Olfactory and trigeminal interaction of menthol and nicotine in humans

The purpose of the study was to investigate the interactions between two stimuli—menthol and nicotine—both of which activate the olfactory and the trigeminal system. More specifically, we wanted to know whether menthol at different concentrations modulates the perception of burning and stinging pain induced by nicotine stimuli in the human nose. The study followed an eightfold randomized, double-blind, cross-over design including 20 participants. Thirty phasic nicotine stimuli at one of the two concentrations (99 and 134 ng/mL) were applied during the entire experiment every 1.5 min for 1 s; tonic menthol stimulation at one of the three concentrations (0.8, 1.5 and 3.4 μg/mL) or no-menthol (placebo control conditions) was introduced after the 15th nicotine stimulus. The perceived intensities of nicotine’s burning and stinging pain sensations, as well as perceived intensities of menthol’s odor, cooling and pain sensations, were estimated using visual analog scales. Recorded estimates of stinging and burning sensations induced by nicotine initially decreased (first half of the experiment) probably due to adaptation/habituation. Tonic menthol stimulation did not change steady-state nicotine pain intensity estimates, neither for burning nor for stinging pain. Menthol-induced odor and cooling sensations were concentration dependent when combined with low-intensity nicotine stimuli. Surprisingly, this dose dependency was eliminated when combining menthol stimuli with high-intensity nicotine stimuli. There was no such nicotine effect on menthol’s pain sensation. In summary, we detected interactions caused by nicotine on menthol perception for odor and cooling but no effect was elicited by menthol on nicotine pain sensation

Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery—a pilot study

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E2 (PGE2) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs(O–24h)] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2–7%). Individual CSF lag times with respect to (50%) peak plasma concentration were ≤2 h in all but one case (median: 1 h). PGE2 production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE2 production at the presumed site of action

Herb&ndash;Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplements

Many people worldwide use plant preparations for medicinal purposes. Even in industrialized regions, such as Europe, where conventional therapies are accessible for the majority of patients, there is a growing interest in and usage of phytomedicine. Plant preparations are not only used as alternative treatment, but also combined with conventional drugs. These combinations deserve careful contemplation, as the complex mixtures of bioactive substances in plants show a potential for interactions. Induction of CYP enzymes and pGP by St John&rsquo;s wort may be the most famous example, but there is much more to consider. In this review, we shed light on what is known about the interactions between botanicals and drugs, in order to make practitioners aware of potential drug-related problems. The main focus of the article is the treatment of inflammatory diseases, accompanied by plant preparations used in Europe. Several of the drugs we discuss here, as basal medication in chronic inflammatory diseases (e.g., methotrexate, janus kinase inhibitors), are also used as oral tumor therapeutics

Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat)

OBJECTIVES: The aim of this review is to examine the causes, pathophysiology and experimental models of non-infectious pharyngitis (sore throat). INTRODUCTION: The causes of sore throat can be infectious (viruses, bacteria, and fungi) or non-infectious, although the relative proportion of each is not well documented. METHODS: A PubMed database search was performed for studies of non-infectious sore throat. RESULTS AND CONCLUSIONS: Non-infectious causes of sore throat include: physico-chemical factors, such as smoking, snoring, shouting, tracheal intubation, medications, or concomitant illness; and environmental factors including indoor and outdoor air pollutants, temperature and humidity, and hazardous or occupational irritants. The pathophysiology underlying non-infectious sore throat is largely uncharacterised, although neurogenic inflammation looks to be a promising candidate. It is likely that there will be individual disposition factors or the coincidence of more than one irritant with possible—up to now unknown—interactions between them. Therefore, experimental models with defined conditions and objective endpoints are needed. A new model using cold dry air to directly induce pharyngeal irritation in humans, with pharyngeal lavage to measure biomarkers, may provide a useful tool for the study of mechanisms and treatment of non-infectious sore throat

A Novel Device for the Clinical Assessment of Intranasal Trigeminal Sensitivity

Objective: Despite the significance of trigeminal pathology, practical clinical tests that accurately evaluate intranasal trigeminal function are scarce. The aim of the present study is to introduce a practical procedure for the assessment of intranasal trigeminal sensitivity. Methods: We developed a device to stimulate the nasal mucosa using carbon dioxide, which is self-administered intranasally by holding down a timed button until the required sensory response has been triggered. The trigeminal sensitivity is derived from the measured administration time in conjunction with the concentration of carbon dioxide administered. Sixty-three healthy participants were used to validate the device, after which the new device was compared with a standard lateralization task in an additional 16 participants. In 20 participants, the experiment was repeated to verify test–retest reliability. Results: Statistical analysis showed significant consistency in administration-duration in healthy individuals, including those in the test–retest group. Those participants with higher scores in the lateralization task were found to show higher intranasal sensitivity measured by the new device. Conclusion: Herein, we present the design and validation of a novel device for the practical assessment of intranasal trigeminal sensitivity. In this study, we demonstrate the efficacy and reliability of this device

Gustatory Function in Patients With Chronic Rhinosinusitis

Objectives: Recent research has shown that taste receptors in airway epithelial cells are involved in defending against upper respiratory tract infection. The aim of the present study was to investigate gustatory function in patients with chronic rhinosinusitis (CRS). Methods: Taste function was assessed using the extended “taste strip” test in 37 patients with CRS (20 males, 17 females; mean age = 32.1 years; range, 20-82 years) and 135 healthy controls (70 males, 65 females; mean age = 29.5 years; range, 18-84 years). Results: The mean (±SD) total extended taste score was 12.8 (±3.5) in patients and 14.5 (±3.2) in controls. Analysis of variance indicated an interaction of sinusitis and gender (P < .05) with significantly lower total scores and significantly poorer results for the bitter taste among male patients compared to controls (P < .01). In addition, CRS patients exhibited a trend toward decreased sweet taste perception compared to controls, but this did not reach significance (P = .051). Conclusions: Patients with CRS exhibited decreased gustatory function compared to healthy controls. The effect was most pronounced for bitter taste. Thus, the assessment of gustatory function seems to be useful for detecting potential risk factors for recurrent upper respiratory tract infection

Ibuprofen plasma concentration profile in deliberate ibuprofen overdose with circulatory depression treated with therapeutic plasma exchange: a case report

Background Inquiries relating to ibuprofen overdose have more than tripled in the last ten years in our poison control center. Although the vast majority of cases have a benign clinical course, there are few severe or even fatal cases present with refractory circulatory failure. Case presentation We describe a case of a 48 year-old male with suicidal mono-ingestion of approximately 72 g ibuprofen. Despite an initial rapid spontaneous drop in the total ibuprofen plasma concentration (IPC) from 550 to 275 mcg/mL within the first 5 h after admission, the patient developed a circulatory failure, refractory to aggressive fluid resuscitation and high doses of vasopressors. Due to ibuprofen’s favorable pharmacokinetics (>95% bound to albumin, low volume of distribution) and in the absence of specific therapeutic alternatives thereby avoiding escalating vasopressor doses, therapeutic plasma exchange (TPE) for extracorporeal elimination of ibuprofen was considered as a therapeutic rescue option. An improvement of hemodynamics with a significant reduction of vasopressors was observed with TPE-initiation. However, neither the observed IPC-profile nor a pharmacokinetic (PK) simulation provided evidence for a quantitative effective elimination of ibuprofen by TPE. Based on PK-modeling we calculated an overall ibuprofen half-life of 17.2 h for the entire observation period over 5 days. Conclusions To our knowledge this is the first report of a severe ibuprofen-mono intoxication treated with TPE and providing serial IPCs over a period of five days, indicating an estimated fivefold overall-elimination half-life of 17.2 h. Despite TPE clinically improved persistent hemodynamic instability, this procedure was neither consistent with the observed IPC-profile nor correlated with a meaningful quantitative elimination of ibuprofen

Consumption of analgesics before a marathon and the incidence of cardiovascular, gastrointestinal and renal problems: a cohort study

Objectives: To prevent pain inhibiting their performance, many athletes ingest over-the-counter (OTC) analgesics before competing. We aimed at defining the use of analgesics and the relation between OTC analgesic use/dose and adverse events (AEs) during and after the race, a relation that has not been investigated to date. Design: Prospective (non-interventional) cohort study, using an online questionnaire. Setting: The Bonn marathon 2010. Participants: 3913 of 7048 participants in the Bonn marathon 2010 returned their questionnaires. Primary and secondary outcomes: Intensity of analgesic consumption before sports; incidence of AEs in the cohort of analgesic users as compared to non-users. Results: There was no significant difference between the premature race withdrawal rate in the analgesics cohort and the cohort who did not take analgesics (‘controls’). However, race withdrawal because of gastrointestinal AEs was significantly more frequent in the analgesics cohort than in the control. Conversely, withdrawal because of muscle cramps was rare, but it was significantly more frequent in controls. The analgesics cohort had an almost 5 times higher incidence of AEs (overall risk difference of 13%). This incidence increased significantly with increasing analgesic dose. Nine respondents reported temporary hospital admittance: three for temporary kidney failure (post-ibuprofen ingestion), four with bleeds (post-aspirin ingestion) and two cardiac infarctions (post-aspirin ingestion). None of the control reported hospital admittance. Conclusions: The use of analgesics before participating in endurance sports may cause many potentially serious, unwanted AEs that increase with increasing analgesic dose. Analgesic use before endurance sports appears to pose an unrecognised medical problem as yet. If verifiable in other endurance sports, it requires the attention of physicians and regulatory authorities

Chemo-somatosensory evoked potentials : A sensitive tool to assess conditioned pain modulation?

UNLABELLED: Abstract Background: Chemo-somatosensory evoked potentials (CSSEPs) elicited by chemical stimulation (CO₂ gas) of the nasal mucosa have been shown to be sensitive enough to pick up even weak analgesic effects. With the present study we wanted to investigate whether CSSEPs are also a sensitive tool to capture endogenous pain inhibitory mechanisms elicited by conditioned pain modulation (CPM; where a first conditioning stimulus reduces the sensitivity for a second test stimulus) with a conditioning stimulus of rather low noxious load. METHODS: Seventeen healthy participants were tested for CPM effects (conditioning stimulus: tonic heat pain with intensities around the pain threshold induced via a thermode; test stimulus: chemonasal stimulation (73% and 78% CO₂)) on CSSEPs and on self-report ratings. RESULTS: We found significant CPM effects in the CSSEPS, with reduced amplitudes and prolonged latencies at several electroencephalogram (EEG) recording positions when using the lower CO₂ concentration (73% CO₂). In contrast to the visible inhibitory effects on the CSSEPs, subjective ratings of the test stimulus did not reflect CPM action. DISCUSSION: The experimental pain model using CO₂ stimuli to elicit CSSEPs proved to be sensitive enough to capture weak CPM effects elicited by a conditioning stimulus of rather low noxious load. The usage of such mild noxious conditioning stimuli-in contrast to stimuli of higher noxious load (e.g., cold pressor test)-has the advantage that the activation of other types of pain inhibitory mechanisms in parallel (like attentional distraction, stress-induced analgesia) can be avoided

The Laryngoscope / Olfactory implant : Demand for a future treatment option in patients with olfactory dysfunction

Objectives Therapeutic options in olfactory dysfunction (OD) are limited. Numerous studies have shown impact of OD on quality of life. Lately, various studies support benefits of olfactory training, but therapyrefractory cases leave doctors and patients locked in a stalemate. An olfactory implant (OI), in analogy to the widely successful cochlear implant, still seems far away from realization. The present study sought to evaluate the demand of OI in patients with OD. Methods Sixtyone patients (28 females and 33 males, mean age/standard deviation 54.9/17.6 years) with OD were recruited. We performed olfactory testing for threshold (T), discrimination (D), and identification (I) using Sniffin' Sticks; summed scores (TDI) allowed us to determine normosmia, hyposmia, and anosmia. We applied questionnaires on the importance of smell (IOS), on olfactory disorders (QOD) and on the interest/willingness for OI, considering the need for skull base/head surgery. Results Twentyone patients (34.4%) stated that OI could be a future treatment option for them. This decision significantly correlated with TDI, I, complaintrelated questions of the QOD, and IOS (P<.05). Conclusion With approximately onethird of patients considering OI as a therapy option, this study seems to indicate a demand for OI. In selected patients, with a high degree of complaints, low olfactory test scores, and maybe an additional occupational need for olfactory function, OI might be an option if future developments warrant safety of OI procedures.(VLID)341177