Impaired niacin sensitivity in acute first-episode but not in multi-episode schizophrenia

Niacin (vitamin B3) flushing--a marker of altered prostaglandin signaling--is indirectly linked to the phospholipid-prostaglandin metabolism. Diminished skin flushing was repeatedly found in schizophrenia, but has not been systematically investigated at different stages of disorder as yet. We compared niacin sensitivity of 32 first-episode and 32 multi-episode patients (mainly on stable medication) with age and gender matched healthy controls. Methylnicotinate was applied in three concentrations onto the inner forearm skin. Flush response was assessed in 3 min intervals over 15 min using optical reflection spectroscopy. Whereas first-episode patients showed significantly diminished flush response as compared to controls, comparable differences were not found between multi-episode patients and controls. Comparison of niacin sensitivity at different stages of schizophrenia support the notion of altered prostaglandin signaling primarily at the onset of disorder. Longitudinal studies have to rule out possible long-term effects of neuroleptic medication.     

Endophenotype properties of niacin sensitivity as marker of impaired prostaglandin signalling in schizophrenia

BACKGROUND: Disruption of arachidonic acid pathways and prostaglandin signalling has been implicated in the pathophysiology of schizophrenia. AIMS: We intended to study prostaglandin signalling in groups of young schizophrenia patients, first-degree relatives, and healthy controls in order to assess effects of heritability on this biological marker-one important endophenotype criterion. METHOD: Namely, we assessed intensity of methylnicotinate skin flushing using optical reflection spectroscopy. Tests were applied to 19 adolescent first-episode schizophrenia patients, 21 first-degree relatives, and groups of age and gender matched healthy controls. RESULTS: Compared to healthy controls, attenuation of skin flushing at low niacin concentrations was found only in schizophrenia patients, but not in first-degree relatives. CONCLUSION: While our results indicate niacin hyposensitivity as reliable biological marker in schizophrenia, they do not provide clear evidence for its heritability. Particularly, the results in adolescent schizophrenia patients are suggestive for the perception of attenuated niacin flushing as secondary to the pathophysiology at the onset of schizophrenic illness, namely increased oxidative stress, alterations of unspecific immune-response or inflammation-like processes.     

The topical niacin sensitivity test: an inter- and intra-rater reliability study in healthy controls

Topical application of nicotinic acid results in erythema, and in some cases oedema of the skin, supporting a strong relationship between niacin sensitivity and prostaglandin D2. The aim of this study was to examine the inter-rater and intra-rater reliability of a 12-min niacin sensitivity test in healthy adults. Three raters assessed the skin reaction of 12 volunteers, over 3-min intervals across four niacin concentrations (0.1, 0.01, 0.001, and 0.0001), and over six sessions. Inter-rater reliability estimates ranged from 0.85 to 0.97 for the total niacin sensitivity score. Similar inter-rater reliability estimates were found for niacin sensitivity ratings by concentration and time. Intra-rater reliability estimates ranged from 0.63 to 0.93 for the total niacin sensitivity score. These data indicate that the 12-min topical niacin sensitivity test has excellent reliability.     

Niacin in cardiovascular prevention: mechanisms, efficacy, and safety

PURPOSE OF REVIEW: This review describes niacin's mechanism of action, efficacy in cardiovascular prevention, and safety. RECENT FINDINGS: A G-protein-coupled receptor [GPR109A/HM74A, mouse PUMA-G (protein upregulated in macrophages by interferon-gamma)] was found to mediate the antilipolytic effect of niacin via inhibition of adenylyl cyclase in adipocytes. The same receptor in skin Langerhans cells mediates the common flushing side effect. The endogenous ligand for the receptor may be beta-hydroxybutyrate. Among nine controlled clinical trials using niacin, mostly combined with other drugs, statistically significant positive impact on clinical or anatomic cardiovascular end-points was found in seven, which represents a remarkably consistent record of benefit. Although niacin induces insulin resistance, deterioration of glycemic control in diabetes is usually minor, and there is no evidence of increased incidence of new onset diabetes. Hepatic toxicity is common with higher doses of sustained-release niacin but rare with immediate-release and extended-release niacin at doses up to 2000 mg/day. Extended-release and immediate-release niacin do not substantially potentiate myopathic effects when given in combination with statins. SUMMARY: Recently developed understanding of the mechanisms, efficacy, and safety of niacin, along with progress in reducing the chief side effect of flushing, should enhance the use of this valuable agent for cardiovascular prevention.     

Investigation of TRAM flap oxygenation and perfusion by near-infrared reflection spectroscopy and color-coded duplex sonography

Near-infrared reflection spectroscopy, used experimentally for investigation of tissue hemoglobin content and oxygenation in various flaps, was tested in the pedicled transverse rectus abdominis musculocutaneous (TRAM) flap, chosen as a simple clinical model because of its well-known vascular anatomy and clinical relevance. The study intended to answer the following questions: Does the near-infrared reflection spectroscopy system used in this study measure tissue hemoglobin content and oxygenation in the superficial skin layers only, as proposed by the manufacturer? Is near-infrared reflection spectroscopy able to detect differences of tissue hemoglobin content and oxygenation in distinct zones of the TRAM flap skin before, early, and late after surgery? Does tissue hemoglobin content and oxygenation correspond to blood flow in the supplying superior epigastric artery and to clinical signs of TRAM flap perfusion and viability? In 11 patients, tissue hemoglobin content and oxygenation in the lower abdomen/TRAM flap, mastectomy skin flap, and contralateral breast were measured by a new near-infrared reflection spectroscopy system preoperatively, early postoperatively, and late postoperatively. Simultaneously, systolic peak flow in the ipsilateral superior epigastric artery was obtained by color-coded duplex sonography. Routine clinical monitoring was performed throughout the early postoperative period. Tissue hemoglobin content and oxygenation in the lower abdomen, mastectomy skin flap, and contralateral breast were similar before surgery but varied considerably between different patients. There were no significant differences among preoperative, early postoperative, and late postoperative values of tissue hemoglobin content and oxygenation in the mastectomy skin flap and contralateral breast. However, near-infrared reflection spectroscopy measurements of the TRAM flap revealed significant differences between preoperative and early postoperative values of tissue hemoglobin content and oxygenation and among zones I, II, and III early after surgery. Tissue hemoglobin content in the TRAM flap skin increased and oxygenation decreased early after surgery. Near-infrared reflection spectroscopy values corresponded to clinical signs of venous congestion predominantly in zone III. Late postoperative return of hemoglobin content and oxygenation in the TRAM flap toward preoperative values can be attributed to improved venous return by reversed flow across regurgitant valves and development of collateral circulation. Finally, there was a significant increase of systolic peak flow in the ipsilateral superior epigastric artery early after surgery. This could be related to the opening of small-caliber choke arteries between the superior and deep inferior epigastric arteries following ligation of the dominant deep inferior epigastric artery and TRAM flap transfer to the chest. Systolic peak flow returned to preoperative values late after surgery. The near-infrared reflection spectroscopy system used in this study appeared to measure hemoglobin content and oxygenation in the superficial skin layers only. Near-infrared reflection spectroscopy was able to detect differences of tissue hemoglobin content and oxygenation in the TRAM flap between preoperative and postoperative measurements and between distinct zones of the TRAM flap early postoperatively. Postoperative changes in near-infrared reflection spectroscopy values corresponded to clinical observations and blood flow in the superior epigastric artery measured by color-coded duplex sonography. Further experience is needed before near-infrared reflection spectroscopy can be advocated for routine clinical flap monitoring.     

Niacin skin-flush response and electrodermal activity in patients with schizophrenia and healthy controls

Patients with schizophrenia have in different studies shown reduced niacin sensitivity and lower electrodermal activity (EDA) after auditory stimulation. Peripheral mediation of prostaglandins may have a physiological role in both responses. This motivates study of both niacin response and electrodermal responding in the same patients with schizophrenia. Thirty patients with schizophrenia and 17 controls were investigated with EDA and thereafter given 200mg niacin orally with continuous assessment of skin temperature. The patients showed a delayed temperature increase after niacin ingestion (P=0.002) and a higher frequency of electrodermal non-responding (P<0.05). Response/non-response for niacin correlated with EDA response/non-response in the patient group (P=0.009). The niacin test revealed a slower vasodilation reaction in the patients. The association between response patterns for the niacin test and EDA suggests that a common aberration in skin physiology may be of importance for both reactions in schizophrenia.     

Design and Characterization of an Adhesive Matrix Based on a Poly(Ethyl Acrylate, Methyl Methacrylate)

The main issue in the development of transdermal patches made of poly(ethyl acrylate, methyl methacrylate) (Eudragit NE 40D, PMM) is the shrinkage phenomenon during the spreading of the latex onto the release liner. To solve this problem, the latex is usually freeze-dried and then re-dissolved in an organic solvent (method 1). To simplify the production process, we prepared an adhesive matrix by adding to the commercial PMM latex a plasticizer and an additive (anti-shrinkage agent) that avoids the shrinkage of the water dispersion spread onto the release liner (method 2). In some cases the active ingredient itself, such as potassium diclofenac (DK) and nicotine (NT), works as anti-shrinkage agent. In this work, the effects of the preparation method, types and concentrations of the plasticizer (triacetin and tributyl citrate) on the adhesive properties of the transdermal patches were investigated. The adhesive properties of the prepared patch were determined by texture analysis, peel adhesion test and shear adhesion. The PMM/plasticizer interactions were evaluated by ATR-FTIR spectroscopy. Furthermore, the in vitro skin permeation profiles of DK and NT released from the patch were determined by Franz cell method. Generally speaking, the variables that mainly modify the adhesive properties are the concentration and type of the plasticizer. The skin permeation profiles of DK and NT from the patch prepared by method 2 overlapped with those obtained with the commercial products. The results underline that the PMM latex can be used conveniently in the development of transdermal patches.     

Relationship between the niacin skin flush response and essential fatty acids in schizophrenia

The skin flush response to niacin is selectively mediated by the release of vasodilatory prostaglandins from the skin. The normal skin flush response to niacin is attenuated in many individuals with schizophrenia (SCZ). This finding suggests abnormal prostaglandin signaling in SCZ. Since prostaglandins are derived from arachidonic acid (AA), the finding of an abnormal skin flush response is consistent with biochemical data suggesting relative depletion of AA, and other essential fatty acids (EFAs), in a substantial portion of people with SCZ. This paper will describe the mechanism of the skin flush response to niacin, and will review evidence that the response to niacin is abnormal in SCZ, that this abnormality is not related to psychotropic medications, and that it may be a marker of the EFA deficiency which has been documented to be present in many patients with SCZ.     

Tissue oxygenation and perfusion in inferior pedicle reduction mammaplasty by near-infrared reflection spectroscopy and color-coded duplex sonography

Near-infrared reflection spectroscopy has been used in various experimental and clinical settings to investigate tissue perfusion and oxygenation noninvasively. Its application in plastic surgery has only recently been reported. The current study used near-infrared reflection spectroscopy to monitor cutaneous microcirculation in breast skin flaps after inferior pedicle reduction mammaplasty. Thirty patients underwent bilateral reduction mammaplasty by a modified Robbins technique. Near-infrared reflection spectroscopy measurements were performed preoperatively and postoperatively at several defined positions of the breast. The reflection spectroscopy system was capable of detecting absolute values of total hemoglobin in milligrams per milliliter of tissue and tissue hemoglobin oxygen saturation in percent. Color-coded duplex sonography was used to visualize nutrient vessels of the inferior dermoglandular pedicle and to measure systolic peak flow in the arteries supplying the nipple-areola complex. Reflection spectroscopy values were examined for changes during the postoperative course. Reflection spectroscopy and duplex sonography values were analyzed for differences between patients with normal and compromised skin flap perfusion and wound healing, which was assessed clinically and by ultrasound. Preoperative reflection spectroscopy values demonstrated local, regional, and interindividual variations. Postoperatively, characteristic changes of tissue hemoglobin oxygen saturation and total hemoglobin were observed in all patients during the 2-week follow-up. Reflection spectroscopy values differed significantly between breast and nipple-areola skin. Tissue hemoglobin oxygen saturation was significantly lower, and total hemoglobin significantly higher, in patients with impaired wound healing compared with patients having normal wound healing. However, systolic peak flow in arteries of the inferior dermoglandular pedicle did not reveal differences between patients with impaired or normal wound healing of the nipple-areola complex. Near-infrared reflection spectroscopy allows the detection of hemoglobin content and oxygenation in skin flaps. Changes in tissue hemoglobin oxygen saturation and total hemoglobin reflect hemodynamic changes in skin flaps during normal and pathological wound healing. Because of considerable intraindividual and interindividual variations, trend values seem to be superior to single measurements. Although in this study, near-infrared reflection spectroscopy was capable of distinguishing between normal and impaired perfusion in skin flaps in a clinical model, its future implication may be the early detection of vascular compromise in free flaps.     

Comparing quantitative measures of erythema,pigmentation and skin response using reflectometry

We measured a number of pigmentation and skin response phenotypes in a sample of volunteers (n=397) living in State College, PA. The majority of this sample was composed of four groups based on stated ancestry: African-American, European-American, Hispanic and East Asian. Several measures of melanin concentration (L*, melanin index and adjusted melanin index) were estimated by diffuse reflectance spectroscopy and compared. The efficacy of these measures for assessing constitutive pigmentation and melanogenic dose-response was evaluated. Similarly, several measures of erythema (a*, erythema index and adjusted erythema index) were compared and evaluated in their efficacy in measuring erythema and erythemal dose-response. We show a high correspondence among all of the measures for the assessment of constitutive pigmentation and baseline erythema. However, our results demonstrate that evaluating melanogenic dose-response is highly dependent on the summary statistic used: while L* is a valid measure of constitutive pigmentation it is not an effective measure of melanogenic dose-response. Our results also confirm the use of a*, as it is shown to be highly correlated with the adjusted erythema index, a more advanced measure of erythema based on the apparent absorbance. Diffuse reflectance spectroscopy can be used to quantify the constitutive pigmentation, melanogenic dose-response at 7 d and erythemal dose-response at both 24 h and 7 d postexposure.     

Involvement of nitric oxide in UVB-induced pigmentation in guinea pig skin

Ultraviolet (UV) B irradiation evokes erythema and delayed pigmentation in skin, where a variety of toxic and modulating events are known to be involved. Nitric oxide (NO) is generated from L-arginine by NO synthases (NOS). Production of NO is enhanced in response to UVB-stimulation and has an important role in the development of erythema. NO has recently been demonstrated as a melanogen which stimulates melanocytes in vitro, however, no known in vivo data has been reported to support this finding. In this study, we investigated the contribution of NO with UV-induced pigmentation in an animal model using an NOS inhibitor. UVB-induced erythema in guinea pig skin was reduced when an NOS inhibitor, L-NAME (N-nitro-L-arginine methylester hydrochloride), was topically applied to the skin daily, beginning 3 days before UVB-irradiation. Delayed pigmentation and an increased number of DOPA-positive melanocytes in the skin were markedly suppressed by sequential daily treatment with L-NAME. Furthermore, melanin content 13 days after UVB-irradiation was significantly lower in skin treated with L-NAME than in the controls. In contrast, D-NAME (N-nitro-D-arginine methylester hydrochloride), an ineffective isomer of L-NAME, demonstrated no effect on these UV-induced skin responses. These results suggest that NO production may contribute to the regulation of UVB-induced pigmentation.     

Niacin skin test response in dyslexia

The niacin skin test reflects a flush and oedema owing to the production of prostaglandin D2 from arachidonic acid. A diminished response may indicate abnormalities in the phospholipid metabolism, which has been shown in schizophrenia. There is evidence that dyslexia might also involve phospholipid abnormalities, therefore we examined the skin response in 51 dyslexics and 45 controls. Four concentrations of aqueous methyl nicotinate were applied topically to the forearm. Flushing was rated using a seven-point scale at 3 min intervals over 21 min. Repeated measures ANOVA for the four concentrations across all seven time-points showed no significant effect of subject group, but when analyses were confined to the first 9 min, flushing was reduced in dyslexics. Significant group differences were also found for the lowest niacin concentration (0.0001M) across six out of seven time-points. The results indicate a slightly reduced and delayed response to niacin in dyslexia.     

Evanescent Field Based Photoacoustics: Optical Property Evaluation at Surfaces

Here, we present a protocol to estimate material and surface optical properties using the photoacoustic effect combined with total internal reflection. Optical property evaluation of thin films and the surfaces of bulk materials is an important step in understanding new optical material systems and their applications. The method presented can estimate thickness, refractive index, and use absorptive properties of materials for detection. This metrology system uses evanescent field-based photoacoustics (EFPA), a field of research based upon the interaction of an evanescent field with the photoacoustic effect. This interaction and its resulting family of techniques allow the technique to probe optical properties within a few hundred nanometers of the sample surface. This optical near field allows for the highly accurate estimation of material properties on the same scale as the field itself such as refractive index and film thickness. With the use of EFPA and its sub techniques such as total internal reflection photoacoustic spectroscopy (TIRPAS) and optical tunneling photoacoustic spectroscopy (OTPAS), it is possible to evaluate a material at the nanoscale in a consolidated instrument without the need for many instruments and experiments that may be cost prohibitive.     

Comparing Quantitative Measures of Erythema,Pigmentation and Skin Response using Reflectometry

We measured a number of pigmentation and skin response phenotypes in a sample of volunteers (n=397) living in State College, PA. The majority of this sample was composed of four groups based on stated ancestry: African‐American, European‐American, Hispanic and East Asian. Several measures of melanin concentration (L*, melanin index and adjusted melanin index) were estimated by diffuse reflectance spectroscopy and compared. The efficacy of these measures for assessing constitutive pigmentation and melanogenic dose–response was evaluated. Similarly, several measures of erythema (a*, erythema index and adjusted erythema index) were compared and evaluated in their efficacy in measuring erythema and erythemal dose–response. We show a high correspondence among all of the measures for the assessment of constitutive pigmentation and baseline erythema. However, our results demonstrate that evaluating melanogenic dose–response is highly dependent on the summary statistic used: while L* is a valid measure of constitutive pigmentation it is not an effective measure of melanogenic dose–response. Our results also confirm the use of a*, as it is shown to be highly correlated with the adjusted erythema index, a more advanced measure of erythema based on the apparent absorbance. Diffuse reflectance spectroscopy can be used to quantify the constitutive pigmentation, melanogenic dose–response at 7 d and erythemal dose–response at both 24 h and 7 d postexposure.     

Prevalence of positive atopy patch test in an unselected pediatric population

Background

In the latest decades, epidemiological studies on allergic disorders in children, including atopic dermatitis, rhinitis and asthma, demonstrated a continuous increase in prevalence. However, such studies are usually performed by questionnaires and, sometimes, by skin prick test or in vitro IgE tests, while the portion of allergy sustained by the cell-mediated mechanism is neglected, because the essential test, i.e. the atopy patch test is not performed.

Methods

This cross-sectional survey studied by a specific questionnaire, skin prick test and atopy patch test, an unselected population, represented by the entire scholastic population attending a Primary school and a Junior Secondary school in the rural town of San Marco in Lamis, 12.000 inhabitants (Puglia, Italy).

Results

Among the 456 subjects included, 78 (17.1 %) had a positive skin prick test and 57 (12.5 %) had a positive atopy patch test. In particular, 13.4 % of subjects were positive only to skin prick test and 8.8 % were positive only to atopy patch test. The allergen most frequently positive was the house dust mite, with 41 positive results to skin prick test and 55 to atopy patch test, while for pollen positive results concerned almost exclusively the skin prick test.

Conclusions

This survey on an unselected population of children detected a prevalence of positive results to atopy patch test not so distant from the positive results to skin prick test, and in 8.8 % of subjects the atopy patch test was the only positive test. This would suggest to add the atopy patch test in future epidemiological studies on allergy, in order to avoid to overlook the not negligible portion of patients with T-cell-mediated allergy.     

Histoplasmosis in Montreal During the Fall of 1963, with Observations on Erythema Multiforme

Although Montreal is in an endemic area, significant clinical histoplasmosis with systemic manifestations has been, until recently, infrequently diagnosed. However, since the autumn of 1963, 31 cases of clinically significant histoplasmosis have been seen by the authors. These were divided into two groups: (1) patients in whom the diagnosis was established on the basis of histological and/or cultural demonstration of the fungus; (2) patients in whom the diagnosis was based on a positive histoplasmin skin test, a complement fixation antibody titre of 1:32 or greater and compatible clinical and radiological findings. An additional group of 11 patients who presented with erythema multiforme was investigated and a heretofore unrecognized relationship between histoplasmosis and erythema multiforme was established.     

Minimal Erythema Dose (MED) Testing

Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual''s skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual''s skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.     

Dermal carotenoid measurements via pressure mediated reflection spectroscopy

We describe a reflection‐based method for the quantitative detection of carotenoid antioxidants in living human skin. The skin tissue site of interest is illuminated with broad‐band white light spanning the spectral range from 350–850 nm and the spectral composition of the diffusively reflected light is analyzed in real time. Topical pressure is applied to temporarily squeeze blood out of the illuminated tissue volume. In this way the influence of oxy‐hemoglobin on the reflection spectra is effectively reduced. After a short optical clearing time the carotenoid absorption becomes easily discernable in a 460–500 nm spectral window and its optical density can be calculated with high accuracy. Our empirical methodology provides a non‐invasive rapid determination of skin carotenoid levels, can be used to monitor skin carotenoid concentration changes over time in response to carotenoid containing natural or supplemental diets, and is easily adaptable for applications in clinical and field settings. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Ultraviolet radiation-induced erythema in human skin

We have evaluated UVR-induced erythema in previously unexposed buttock skin of volunteers of skin types I, II, III, and IV. Studies were done with solar-simulated radiation (SSR), UVB, and UVAI and we determined the just perceptible minimal erythema dose (MED) and, in some cases, quantified erythema with a reflectance device. The results show that there is a trend for increased SSR MED with skin type, with the MED of skin type IV being approximately twice that of skin type I, a smaller difference than one might have expected. However, there is a very considerable overlap of MED between skin types which shows that MED is a very poor indictor of skin type. Quantitative dose-response and time course studies with SSR and UVAI showed broadly similar responses when comparable MED-based exposures were given. We used our data to test the new concept of the standard erythema dose (SED) with two different erythema action spectra, and confirmed that the SED approach works with the different UVR sources that we studied.     

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice.

Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115-0.23 J/cm2 results after 24-48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-alpha-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40-55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel non-invasive technique not previously reported for this purpose--magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p less than 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p less than 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p less than 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the irradiation has stopped, by a derivative of d-alpha-tocopherol which is stable to autooxidation.