Topical applications of an emollient reduce circulating pro-inflammatory cytokine levels in chronically aged humans: a pilot clinical study.

BACKGROUND: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE: We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS: Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1ß, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS: We also found significantly higher baseline levels of IL-1ß, IL-6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL-1ß and IL-6 normalized, while TNFα levels declined substantially. CONCLUSION: The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro-inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.

Epidermal permeability barrier recovery is delayed in vitiligo-involved sites.

BACKGROUND/OBJECTIVES: Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. METHODS: A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13-51 years (mean age: 27.91 +/- 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. RESULTS: In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 +/- 5.39% vs. 58.30 +/- 4.71%; t = 2.441; p < 0.02). CONCLUSION: Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo.

Decreased cutaneous resonance running time in cured leprosy subjects.

BACKGROUND/OBJECTIVES: Leprosy prominently involves both the skin and peripheral neural tissues and some symptoms persist after microbial cure. Because alterations in the dermis also occur in leprosy, we assessed here whether there were changes in cutaneous resonance running time (CRRT), a parameter that is influenced by collagen properties, in cured leprosy subjects. METHODS: A reviscometer was used to measure the CRRT at various directions on the dorsal hand and the flexural forearms of 76 cured leprosy subjects aged 50-85 years and 68 age-matched normal subjects. RESULTS: In comparison to normal subjects, CRRTs on the hands and the forearms were significantly reduced in all directions in cured leprosy, except at the 1-7, 2-8 and 3-9 o'clock directions on the forearms. CRRTs were reduced significantly at both the 4-10 and 5-11 o'clock directions on the forearm in lepromatous (73.33 +/- 4.19 at 4-10 o'clock and 67.44 +/- 2.71 at 5-11 o'clock direction) and borderline lepromatous types (77.58 +/- 5.84 at 4-10 o'clock and 79.85 +/- 6.81 at 5-11 o'clock direction) as compared with normal (143.10 +/- 7.75 at 4-10 o'clock and 125.18 +/- 8.14 at 5-11 o'clock direction). On the hand, CRRTs at all directions, except that at 4-10 o'clock direction, were also significantly reduced in lepromatous and borderline lepromatous types in comparison with normal. Significant differences in CRRT at some directions were found among the various subtypes of leprosy. CONCLUSION: CRRTs were abnormal in the cured leprosy subjects as a whole, but varied with leprosy subtypes, which suggested that the extent of reduction of CRRTs correlates with the severity of immune alteration. These results suggest that CRRT measurements could be a useful approach to quantify the extent of some residual abnormalities in cured leprosy and perhaps could also be used to evaluate the efficacy of treatment.

Abnormalities in stratum corneum function in patients recovered from leprosy.

BACKGROUND AND OBJECTIVES: Leprosy involves both the skin and peripheral nervous system. Leprosy patients display an increased incidence of xerosis and altered sensory thresholds, which persist in previously active skin sites. We assessed here whether alterations in stratum corneum (SC) function persist in cured leprosy, and the relationship of epidermal functional abnormalities to each clinical subtype of leprosy. METHODS: A total of 43 cured leprosy subjects and 29 normal control subjects were enrolled in this study. Basal skin surface pH, SC hydration, permeability barrier function as well as barrier recovery rates were measured over previously involved skin sites with a skin physiology monitor. One-way ANOVA and two-tailed Student's t test were used to determine the significance between 2 groups and 3 or more groups, respectively. RESULTS: Competent barrier function was observed in all subtypes of cured leprosy subjects. All cured leprosy subjects except those with the borderline tuberculoid type exhibited a significantly lower SC hydration in comparison with normal subjects. Skin surface pH was significantly elevated in all cured leprosy subjects in comparison with normal subjects. CONCLUSIONS: A varied spectrum of alterations in SC function remains in all subjects who have recovered from leprosy, but the spectrum of SC functional abnormalities varies with disease subtype.

Xenon-CT study of regional cerebral blood flow around hematoma in patients with basal ganglia hemorrhage.

BACKGROUND: Xenon-CT is a quantitive technique for estimating cerebral blood flow. To investigate whether penumbra exists around hematoma, regional cerebral blood flow (ICBF) was measured by Xenon-CT in patients with intracerebral hemorrhage (ICH). METHODS: Xenon-CT was performed on 15 patients with basal ganglia hemorrhage and hematoma volume < 50 mL. rCBF was measured within 36 h of onset and an average of 13 days later by 27-pixel rings in perihematomal area and its enantiomorph in contralateral hemisphere. Penumbra was defined as rCBF 8-20 mL x 100 g(-1) x min(-1). RESULTS: Average ICH volume was 13 +/- 7 mL (6.4-23.7 mL). First rCBF examination was conducted at 21.7 +/- 9.4 h (5-37 h), second rCBF examination was conducted at 13.4 +/- 1.8 days (11-18 days) after onset. Within 36h of onset, mean perihematomal rCBF was 28.4 +/- 7.8 mL x 100 g(-1) x min(-1); contralateral region was 34.2 +/- 12.2 mL x 100 g(-l) x min(-1) (p = 0.11). Average 13 days after onset, mean rCBF close to hematoma was 19.4 +/- 8.1 mL x 100 g(-1) x min(-1); rCBF in contralateral region was 40.1 +/- 11.3 mL x 100 g(-1) x min(-1) (p < 0.0001). rCBF in distal perihematomal region was 27.8 +/- 9.5 mL x 100 g(-1) x min(-1); the difference was significant compared to contralateral region (p = 0.0003). One patient's rCBF in area of edema around hematoma was less than 20 mL x 100 g(-1) x min(-1) at first examination. At second examination, 6 patients had same occurrence in region adjacent to hematoma and 2 patients experienced it in distal perihematomal region. CONCLUSIONS: Reduced perihematomal rCBF was shown after ICH; this phenomenon lasted at least 14 days. A number of ICH patients experienced penumbra around hematoma.