Multiple organ dysfunction syndrome (MODS) and nosocomial infection following trauma-hemorrhage are among the most important causes of mortality in hemorrhagic shock patients. Dysregulation of the immune system plays a central role in MODS and a fluid having an immunomodulatory effect could be advantageous in hemorrhagic shock resuscitation. Hypertonic saline (HS) is widely used as a resuscitation fluid in trauma-hemorrhagic patients. Besides having beneficial effects on the hemodynamic parameters, HS has modulatory effects on various functions of immune cells such as degranulation, adhesion molecules and cytokines expression, as well as reactive oxygen species production. This article reviews clinical evidence for decreased organ failure and mortality in hemorrhagic shock patients resuscitated with HS. Despite promising results in animal models, results from pre-hospital and emergency department administration in human studies did not show improvement in survival, organ failure, or a reduction in nosocomial infection by HS resuscitation. Further post hoc analysis showed some benefit from HS resuscitation for severely-injured patients, those who received more than ten units of blood by transfusion, patients who underwent surgery, and victims of traumatic brain injury. Several reasons are suggested to explain the differences between clinical and animal models.
Drug‐induced nephrotoxicity is a frequent serious adverse effect, contributing to morbidity and increased healthcare utilization. Prevention or reversal is key. Curcumin has useful biological features that include antioxidant, anti‐inflammatory, and anticancer properties. This review covers aspects of curcumin in relation to prevention of drug‐induced nephrotoxicity: dosage and schedule, effect on kidney biomarkers and histological changes, and mechanisms of curcumin's protective effects. Despite success in some animal models, human studies and clinical administration of curcumin for nephroprotection remains limited due to difficulty in achieving therapeutic levels following oral administration and in determining the optimal dosing schedule. Lack of sufficient evidence from animal studies, coupled with low systemic bioavailability, continues to limit the utilization of curcumin in addressing and controlling drug‐induced nephrotoxicity. Therefore, human studies are required to fully assess and validate the therapeutic potential of curcumin.
The aim of the present study was to improve transfection efficiency using different combinations of cationic liposomes, linear polyethylenimine and DNA. A novel gene delivery system (lipopolyplex) was developed by premixing cationic liposomes containing cholesterol or oligoamine modified cholesterol (derivative I-III) and linear polyethyleneimines (PEIs) following addition of plasmid at three different C/P ratios. The resultant complexes were characterized for their size, zeta potential and ability of DNA condensation. Luciferase reporter gene was used for determination of transfection efficiency in Neuro2A cells. Mean particle size of prepared complexes was less than 200 nm and they showed positive surface charge. The transfection efficiency of vectors was reduced by increasing in carrier concentration/plasmid DNA ratio (C/P ratio) while gene expression of cationic liposome or PEI was increased at higher C/P ratios. Complexes composed of PEI 2.5 or 250 kDa and liposome containing derivative I had the highest transfection activity. Furthermore, non-viral vectors described in this study showed low cytotoxicity. The results show that small and large molecular weight linear PEI in combination with liposome have little toxicity and may enhance transfection efficiency.
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