To study the relationship between the intensity of the stimulus exerted against the base of the tongue during direct laryngoscopy and the magnitude of associated hemodynamic and catecholamine responses, a study was conducted in 40 ASA I or II patients. Laryngoscopy lasting 40 s was performed with a size 3 Macintosh blade connected to a force-displacement transducer. The intensity of the stimulus exerted during laryngoscopy is expressed by the product of its average force (N) and duration (s) and given as impulse in Ns. Highly significant relationships were found between the impulse during laryngoscopy and the maximal hemodynamic and catecholamine responses. Also, when laryngoscopy was followed by orotracheal intubation, significant relationships were found with steeper slopes of the regression lines for systolic blood pressure, heart rate and plasma epinephrine concentrations. A more rapid regression of hemodynamic data was seen in intubated patients, whereas their plasma catecholamine concentrations regressed more slowly. The mechanisms of the responses to laryngoscopy and orotracheal intubation are proposed to be by somato-visceral reflexes. Stimulation of proprioceptors at the base of the tongue during laryngoscopy induces impulse-dependent increases of systemic blood pressure, heart rate and plasma catecholamine concentrations. Subsequent orotracheal intubation recruits additional receptors that elicit augmented hemodynamic and epinephrine responses as well as some vagal inhibition of the heart.

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BackgroundSynthetic antioxidants and antimicrobials are losing ground to their natural counterparts and therefore, the food industry has motivated to seek other natural alternatives. Apple pomace, a by-product in the processing of apples, is rich in polyphenols, and plant polyphenols have been used as food additives owing to their strong antioxidant and antimicrobial properties. The goal of this study was to screen the individual polyphenols with antioxidant and antimicrobial activities from the extracts (methanol, ethanol, acetone, ethyl acetate, and chloroform) of Golden Delicious pomace.ResultsFirst, the polyphenolic compounds (total phenol content, TPC; total flavonoids, TFD; total flavanols, TFL) and antioxidant activities (AAs) with four assays (ferric reducing antioxidant power, FRAP; 1,1-diphenyl-2-picryhydrazyl radical scavenging capacity assay, DRSC; hydroxyl radical averting capacity assay, HORAC; oxygen radical absorbance capacity assay, ORAC) were analyzed. The results showed a significant positive correlation (P < 0.05) between AAs and TFD. Ethyl acetate extract (EAE) exhibited the highest TFD with a concentration of 1.85 mg RE/g powder (expressed as rutin equivalents), and the highest AAs (expressed as butylated hydroxytoluene (BHT) equivalents) with 2.07 mg BHT/g powder for FRAP, 3.05 mg BHT/g powder for DRSC, 5.42 mg BHT/g powder for HORAC, and 8.89 mg BHT/g powder for ORAC. Composition and AA assays of individual polyphenols from the EAE were then performed. Phloridzin and phloretin accounted for 46.70 and 41.94 % of TFD, respectively. Phloretin displayed the highest AA, followed by phloridzin. Finally, the antimicrobial activities of the EAE, phloridzin, and phloretin were evaluated. EAE displayed good inhibitory activities against Staphylococcus aureus with a minimum inhibition concentration (MIC) of 1.25 mg/ml and against Escherichia coli with a MIC of 2.50 mg/ml. Phloridzin and phloretin showed better inhibitory activities than the EAE, which were MICs of 0.50 and 0.10 mg/ml, respectively, against S. aureus and MICs of 1.50 and 0.75 mg/ml, respectively, against E. coli.ConclusionsEthyl acetate was the best solvent of choice to extract natural products to obtain the maximum antioxidant and antibacterial benefits. Phloridzin and phloretin have the potential to be used as natural alternatives to synthetic antioxidants and antimicrobials.

Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.

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