[Resource for malaria research information on Internet].
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Biomedical subjects
Publications and source records attributed to H Zhai.
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Hydroquinone is a ubiquitous chemical readily available as monographed in cosmetic and nonprescription forms for skin lightening, and is an important industrial chemical. The in vivo bioavailability for 24-h application in humans was 45.3+/-11.2% of dose from a 2% cream formulation containing [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h. Timed skin wash and skin tape-stripping sequences showed a rapid and continuous movement of hydroquinone into the stratum corneum of human volunteers. Plasma levels taken both ipsilateral and contralateral to the topical dosing site contained radioactivity at the first 0.5-h sampling time. Peak plasma radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous absorption with fresh viable human skin gave a bioavailability of 43.3% of dose, and flux was calculated at 2.85 microg/cm2/h. In vitro, some of the skin samples were pretreated with the metabolic inhibitor sodium azide, which had no effect on percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were extracted and the extracts subjected to thin-layer chromatography (TLC). Control [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone. Receptor fluid and skin extraction had a second peak with the same Rf as benzoquinone, which was decreased with azide treatment. No other peaks were found. Ethyl acetate extraction of urine from the in vivo study showed all radioactivity to be only water-soluble, free hydroquinone released following glucuronidase treatment. Risk assessment should not only involve the bioavailability of intact topical hydroquinone, but also consider phase I and phase II metabolism in both humans and any animal for which toxicity potential was assessed.
The efficacy of a topical agent in barrier recovery was evaluated after acetone-induced acute water loss barrier disruption in vivo in humans. The upper back of several volunteers was rubbed with acetone-soaked cotton balls until elevated rates of transepidermal water loss (TEWL) occurred (> 20 g/m2h, or greater). The topical agent was then applied to the acetone-treated skin sites once daily for 5 days. Resolution evaluation used TEWL measurements and the data were expressed as the percentage recovery in water barrier function. In comparison with placebo control the topical agent significantly enhanced barrier recovery, especially within the first 72 h (P < 0.05). This model offers a simple method of examining chemicals accelerating (or inhibiting) repair of this form of acute skin damage in man.
BACKGROUND AND OBJECTIVE: The prediction of the irritation effects of products of low irritation potential remains problematic. An in vivo human model was utilized to define the irritation potential of a topical agent after partial removal of the stratum corneum by cellophane tape stripping. METHODS: The tape was applied to and removed approximately 50 times (mean, 50.0 +/- 16.7) from each test site on the volar aspect of the forearm. One site served as the stripping control, receiving tape stripping only. The other test sites received the topical agent and placebo control. Transepidermal water loss (TEWL) was measured before and daily for 5 days. The TEWL values at baseline after stripping represented the point of maximal stripping barrier disruption. The barrier disruption and irritation potential were assessed with TEWL measurements. RESULTS: The results showed that the model topical agent had no adverse effect on barrier repair, i.e. did not interfere with TEWL normalization. CONCLUSIONS: This model provides a method for the prediction, with exaggerated sensitivity, of chemical irritation and proclivity to enhance or retard water barrier repair. We believe that the model may predict the response of low irritation materials and may be more sensitive than patch testing on normal skin, particularly for products to be used on certain areas, e.g. the face, anus, etc., or even mucous membranes. The model must receive extensive use with chemicals of varying properties in order to define its chemical relevance.
A randomized, double-blind, placebo-controlled study was conducted to compare the efficacy of ammonium solution with placebo in relieving type I symptoms caused by Aedes aegypti mosquitoes on 25 healthy subjects. Each subject was bitten once under laboratory conditions by Aedes aegypti mosquitoes on the volar aspect of each forearm, and then received the treatment with ammonium solution and placebo, respectively. Compared with placebo, the ammonium solution significantly (p < 0.0001) decreased itching/burning/pain immediate type symptoms from 5 to 90 min. Complete and partial relief of the symptoms was noted in 64% in the ammonium solution group compared to none in the placebo group.
2 acute irritants and 1 allergen were selected: sodium lauryl sulfate (SLS) representative of irritant household and occupational contact dermatitis, the combination of ammonium hydroxide (NH4OH) and urea to simulate diaper dermatitis, and Rhus to evaluate the effect of model protective materials. The putative protective materials and vehicle were applied to both ventral forearms of 10 subjects in each group, according to a randomized code. Test materials were spread over a marked 2.0 cm2 area, massaged in, allowed to dry for 30 min, and reapplied with another 30 min drying period. The model irritants and allergen were then applied (0.025 ml) to an Al-test occlusive patch, which in turn was placed for 24 h over each of the 8 designated sites. Inflammation was scored according to a clinical scale 72 h post-application. Paraffin wax plus Acetulan in cetyl alcohol, and beeswax plus Acetulan in cetyl alcohol, markedly (p < 0.001) suppressed SLS irritation. Paraffin wax plus beeswax in cetyl alcohol, and Acetulan in cetyl alcohol reduced NH4OH and urea irritation (p < 0.05), paraffin wax in cetyl alcohol significantly (p < 0.01) decreasing Rhus allergic contact dermatitis. This model, provides an easy approach to screening protectants. Its clinical significance requires comparison with an open rather than an occluded challenge.
OBJECTIVE: To evaluate the therapeutic effect of the new method--adoptive cell immunotherapy on ovarian carcinoma. METHODS: Tumor soluble antigen (TSA) was extracted from cells of ovarian carcinoma (COC1 and COC2n). To generate cytotoxic T lymphocytes (CTL), peripheral blood mononuclear cells (PBMC) collected from healthy persons were induced by TSA and anti-CD3 monoclonal antibody (CD3-McAb). The antitumor effect of CTL on COC1 cells in vitro was compared with LAK and CD3-AK, whereas the growth inhibitory effect of CTL on COC2n transplantation tumors in nude mice was compared with CD3-AK. RESULTS: The cytotoxicity of CTL, CD3-AK and LAK was 79.4%, 52.1% and 51.7% respectively (P < 0.01). Mean volume of tumor in nude mice on the 9th day after ovarian carcinoma cells transplanted was 44.4 +/- 24.2 mm3 in CTL group, 118.8 +/- 40.0 mm3 in CD3-AK group and 443.0 +/- 158.7 mm3 in control (no treatment) (P < 0.01), whereas mean duration of survival was 28.5 days, 25.5 days and 17 days respectively (P < 0.01). CONCLUSION: The results indicated that CTL exhibited higher cytotoxic effect in vitro and greater inhibitory effect on tumor growth resulting in longer survival in vivo. It suggested that the adoptive cell immunotherapy might provide a new idea for treatment of ovarian carcinoma.
OBJECTIVE: To explore the effects of tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody (MAb) on tissue TNF-alpha and lipopolysaccharide-binding protein (LBP) mRNA expression, and multiple organ dysfunction in rats after thermal injury. METHOD: 24 male Wistar rats were subjected to a 35% total body surface area full-thickness thermal injury. RESULT: The tissue TNF-alpha and LBP mRNA expressions of liver, lung, intestine, and kidney were markedly increased (P < 0.05 approximately equal 0.01) after thermal injury. Treatment with TNF-alpha MAb could significantly lower TNF-alpha mRNA expression of lung, intestine and kidney, but had no effect on liver TNF-alpha mRNA expression (P > 0.05). Similarly, the tissue LBP mRNA expression also decreased significantly (36.0% - 72.9%), and returned to normal in lung, intestine and kidney. In addition, biochemical parameters including GPT, TBiL, BUN, CK-MB, and LDH were markedly elevated after thermal injury, and decreased significantly after treatment with TNF-alpha MAb. CONCLUSION: The increase of tissue TNF-alpha gene expression caused by thermal injury might be associated with a marked elevation of tissue LBP mRNA expression, which could contribute to the development of multiple organ dysfunction. The early use of TNF-alpha MAb seems to be effective in inhibiting significant LBP mRNA expression in various tissues and ameliorating multiple organ damage after major thermal injury.
Moisturizers, widely used in dermatologic and cosmetic "dry" skin treatments, can improve the skin condition by increasing stratum corneum water content and by other mechanisms. We review the controlled study data that relate to their use in the prevention of irritant contact dermatitis.
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An in vivo method was developed to measure the effectiveness of skin protective creams against 2 dye indicator solutions: methylene blue in water and oil red O in ethanol, representative of model hydrophilic and lipophilic compounds. 3 representative barrier creams commercialized as effective against lipophilic, hydrophilic, or lipophilic and hydrophilic substances were assayed by measurements of the dye in cyanoacrylate strips of protected skin samples after various application times. The flexural surfaces of the forearms of 6 normal volunteers (3 female and 3 male, mean age 26.8 +/- 4.1 years) were treated. The method was as follows: solutions of 5% methylene blue in water and 5% oil red O in ethanol were prepared, and applied to untreated skin and protective-cream-pretreated skin with the aid of aluminum occlusive chambers, for 0 h and 4 h, respectively. At the end of the application time, the creams were removed. Consecutive skin surface biopsies (SSB) from 1 to 4 strips were taken. The amount of stain in each strip was determined by colorimetry, and the cumulative amount of stain from 1 to 4 strips in each measurement was calculated. The cumulative amount represents the amount of permeation of each solution at each time point, and the efficacy of skin barrier cream. The results showed one formulation at both 0 h and 4 h reduced the amount of permeation of methylene blue (p < 0.01) and oil red O (p < 0.01) compared with the control group. Another formulation was protective against the permeation of oil red O (p < 0.01), but not against methylene blue at 0 h and 4 h; it was not significantly different at 0 h versus 4 h. The 3rd formulation produced increased cumulative amounts to oil red O at both 0 h and 4 h (p < 0.05); it also increased permeation amounts to methylene blue (p < 0.05) after 4 h. This model appears a facile, rapid and objective early screen to evaluate the efficacy of skin barrier creams in vivo, as well as their individual ingredients.
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Studies of the relationship of clinical and laboratory measures of accommodation and convergence function with refractive error are reviewed. There are inconsistencies in results from study to study presumably due, in part, to methodological differences. However, some basic trends can be outlined. In studies in young adults, accommodation in darkness (dark focus), optical reflex accommodation, and proximally induced accommodation are less in myopes than in emmetropes and hyperopes. It also appears that nearpoint esophoria is associated with higher rates of myopia progression in children. Implications for myopia etiology are discussed.
Using a phoro-accommodometer, accommodation and convergence responses were measured for 17 experimental subjects before and after they ingested 200 mg caffeine. For 16 control subjects accommodation and convergence responses were determined at two test sessions separated by 45 min. For the experimental group, the accommodative response/accommodative stimulus (Ar/As) slope increased 0.05 D/D after ingestion of caffeine, and the response AC/A ratio decreased 3.05 delta/D. The y-intercept of the convergence response/accommodative response increased by 3.7 delta in the experimental group. These changes were statistically significant. For the control group, the differences in Ar/As slope, response AC/A ratio, and convergence response/accommodative response y-intercept between first and second test sessions were not statistically significant.
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Few studies evaluate the effect of topical corticosteroids on thermal sensation and in alleviation of itch produced by intradermal injection of histamine. We evaluated the antipruritic effect of hydrocortisone (1% and 2.5%) on histamine-induced itch and sensory effects by measuring itch magnitude, itch duration and thermal thresholds using a computerized thermal sensory analyzer (TSA). This was a double-blind, random, comparative, controlled, single-dose and single-center study. Itch was experimentally induced in both forearms by intracutaneous injection of histamine in 18 subjects. Hydrocortisone 1%, 2.5% and placebo were applied to test sites on both forearms. The thermal threshold for warmth sensation, cold sensation, cold and heat pain was measured with the TSA. Itch magnitude was measured each minute after histamine injection for 10 min with a visual analogue scale (VAS). Itch duration was also recorded. In comparison to placebo, 2.5% hydrocortisone significantly (p = 0.03) reduced itch duration from 12.6 +/- 11.0 min (mean +/- SD) to 8.6 +/- 8.2 min (the reducing rate was 32%) as well as itch magnitude (at minutes 3, 6, 7 and overall). Placebo, 1% and 2.5% hydrocortisone significantly altered (p <0.05) the cold sensation threshold. No treatment altered cold or heat pain thresholds. These data suggest that topical application of 2.5% hydrocortisone may be significantly beneficial for the treatment of histamine-induced itch. The correlation between thermal measurements and antipruritic effects warrants further study.
Skin occlusion produces profound changes, including hydration status, barrier permeability, epidermal lipids, DNA synthesis, microbial flora, and numerous molecular and cellular processes. It often, but not always, increases percutaneous absorption of applied chemicals. This overview focuses on the effect of skin occlusion on percutaneous absorption.
Factors in the treatment of atopic dermatitis include restoring skin moisture and reducing inflammation. This study evaluated a corticoid oil formulation and its components with respect to their skin hydration potential. Ten healthy Caucasians were enrolled. Five test sites on the left and right forearm of each subject were tested: one site served as a normal skin control (without treatment), whereas four were wetted by spraying distilled water (approximately 0.1 ml) over a 3-cm2 skin surface area, and spraying was repeated every 5 min for a total of three applications. Five minutes after the final application, 0.2 ml of the corticoid oil formulation, moisturizing vehicle, and plain peanut oil were applied to each pre-designated site (3 cm2); one site was kept as a blank control (water saturation only). Thirty minutes later, test sites were gently wiped with paper tissues, and visual scoring, transepidermal water loss (TEWL), and capacitance were recorded and repeated at 2 and 3 h. The corticoid oil formulation, plain peanut oil, and moisturizing vehicle significantly increased skin hydration 30 min after each single application, with no statistically significant difference among the treatments at any point. The corticoid oil formulation and plain peanut oil slightly but not significantly elevated TEWL 30 min after application. The results support intuitive dermatologic judgment of advising patients to apply moisturizing medicaments after bathing.