by their additive antibacterial interactions and parameters of their penetration and accumulation throughout a cell membrane. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

Role of selenium in gastrointestinal inflammatory diseases

The cell-membrane toxicity of reactive oxygen and nitrogen species (RONS) plays an increasing role in the pathomechanism of gastrointestinal tract diseases. Trace elements are important parts of antioxidant protecting system, especially the selenium (Se), which, in the form of glutathione peroxidase contributes to the immunity of the gut (GALT). Due to the absorptional disorders and consequent malnutrition observed in the course of inflammatory bowel diseases (IBD) an important role is associated with nutritional therapy, including energy-, protein- and trace element-support. Human studies show, that IBD is mostly accompanied by lower serum Se concentrations, reduced antoxidant and increased proinflammatory activity. Adequate Se-replacement may reduce the severity of organ failure and infections, but not mortality. However, it is encouraging that in animal studies obvious preventive effect of Se has been found on IBD and chronic inflammation induced colon cancer (CICC). Orv. Hetil., 154 (41), 1636–1640.