In vivo percutaneous absorption of fragrance ingredients in rhesus monkeys and humans

The percutaneous absorption of the fragrance diethyl maleate was measured in vivo in human and monkey studies. With the application sites occluded, 54% of the applied dose of the volatile fragrance penetrated human skin in 24 hr compared with 69% absorption in the monkey skin. It was concluded that the monkey is a good model for human skin with regard to the penetration of this fragrance material since no significant difference in the absorption of diethyl maleate was observed. The percutaneous absorption of the fragrances benzyl acetate and five other benzyl derivatives (benzyl alcohol, benzyl benzoate, benzamide, benzoin and benzophenone) was determined in vivo in monkeys. Absorption through occluded skin was high for all compounds (approximately 70% of the applied dose in 24 hr) and no significant differences between the values for the different compounds were observed. No correlations were seen between skin penetration of these compounds and their octanol-water partition coefficients. Under unoccluded conditions skin penetration of the fragrances was reduced and there was great variability between compounds, presumably because of variations in the rates of evaporation from the site of application. The data suggest that humans may have significant systemic exposure to these fragrance materials.     

Can we get more from the Epworth Sleepiness Scale (ESS) than just a single score?

Purpose

The Epworth Sleepiness Scale (ESS) is a widely used tool for measuring sleepiness. In addition to providing a single measure of sleepiness (a one-factor structure), the ESS also has the capacity to provide additional information about specific factors that facilitate sleep onset, including a person’s posture, activity and environment. These features of sleepiness are referred to as somnificity. This study evaluates and compares the fit of a one-factor structure (sleepiness) and three-factor structure (reflecting low, medium and high levels of somnificity) for the ESS.

Methods

All participants (a community sample N?=?356 and a clinical sample N?=?679) were administered the ESS. Confirmatory factor analysis was used to evaluate and compare the fit of one- and three-factor models of the ESS.

Results

In both samples, a three-factor structure (community sample adjusted X ²?=?2.95, root mean square error of approximation (RMSEA)?=?0.07, Comparative Fit Index (CFI)?=?0.95; clinical sample adjusted X ²?=?3.98, RMSEA?=?0.07, CFI?=?0.98) provided a level of model fit that was at least as good as the one-factor structure (community sample adjusted X ²?=?5.01, RMSEA?=?0.11, CFI?=?0.87; clinical sample adjusted X ²?=?8.87, RMSEA?=?0.11, CFI?=?0.92).

Conclusions

In addition to a single measure of sleepiness, the ESS can provide subscale scores which relate to three underlying levels of somnificity. These findings suggest that the ESS can be used to measure an individual’s overall sleep propensity as well as more specific measures of sleep propensity in low, moderate and high levels of situational somnificity.     

Predicting uptake of continuous positive airway pressure (CPAP) therapy in obstructive sleep apnoea (OSA): a belief-based theoretical approach

Purpose

Obstructive sleep apnoea (OSA) is a common disorder, for which continuous positive airway pressure (CPAP) therapy is a standard treatment. Despite its well-established efficacy, many patients choose not to initiate CPAP treatment. The present study investigated the degree to which biological measures (e.g. Apnoea–Hypopnoea Index [AHI]), symptom experiences (e.g. fatigue) and illness representations (e.g. perceived consequences) predict the decision of individuals newly diagnosed with OSA to undergo a trial of CPAP therapy.

Methods

Four hundred forty-nine individuals (316 males) newly diagnosed with OSA. Epworth sleepiness scale (ESS), Fatigue Severity Scale, Depression Anxiety Stress Scale and Illness Perception Questionnaire-Revised (IPQ-R) were administered at time of sleep study. These, patient demographics and sleep study variables were used to determine factors predicting patient decision to proceed with a trial of CPAP.

Results

The participants were most likely to attribute their OSA to unchangeable and psychological factors. For those with moderate OSA (AHI, 15 to 30) IPQ-R illness consequence was predictive of decision to initiate CPAP (p = 0.002). For severe OSA (AHI >30) age, ESS and IPQ illness causal beliefs were predictive of decision to initiate CPAP (p < 0.001).

Conclusions

Illness beliefs are important determinants of the choice of recently diagnosed OSA patients whether or not to undertake a trial of CPAP therapy. Concerns about illness consequences were important in those with moderate OSA. In severe OSA, sleepiness symptoms are more prominent and a more significant determinant of CPAP uptake along with age and causal beliefs.     

Multisensory stimulation to improve functional performance in moderate to severe dementia--interim results

Dementia is a growing problem worldwide and interventions to effectively manage and promote function are urgently required. Multisensory environments (MSEs) have been used extensively with people with dementia; however, no studies have been conducted to explore the efficacy of sensory stimulation on functional performance. This study explores to what extent multisensory stimulation influences functional performance in people with moderate-to-severe dementia using an MSE compared with a control activity. Thirty participants with moderate-to-severe dementia were recruited from the South of England. Following baseline assessment and design of a bespoke intervention, each participant attended their allocated intervention (3 x week, for 4 weeks). Assessments were carried out pre and postsession using the Assessment of Motor and Process Skills. Results indicate significant improvement in functional performance in both the MSE and the control activity. Findings support the use of MSEs as a strategy for enhancing functional performance in dementia.     

In vitro percutaneous absorption and stratum corneum binding of alachlor: Effect of formulation dilution with water

The effect of vehicle dilution on the percutaneous absorption of alachlor, 2-chloro-2′,6′-diethyl-N-(methoxymethyl)acetanilide, through excised human skin was determined using flowthrough design glass penetration cells and ¹⁴C radiotracer methodology. Three dilutions of alachlor (in the solubilizing commercial formulation) with distilled water were utilized: 1:20, 1:40, and 1:80 (v/v); corresponding to concentrations of 23.0, 11.8, and 5.98 mg alachlor per milliliter, respectively. Skin from the penetration studies and human powdered stratum corneum from the binding studies demonstrated a high capacity for alachlor. A soap and water (1:1, v/v) solution effectively decontaminated powdered stratum corneum. Using plasma as the receptor solution, penetration ranged from 0.5 to 4% of the applied dose for an 8-hr exposure period. Lag times of 1.2 to 1.8 hr were observed. Increasing dilution resulted in significant enhancement (p < 0.01) in the rate and extent of alachlor penetration. Although the biological significance of this observation is unclear, this phenomenon might be explored in future studies because of its ramifications for human toxicity and for decontamination opportunities.     

Percutaneous absorption and skin decontamination of PCBs: in vitro studies with human skin and in vivo studies in the rhesus monkey

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing.     

Percutaneous absorption of malathion in the guinea-pig: effect of repeated topical application

The effects of daily repeated topical application and of washing on the percutaneous absorption of malathion have been investigated in guinea-pigs. Skin absorption was determined indirectly by measurement of radioactivity excreted into the urine following topical administration of 14C-labelled malathion, with correction of these values for incomplete renal elimination. Malathion was applied at a concentration of 5 mg/cm2 every 24 hr to the same site on the post-auricular bald area for 15 days. Doses 1, 8 and 15 were radiolabelled. The effect of multiple application and washing was assessed by Newman-Keuls multiple range test for statistical significance. The percutaneous absorption of malathion was 2-3 times higher with washing than without. There was no significant increase (P greater than 0.05) in the percutaneous absorption of malathion with repeated application without washing. These studies suggest that the total penetration of malathion resulting from daily topical dosing without daily washing may be predicted from a single-dose application to the same unwashed site at an equivalent surface concentration, and also that repeated washing with soap and water may significantly decrease the barrier function of guinea-pig skin.     

Bioavailability of topically administered steroids: a "mass balance" technique

The percutaneous absorption of four steroids (hydrocortisone, estradiol, testosterone, and progesterone) has been measured in vivo in man under occluded and "protected" (i.e., covered, but non-occlusive) conditions. The experimental approach, involving simple modifications of standard radiochemical methodology, has enabled excellent "mass balance" and dose accountability to be achieved. Consequently, the utility of the procedure for the measurement of in vivo topical bioavailability can be inferred. In addition, because of the precision and accountability of the results, the technique offers a potential means to establish quantitative structure-penetration relationships for skin absorption in man. It was found that steroid absorption increased with increasing lipophilicity up to a point, but that penetration of progesterone (the most hydophobic analog studied) did not continue the trend and was at least partly rate-limited by slow interfacial transport at the stratum corneum-viable epidermis boundary. Comparison of data obtained from the occluded and "protected" experiments permitted the effect of occlusion (defined as the complete impairment of passive transepidermal water loss at the application site) to be assessed. Occlusion significantly increased percutaneous absorption of estradiol, testosterone, and progesterone but did not effect the penetration of hydrocortisone. A mechanism is proposed to explain why the absorption of the more lipophilic steroids is enhanced by occlusion but that of the most water-soluble (i.e., hydrocortisone) is not. It is suggested that the rate-determining role of the sequential steps involved in percutaneous absorption can be revealed by experiments of the type described using related series of homologous or analogous chemicals.