Mitochondria and redox homoeostasis as chemotherapeutic targets of Araucaria angustifolia (Bert.) O. Kuntze in human larynx HEp-2 cancer cells.

Natural products are among one of the most promising fields in finding new molecular targets in cancer therapy. Laryngeal carcinoma is one of the most common cancers affecting the head and neck regions, and is associated with high morbidity rate if left untreated. The aim of this study was to examine the antiproliferative effect of Araucaria angustifolia on laryngeal carcinoma HEp-2 cells. The results showed that A. angustifolia extract (AAE) induced a significant cytotoxicity in HEp-2 cells compared to the non-tumor human epithelial (HEK-293) cells, indicating a selective activity of AAE for the cancer cells. A. angustifolia extract was able to increase oxidative damage to lipids and proteins, and the production of nitric oxide, along with the depletion of enzymatic antioxidant defenses (superoxide dismutase and catalase) in the tumor cell line. Moreover, AAE was able to induce DNA damage, nuclear fragmentation and chromatin condensation. A significant increase in the Apoptosis Inducing Factor (AIF), Bax, poly-(ADP-ribose) polymerase (PARP) and caspase-3 cleavage expression were also found. These effects could be related to the ability of AAE to increase the production of reactive oxygen species through inhibition of the mitochondrial electron transport chain complex I activity and ATP production by the tumor cells. The phytochemical analysis of A. angustifolia, performed using High Resolution Mass Spectrometry (HRMS) in MS and MS/MS mode, showed the presence of dodecanoic and hexadecanoic acids, and phenolic compounds, which may be associated with the chemotherapeutic effect observed in this study.

Study to assess the laryngeal and pharyngeal spread of topical local anesthetic administered orally during general anesthesia in children.

BACKGROUND: Topical local anesthesia of the airway of anaesthetized children has many potential benefits. In our institution, lignocaine is topically instilled blindly into the back of the mouth with the expectation that it will come into contact with the larynx. The volume and method of application varies between clinicians. There is no published evidence to support the plausibility of this technique. AIM: To determine whether this technique of instillation results in the local anesthetic coming into contact with key laryngeal structures and whether this is influenced by volume or additional physical maneuvers. METHODS/MATERIALS: Sixty-three healthy anaesthetized children between 6 months and 16 years old had lignocaine stained with methylene blue poured into the back of their mouths. The volume and subsequent physical maneuver were determined by randomization. A blinded observer assessed staining of the vocal cords, epiglottis, vallecula and piriform fossae by direct laryngoscopy. Airway complications were recorded. RESULTS: Fifty-three of the 63 children had complete staining of all four areas. Four children had one area unstained, and all others had at least partial staining of all four structures. Nine children coughed following induction of anesthesia. Coughing was more likely in children with incomplete staining (P = 0.03), low volume lignocaine (P = 0.003) and following a head lift (P = 0.02). CONCLUSION: Oral administration of lignocaine without use of a laryngoscope frequently results in widespread coverage of key laryngeal structures and may reduce the risk of coughing.

Secretory response induced by essential oils on airway surface fluid: a pharmacological MRI study.

Using pharmacological magnetic resonance imaging, we have performed an in vivo evaluation of the secretory response induced by essential oils in the rat airway. Aim of the work was to establish a computerized method to assess the efficacy of volatile compounds in spatially localized areas without the bias derived by subjective evaluation. Magnetic resonance experiments were carried out using a 4.7 T horizontal magnet. In the trachea, airway surface fluid was easily identified for its high intensity signal. The tracheal glands were also easily visible. The oesophageal lumen was usually collapsed and was identifiable only in the presence of intraluminal liquid. Scotch pine essential oil inhalation significantly increased the surface fluid in the middle portion of the trachea and the increase was visible at both 5 and 10 min. A lesser secretory response was detected after rosemary essential oil inhalation even though the response was significant with respect to the control in particular at 10 min. No secretory response was detected after peppermint essential oil inhalation both at 5 and 10 min. The data obtained in the present work demonstrate a chemically induced airway secretion. The availability of a pharmacological magnetic resonance imaging approach opens new perspectives to test the action of volatile compounds on the airway.

Double-blind study on the effects of topical anesthesia on laryngeal secretions.

The application of topical anesthesia to the oropharynx is a common clinical practice during oral and nasal laryngoscopy. Clinically, questions have been raised about whether topical anesthesia alters laryngeal secretions, which distorts clinical impressions. A double-blind, placebo controlled design was employed to address this issue. Ten premenopausal women with healthy vocal folds and 10 premenopausal women with phonotraumatic lesions underwent oral videolaryngoscopic examinations on subsequent days under both anesthesia and placebo conditions, in counterbalanced order. Video segments were rated by three judges. Dependent variables were balling and pooling of secretions, as previously described in the literature. Statistical analyses failed to reveal any clear effect of topical anesthesia on either secretion balling or pooling for the collapsed data set, but one cannot exclude changes in individual cases. Moreover, there was no evidence that secretions were differentially affected by anesthesia across subject groups. Null results in this data set replicate and extend previously reported findings by other authors. An incidental but potentially interesting finding was that the order of treatment condition (anesthesia versus placebo first) seemed relevant for secretions: Subjects who received the anesthesia condition first tended to show more secretion balling in general, as compared with subjects who received the placebo condition first. Speculation is entertained regarding possible physiological pathways for these incidental findings, which could be relevant for some clinical practice.

Topical anaesthesia of the larynx: cocaine or lignocaine?

A double-blind, randomized study compared the cardiovascular responses and extubation conditions using lignocaine or cocaine for topical anaesthesia of the larynx. Absorption of both agents from the trachea was quantified by serial venous plasma concentrations. Serial blood pressure, ECG, O2 saturation and end-tidal carbon dioxide measurements were obtained. Conditions at extubation were assessed on duration of coughing, graded on a scale of 1-4 (1 = no coughing, 2 = single cough, 3 = coughing lasting less than 30 s, 4 = coughing lasting 30 s or more). No difference was found in cardiovascular measurements between the two groups. The patterns of absorption of cocaine and lignocaine from the laryngeal mucosa were very similar, with peak absorption occurring at 10-15 min after laryngeal spraying. Although cocaine reduced the incidence of post-operative coughing when compared with lignocaine, this did not reach statistical significance.