bluuebunny/crossref_metadata_2025 huggingface dataset:
The central and renal hemodynamic effects of amino acid infusion in the study of renal reserve in the baboon
Authors: Easterling Thomas R. , Van Hook James , Roberts Bryan , Koerker Donna
Published: September 2011

Abstract: Normal human renal function is characterized by a large renal reserve. Recruitment of this reserve is a compensatory and pathological response to renal injury. This study was designed to assess the renal reserve and central hemodynamics of young female baboons and, in doing so, the appropriateness of the use of these animals in a model of human renal disease. Eight female baboons completed the protocol. PAH and inulin clearances were measured before and after an amino acid infusion. Central hemodynamics were measured with arterial and pulmonary artery catheters. Effective renal plasma flow and glomerular filtration rate increased by 42%% after amino acid infusion (P = .025). Expansion of renal function was not consistent among individual baboons; two of the eight animals did not demonstrate renal reserve. Central hemodynamics were unaffected by the protocol.
Longitudinal analysis of behavioral, neurophysiological, viral and immunological effects of SIV infection in rhesus monkeys
Authors: Gold Lisa H. , Fox Howard S. , Henriksen Steven J. , Buchmeier Michael J. , Weed Michael R. , Taffe Michael A. , Huitrón‐Resendiz Salvador , Horn Thomas F.W. , Bloom Floyd E.
Published: September 2011

Abstract:A model is proposed in which a neurovirulent, microglial‐passaged, simian immunodeficiency virus (SIV) is used to produce central nervous system (CNS) pathology and behavioral deficits in rhesus monkeys reminiscent of those seen in humans infected with human immunodeficiency virus (HIV). The time course of disease progression was characterized by using functional measures of cognition and motor skill, as well as neurophysiologic monitoring. Concomitant assessment of immunological and virological parameters illustrated correspondence between impaired behavioral performance and viral pathogenesis. Convergent results were obtained from neuropathological findings indicative of significant CNS disease. In ongoing studies, this SIV model is being used to explore the behavioral sequelae of immunodeficiency virus infection, the viral and host factors leading to neurologic dysfunction, and to begin testing potential therapeutic agents.
Expression and in vitro evaluation of rhesus macaque wild type (wt) and modified CC chemokines
Authors: Bostik Pavel , Villinger Francois , Brice Gary T. , Chikkala Nathaniel F. , Brar Sukhdev S. , Cruikshank William W. , Adams Jonathan W. , Hillyer Christopher D. , Ansari Aftab A.
Published: September 2011

Abstract: Several human CC chemokines have been shown to inhibit HIV/SIV infection in vitro, providing the rationale for their potential use in vivo. However, because of their inherent physiological effect, such chemokines are reasoned to be of limited therapeutic value due to potential side effects. The knowledge that amino terminus modified or deleted human RANTES retains its receptor binding properties but loses its signaling properties has provided a means to use such modified chemokines in vivo for possible therapeutic benefits. In efforts to test the efficacy of such modified chemokines, our laboratory has cloned, sequenced, and prepared recombinant forms of wild‐type (wt) and amino‐terminus modified rhesus macaque chemokines MIP‐1α, MIP‐1β, and RANTES. These sets of chemokines were tested for their potential to inhibit SIV infection and induce signaling. The data showed that whereas wt chemokines retained both virus inhibitory and signaling functions, corresponding aminoterminus modified chemokines only showed virus inhibitory effects without detectable signaling effects. Such reagents will be valuable for evaluation of their therapeutic potential in vivo, either alone or as adjuncts to other chemotherapeutic drugs.
Dendritic cells from skin and blood of macaques both promote SIV replication with T cells from different anatomical sites
Authors: Ignatius Ralf , Isdell Frank , O'Doherty Una , Pope Melissa
Published: September 2011

Abstract: The SIV‐macaque system offers the opportunity to study the pathogenesis and immune aspects of a primate retroviral infection in which immunodeficiency also develops, much like HIV infection in humans. Since it is known that human dendritic cells (DCs) are involved in HIV replication, mature cytokine‐generated DCs obtained from precursors in the blood and skin‐derived DCs were isolated from healthy rhesus macaques and compared with respect to their ability to support SIV infection. Here, it is shown for both skin‐ and blood‐derived DCs that i) virus production depends on both DCs and T cells, ii) this occurs similarly with T cells from blood, skin, spleen, or lymph nodes, and iii) DCs can transmit virus equally to syngeneic and allogeneic T cells. No differences between DCs from skin or blood were observed. Therefore, the easily accessible blood‐derived DCs of macaques provide an appropriate population to study the role of DCs in immunodeficiency virus infection.
Histopathological studies of senile plaques and cerebral amyloidosis in cynomolgus monkeys
Authors: Nakamura Shin'ichiro , Nakayama Hiroyuki , Goto Naoaki , Ono Fumiko , Sakakibara Ippei , Yoshikawa Yasuhiro
Published: September 2011

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA), pathological hallmarks of Alzheimer's disease, have not been thoroughly investigated histopathologically in nonhuman primates. To determine the onset age and histopathological characteristics of SPs and CAA, we examined the brains of 64 cynomolgus monkeys (Macaca fascicularis) from 2 to 35 years old. Mature (classical and primitive) plaques appeared in 16 out of 25 monkeys that were >20 years old. Moreover, mature plaques were observed more frequently than diffuse plaques and were located in the temporal cortex of the superior or inferior gyri and amygdala. Diffuse plaques in contrast to mature plaques did not show definite tendencies in onset age and distribution. CAA appeared in more than 22‐year‐old monkeys in 10 out of 16 animals and was frequently observed in capillaries and often found adjoining mature plaques. During immunohistochemical examination, an antiserum for amyloid β protein (Aβ) 1–40 could detect all SPs, whereas a monoclonal antibody for Aβ 8–17 could not detect any diffuse plaques and only one third of the primitive plaques. As for CAA, the polyclonal antiserum was more sensitive than the monoclonal antibody. The present study describes the histopathological features of SPs and CAA in old cynomolgus monkeys.
Biochemistry and haematology values for the baboon (Papio hamadryas): The effects of sex, growth, development and age
Authors: Harewood Winthrop J. , Gillin Adrian , Hennessy Annemarie , Armistead Jeff , Horvath John S. , Tiller David J.
Published: September 2011

Abstract: A retrospective study evaluated the influence of sex and age on plasma biochemistry and haematology parameters in a captive‐bred colony of baboons. Over 1,140 ETDA and heparin blood samples were obtained from 160 clinically normal baboons between the ages of 11 months and 11 years. Data for these blood tests were analysed for the effects of sex, age and sex‐age interactions. Sex, age and sex‐age interactions were detected for many plasma biochemistry and haematological parameters. The reference range values for platelets, white‐blood cells and mean corpuscular volume and plasma chloride, glucose, total protein and iron were higher (P < 0.01) and red blood cell, plasma sodium, potassium, total CO2, creatinine, urea, total bilirubin, albumin, alkaline phosphate, gamma glutamyl transpeptidase and phosphate were lower (P < 0.01) in the female compared to the male population. Sex‐age interactions (P < 0.05) were seen with haemoglobin, white blood cells, haematocrit, mean corpuscular volume, sodium, creatinine, urea, calcium, phosphate, total bilirubin, total protein alkaline phosphatase, the liver enzymes and triglycerides. Plasma alkaline phosphatase was highest (> 800 μ/l) in young juveniles of both sexes; creatinine was higher in older (> 4 years) compared to younger baboons of the same sex (P < 0.05). Plasma cholesterol and triglycerides were greater (P < 0.01) in young baboons compared to older animals.
Sequence conservation of repeat 3 region of the gene coding for the 15 kDa polyprotein within human and simian Loa loa*
Authors: Toure Fousseyni S. , Leroy Eric M. , Mavoungou Elie , Egwang Thomas G.
Published: September 2011

Abstract: The human and simian strains of Loa loa microfilariae are morphologically identical even though their periodicities vary. When using primate models (Mandrillus sphinx) of human loaisis for vaccination trials, the absence of any ongoing simian L. loa infection must be demonstrated. Nested primers derived from a human strain of L. loa (targeted on the repeat 3 region of the gene encoding the 15 kDa polyprotein; 15r3) amplified at 366 bp sequence from simian L. loa genomic DNA and blood lysates from mandrills infected with simian L. loa. This nested‐PCR assay has been tested on 12 amicrofilaremic (AMF) mandrills (without filarial microfilariae) and was positive in four mandrills. The nested‐PCR product derived from simian L. loa genomic DNA and from three of four AMF mandrills has been sequenced. No difference was observed between the four sequences, which, in addition, were 99.18% identical to the 15r3 of human L. loa. Therefore, the 15r3 sequence is conserved within human and simian L. loa. These results suggest that the four PCR‐positive mandrills without circulating microfilariae had occult simian L. loa infections. The study demonstrates the ability of a nested‐PCR assay to identify animals naturally infected with simian L. loa.
Comparison of kidney weight and volume to selected anatomical parameters in the adult female rhesus monkey (Macaca mulatta)
Authors: Hill Lori R. , Hess Kenneth R. , Stephens L. Clifton , Tinkey Peggy T. , Price Roger E.
Published: September 2011

Abstract:In this study, the normal distribution of renal weight and volume was determined and the correlation between the weight and volume and various skeletal measurements taken from radiographs and at necropsy was assessed. Values from 136 female monkeys with complete data (including all bone, radiographic, and kidney measurements) were analyzed. The mean kidney weight was 13 g with a standard deviation (SD) of 2 g. The mean kidney volume was 12 ml, SD 2 ml. The estimation of kidney weight and volume from bone length, age, or body weight was not reliable according to statistical analysis of our data. We did find that all apparently normal adult female rhesus monkeys typically have similar sized kidneys. This information is useful in that it reduces concerns about consistency in experimental subjects.
Perineal swelling during pregnancy in common chimpanzees and puerperal pathology
Authors: Dahl Jeremy F.
Published: September 2011

Abstract: Perineal swelling during pregnancy in captive common chimpanzees (Pan troglodytes) was studied to examine if the swelling pattern is consistent with known fluctuations in estrogens and progesterone and to test associations between reduced swelling and pathological outcome. Analyses of swelling during 107 pregnancies with a variety of outcomes revealed that a majority of swelling patterns fit an endocrinological model closely, but that a small minority (6.6%) from low parity mothers had exaggerated and extended swelling, suggesting an altered sensitivity of the swelling to steroids. Disregarding this extreme minority, swelling was found to be significantly reduced from that of normal outcome pregnancies for sub‐groups with varying degrees of maternal incompetence, neonatal fatality, and stillbirth. This reduction was most marked for pregnancies in nursery‐reared mothers. Given the validity of the correspondence between swelling patterns and steroid concentrations, lower estrogen concentrations are implicated in the etiology of the puerperal pathologies seen. That steroid hormone concentrations during pregnancy may influence maternal behavior in apes provides a clue to the etiology of post‐partum depression in women.
Natural infection of chimpanzees with new lentiviruses related to HIV‐1/SIVcpz
Authors: Takehisa Jun , Bikandou Blaise , Ido Eiji , Mboudjeka Innocent , M'Vouenze Reine , Nzoukoudi Marie‐Yvonne , Harada Yosuke , Yamaguchi‐Kabata Yumi , Miura Tomoyuki , M'Pandi Michel , Parra Henri Jopseph , M'Pelé Pierre , Hayami Masanori
Published: September 2011

Abstract: To determine newly identified lentiviruses, termed simian immunodeficiency virus (SIV)cpz97CG4 and SIVcpz97CG6, from two wild‐captured juvenile brother chimpanzees in the Republic of Congo, subgenomic pol (integrase, 288 bp), 5′tat/rev‐env C1 (including vpu, 354 bp) and env (C2‐C4, 544 bp) gene fragments were amplified and sequenced. The analysis revealed significantly discordant phylogenetic positions of SIVcpz97CG in each genomic region. In the trees derived from partial env sequences (V3), both SIVcpz strains clustered in human immunodeficiency virus type 1 (HIV‐1) subtype A. However, in the trees derived from partial pol (integrase) and 5′tat/rev‐env C1 (including vpu) sequences, they clustered independently from any of the known HIV‐1 subtypes. Especially, in the 5′tat/rev‐vpu tree, they branched before the root of HIV‐1 group M. These findings suggest that these Congolese SIVcpz genomes are mosaic, probably due to a recombinational event in the recent past, and it provides evidence for a rather recently occurring cross‐species transmission between humans and chimpanzees.
The effect of porphyrin and radiation on ferrochelatase and 5‐aminolevulinic acid synthase in epidermal cells
Authors: He D. , Behar S. , Nomura N. , Sassa S. , Taketani S. , Lim H. W.
Published: September 2011

The effects of ultraviolet A (UVA) and blue light on ferrochelatase protein, and its mRNA level, in 5‐aminolevulinic acid (ALA)‐loaded A431 cells was evaluated. Western blot analysis of ferrochelatase protein showed a protein band of 43 kDa. There was a decrease in the protein concentration 24 h and 48 h after irradiation of these cells. In contrast, as judged by Northern blot analysis, there was no change in ferorchelatase mRNA level. Measurement of ALA synthase activity showed an ALA dose‐dependent but radiation‐independent decrease of enzyme activity, suggesting an end‐product feedback inhibition. Since reactive oxygen species generated by porphyrin‐induced photochemical reaction may be involved in the decrease in ferrochelatase protein, the effect of scavengers of reactive oxygen species was evaluated by measuring porphyrin accumulation in irradiated, ALA‐loaded A431 cells. Porphyrin accumulation was significantly decreased in the presence of singlet oxygen scavenger sodium azide (0.05 mM, 40.6% suppression) or hydroxyl radical scavenger mannitol (5.0 mM, 45.0% suppression). These data suggest that the photochemical reaction induced by porphyrin and irradiation resulted in a decrease in ferrochelatase protein content, but had no effect on ferrochelatase mRNA level nor on ALA synthase activity. The decrease in protein was partly mediated by the reactive oxygen species.
Phototoxic and photoprotective effects of topical isothipendyl
Authors: Moreau A. , Dompmartin A. , Dubreuil A. , Leroy D.
Published: September 2011

Isothipendyl, an H1‐receptor antagonist, is an antihistamince used as an antiallergic drug. Its molecular structure is close to the phenothiazines, but it has different photobiological properties. Like phenothiazines, isothipendyl is phototoxic with ultraviolet A (UVA) but it reduces the erythema response to UVB radiation. Isothipendyl seems to have the same protective properties as a sunscreen because its UVB protective properties are effective only if the substance is applied prior to exposure.
5‐Methoxypsoralen photoadduct formation: conversion of monoadducts to crosslinks
Authors: Amici L. A. , Gasparro F. P.
Published: September 2011

5‐Methoxypsoralen is often substituted for 8‐methoxypsoralen in the photochemotherapy of psoriasis even though the nature of the resulting photadducts in cellular DNA has not been determined. A recent molecular mechanics study with a model oligonucleotide predicted that intercalated 5‐methoxypsoralen molecules would tend to favor the preferential formation of 3,4‐monoadducts. Such a result would be contrary to the photoadduct patterns observed with other psoralens. In this study we show that 5‐methoxypsoralen photoadducts formation is, in fact, very similar to that for other psoralens, i.e., the primary photoadduct is the 4′,5′‐monoadduct which can be quantitatively converted to crosslink.
Sun protection and sunscreen use after surgical treatment of basal cell carcinoma
Authors: Harth Y. , Ulman Y. , Peled I. , Friedman‐Birnbaum R.
Published: September 2011

Sixty‐three patients (mean age 54± 9 years) who were treated for a basal cell carcinoma (BCC) and 54 control subjects (mean age 51± 11 years) filled out detailed questionnaires on their sun exposure and sun protection habits. Patients were given the questionnaires at least 1 year after their skin tumors had been excised. Differences between patients and controls in mean age, gender, Fitzpatrick's skin type and eye and hair color were statistically nonsignificant. The level of education was high in both patients and controls (mean of 13.4± 3.1 school years). Differences in education were statistically nonsignificant. We found that both patients and controls were knowledgeable about the role of sunscreens in preventing skin tumors (79% and 83% respectively) and in preventing sun‐induced aging (90% and 85% respectively). Significantly more patients used sunscreens regularly (64%) compared with controls (36%). Nevertheless, our data show no statistically significant differences between the sun exposure habits of the patients previously treated for BCC and controls. Moreover, we found that, although 82% of the patients declared that they tried to avoid sun, only 49% regularly wore hats or shirts with long sleeves in the summer (19%). Sixty‐two percent of the patients used two or fewer bottles of sunscreens per year, which is inadequate for effective year‐round sun protection. In addition, we found that many patients, as well as the controls, applied sunscreens only once a day (57% and 46% respectively), did not reapply after swimming (58%, 74% respectively), and did not use sunscreens in the winter (49%, 61%). Our data show that, although patients after BCC removal have a significantly higher sunscreen use compared with controls, the amount and methods of application are less than adequate. Moreover, other simpler methods to prevent photodamage, such as simple sun avoidance or the use of protective clothing, are often neglected.
Characterization of sunburn cells after exposure to ultraviolet light
Authors: Bayerl C. , Taake S. , Moll I. , Jung E. G.
Published: September 2011

Sunburn cells (SBCs) appear in the epidermis shortly after acute UV damage, especially after exposure to UVB light. As yet, the mode of their formation remains to be satisfactorily elucidated. In order to characterize these cells, the expression of various markers of epidermal differentiation following UV exposure was investigated using immunhistochemical procedures. These were applied to paraffin‐embedded (microwave technique) and frozen specimens of human skin 24 h after irradiation with 4 times the minimal erythema doses(MED). Normal nonirradiated skin without irradiation served as the control. We used a battery of antibodies directed against the following: cytokeratins (CKs) 5, 10, 17, and 19, actin, cell‐adhesion proteins (desmoplakins, desmogleins), markers of terminal epidermal differentiation (filaggrin, involucrin and loricrin), markers of proliferation (PCNA, MIB, K6,16), a marker of endocytosis (clathrin) and markers of cell growth, (transforming growth factor [TGF‐α]) and B‐cell leukemia/lymphoma‐2 [bcl‐2]. After UV irradiation it was found that CK 5, which is typically confined to basal keratinocytes, was also expressed in suprabasal keratinocytes. The CKs 1 and 10/11 exhibit a normal suprabasal localization, but suprisingly, SBCs were negative for these CKs. Although CK 6,16, and 17 are not usually found in normal epidermis, UVB exposure induced their expression in suprabasal keratinocytes, but again failed to elicit their expression in SBCs. Antibodies specific for markers of late epidermal differentiation (filaggrin, involucrin and loricrin), cell‐junction proteins (desmogleins, desmoplakins), proliferation (PCNA and MIB), and endocytosis (clathrin) also failed to produce positive staining of SBCs. Even though TGF‐α immunoreactivity became detectable in most keratinocytes after UV exposure, this was not the case for SBCs. The number of basally located dendritic cells, most probably melanocytes, exhibiting bcl‐2 staining was markedly reduced 6 and 12 h after irradiation as compared with normal skin. SBCs do not express any late differentiation markers, but they do contain proteins typical of basal keratinocytes (CK 5). It can be concluded that SBCs do not develop beyond a more basal‐like differentiation pattern, probably as a result of cell death and migration through the epidermis.
Cutaneous carcinoma and PUVA lentigines in Thai patients treated with oral PUVA
Authors: Gritiyarangsan P. , Sindhavananda J. , Rungrairatanaroj P. , Kullavanijaya P.
Published: September 2011

A total of 113 Thai patients who were treated with oral PUVA from 1979 to 1992 were examined for long‐term cutaneous side effects of PUVA. Two psoriatic patients developed PUVA keratosis on non‐sun‐exposed areas. Both were skin type IV and had had phototherapy with UVB and sunlight previously. The total doses of UVA were 909 J/cm2 and 242 J/cm2 respectively. One psoriatic patient developed Bowen's disease. He had had a cumulative dose of UVA 2207 J/cm2. He also had a past history of arsenic intake and phototherapy with UVB and sunlight. PUVA lentigines were seen in 58 patients (51.4%). It was associated with older age at starting PUVA, higher cumulative UVA dose and greater number of PUVA treatment. This study suggests that previous exposure to other risk factors is important for inducing skin cancer in populations with skin phototype III, IV and V treated with oral PUVA.
Treatment with topical khellin in combination with ultraviolet A or solar‐simulated radiation is carcinogenic to lightly pigmented hairless mice
Authors: Bech‐Thomsen N. , Wulf H. C.
Published: September 2011

Khellin is used together with either UVA irradiation or sun exposure in the treatment of vitiligo. The purpose of this study was to investigate the carcinogenic effect of topically applied khellin together with UVA or solar simulated radiation (SSR) in lightly pigmented C3H/Tif mice. For comparison purposes a 0.1% 8‐methoxypsoralen (8‐MOP) cream was also tested in combination with SSR. Fifty μ1*** of a 5% khellin cream, a 0.1% 8‐MOP cream, or a cream without active substances were spread uniformly on the back of the mice 30 minutes before UVA or SSR irradiation. All mice were irradiated 3 times a week until age or skin tumor development necessitated killing. Treatment with topical khellin and UVA irradiation was carcinogenic to lightly pigmented hairless mice, time to 50% of the mice had developed one tumor (t50) was 507 days. This indicates that the combination of topical khellin and UVA radiation, formerly expected to be rather innocuous, is carcinogenic to mice. Also the combination of khellin and SSR (t50 = 268 days) enhanced skin tumor development significantly compared with control cream and SSR (t50 = 330 days), P<0.05. In addition, the combination of khellin and SSR was found to have the same carcinogenic effect as treatment with 0.1% 8‐MOP and SSR (t50 = 262 days). This study shows that topically applied khellin increases the carcinogenic effect of both UVA and sunlight.
Enhanced proliferation and collagen synthesis of human dermal fibroblasts in chronically photodamaged skin
Authors: Chung J. H. , Youn S. H. , Kwon O. S. , Eun H. C. , Kim K. H. , Park K. C. , Cho K. H. , Youn J. I.
Published: September 2011

Cutaneous aging can be divided into intrinsic aging and photoaging. We investigated the influence of aging and photoaging on the proliferation and collagen synthesis of human dermal fibroblasts cultured 3‐dimensionally in a collagen gel. We examined 11 human dermal fibroblast cell lines cultured from 3 newborn skins (1 day old), and both exposed and unexposed skin from 4 elderly volunteers (60, 60, 73, 76 years old), respectively. Newborn fibroblasts actively proliferated within the attached collagen gels compared with the elderly cell lines. Within the attached collagen gels in the presence of 10% fetal calf serum (FCS), the fibroblasts from exposed skin proliferated rapidly compared with fibroblasts from unexposed skin from the same individuals. In collagen gel and monolayer cultures with 1% FCS, the percentage of collagen synthesized by photoaged and aged fibroblasts decreased significantly compared with that by newborn fibroblasts. When the fibroblasts were cultured three dimensionally in attached collagen gels in the presence of 1% FCS, the relative levels of collagen synthesis by cultured fibroblasts from photoaged skin were increased significantly compared with those of aged skin fibroblasts from the same individuals. These results suggest that fibroblasts of exposed skin may be more active than those of unexposed skin and that the three‐dimensional culture of fibroblast can be used as a model to investigate the influence of aging and photoaging on cell functions.
Enzyme therapy of xeroderma pigmentosum: safety and efficacy testing of T4N5 liposome lotion containing a prokaryotic DNA repair enzyme
Authors: Yarosh D. , Klein J. , Kibitel J. , Alas L. , O'Connor A. , Cummings B. , Grab D. , Gerstein D. , Gilchrest B. A. , Ichihashi M. , Ogoshi M. , Ueda M. , Fernandez V. , Chadwick C. , Potten C. S. , Proby C. M. , Young A. R. , Hawk J. L. M.
Published: September 2011

Xeroderma pigmentosum (XP) is a rare genetic disease in which patients are defective in DNA repair and are extremely sensitive to solar UV radiation exposure. A new treatment approach was tested in these patients, in which a prokaryotic DNA repair enzyme specific for UV‐induced DNA damage was delivered into the skin by means of topically applied liposomes to supplement the deficient activity. Acute and chronic safety testing in both mice and humans showed neither adverse reactions nor significant changes in serum chemistry or in skin histology. The skin of XP patients treated with the DNA repair liposomes had fewer cyclobutylpyrimidine dimers in DNA and showed less erythema than did control sites. The results encourage further clinical testing of this new enzyme therapy approach.
Suppressive effect of ultraviolet B radiation on contact sensitization in mice. II. Systemic immunosuppression is modulated by ultraviolet irradiation and hapten application
Authors: Miyauchi‐Hashimoto H. , Horio T.
Published: September 2011

Irradiation of mice with ultraviolet B (UVB) can suppress contact hypersensitivity “systemically”, even if hapten is applied to the non‐irradiated skin site. We previously reported the factors influencing UVB‐induced “local” immunosuppression. To obtain the most effective systemic immunosuppression, we further investigated the effect of the following factors on contact hypersensitivity to dinitrofluorobenzene (DNFB): UVB dose, dividing exposure, timing of sensitization after irradiation, area of exposure, hapten concentration, age, and genetic basis. The suppression was enhanced by increasing UVB dose. When 1 J/cm2 of UVB was exposed, 4 daily divided exposures (0.25 J/cm2x4) was more suppressive than a single (1 J/cm2x1) or double divided (0.5 J/cm2x2) exposure. Five or 10 day intervals between irradiation and sensitization induced stronger suppression than 1 or 3 day intervals. When the total energy (Joule, J) was kept constant, the exposure of low dose‐UVB to a large area (0.5 J/ cm2 × 16.45 cm2) suppressed contact hypersensitivity more strongly than did high dose‐UVB to a small area (2 J/cm2x4.11 cm2). When 25 ml of DNFB solution was applied, high concentration induced lower suppression. The stronger suppression was most prominant in the young (7 week) than in the old (22 week) mice. No difference was found in the systemic immunosuppression between C3H/HeN and Balb/c mice. These results suggest that not only UVB dose but also various factors should be taken into consideration to effectively induce systemic immunosuppression.
UVB irradiation decreases the magnitude of the Th1 response to hapten but does not increase the Th2 response
Authors: Saijo S. , Kodari E. , Kripke M. L. , Strickland F. M.
Published: September 2011

Exposure of murine skin to low doses of ultraviolet‐B (UVB) radiation before sensitization with hapten reduces the ability of antigen presenting cells (APC) in the draining lymph nodes to initiate contact hypersensitivity responses in vivo and results in the induction of hapten‐specific suppressor T cells. In the present study, we tested the hypothesis that exposure of skin to UVB radiation suppresses T cell responses to hapten in vivo by altering the functions of APC, resulting in decreased stimulation of Th1 lymphocytes, which mediate contact hypersensitivity responses, and preferential activation of Th2 cells. C3H/HeN mice were exposed to either a single 2 kJ/m2 dose of UVB or to 400 J/m2 of UVB daily from FS40 sunlamps for four consecutive days and sensitized with fluorescein isothiocyanate on UV‐irradiated skin. Draining lymph node cells were collected 18 h after sensitization and co‐cultured with nylon wool‐purified T cells from naive or fluorescein‐immunized mice. Unseparated lymph node cells or sorter‐purified fluorescein‐bearing APC from UV‐irradiated mice induced less T cell proliferation than APC from non‐UV‐exposed mice. Lymph node cells produced less Th1 and Th2‐associated cytokines, interferon‐gamma and interleukin‐4, respectively, in response to APC from UV‐irradiated animals compared with APC from unirradiated, fluorescein‐sensitized mice. Thus, low doses of UV radiation do not result in preferential stimulation of Th2 response in lymph nodes, and results from cloned cell lines may incompletely reflect T cell responses in vivo.
Interleukin‐15 expression by human endothelial cells: up‐regulation by ultraviolet B and psoralen plus ultraviolet A treatment
Authors: Mohamadzadeh M. , McGuire M. J. , Dougherty I. , Cruz P. D.
Published: September 2011

The purposes of the present study were to determine whether endothelial cells express IL‐15 and to evaluate effects of ultraviolet B (UVB) and 8‐methoxypsoralens plus UVA (PUVA) on such expression. Cultured human endothelial cells derived from dermis or umbilical veins were subjected to reverse transcriptase‐polymerase chain reaction (RT‐PCR) and immunoblot analyses for the detection of IL‐15 mRNA and protein, respectively. Both dermal and umbilical vein endothelial cells were shown to express IL‐15 mRNA and protein, and these markers were upregulated following UVB or PUVA treatment (but not by UVA or 8‐methoxypsoralens alone). Also using RT‐PCR, dermal and umbilical vein endothelial cells were shown to express IL‐2Rγc mRNA. These results expand the sources of IL‐15 in skin to include keratinocytes, dermal fibroblasts, and now endothelial cells. That IL‐15 from all three skin cells can be upregulated by UV treatment suggests a role for this cytokine in photosensitive disorders. Finally, the possibility of an autocrine effect of IL‐15 on endothelial cells is raised by the expression of IL‐2Rγc in these cells.
Porphyrin metabolism in hepatitis C infection
Authors: O'Reilly F. M. , Darby C. , Fogarty J. , O'Moore R. , Courtney M. G. , O'Connor J. , Kay E. W. , Leader M. , Fielding J. F. , Murphy G. M.
Published: September 2011

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti‐D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.
Phototoxicity to sulphonamide‐derived oral antidiabetics and diuretics: investigations in hairless mice
Authors: Selvaag E. , Thune P.
Published: September 2011

The oral antidiabetics glibenclamide, glipizide, glymidine, tolazamide and tolbutamide and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, furosemide, hydrochlorothiazide, hydroflumethiazide and trichlormethiazide were investigated for phototoxic effects in hairless mice. The back of the animals (hr/hr‐c3H/TifBom) was covered with Duoderm dressing, and at the site of two punched out holes 0.05 ml of the test substances at 0.25 mol/1 concentration and the solvent alone as control were injected intradermally, respectively. Both test and control sites were irradiated with 6–12 J/cm2 of longwave UVA light from a “Bluelight 2000” apparatus (Hönle, Martinsried, Germany). Skin reactions were read at 24 and 48 h. Compared to the solvent alone, all of the test substances induced reactions (necrosis or oedema) ‐ most frequently seen by macroscopic and histologic investigation and by measurements with a thickness gage. Injection of the test substance or solvent alone without or with subsequent UVA irradiation, as well as UVA alone, did not induce measurable skin changes in this model. Three oral antidiabetics and four diuretics, not yet described to induce photosensitivity in vitro nor in vivo, were detected as potential photosensitizers using our animal model.
Bath PUVA – an investigation of the distribution of trioxsalen (TMP) and 8‐methoxypsoralen (8‐MOP) in bathwater
Authors: Wainwright N. J. , MacLeod T. M. , Ferguson J.
Published: September 2011

Trioxsalen (TMP) bath PUVA avoids the side effects of nausea and head ache associated with oral 8‐methoxypsoralen (8‐MOP) treatment and allows shorter irradiation times that can be advantageous in some patients. However we noted that a number of patients developed unusual patterns of phototoxic burning. We thought that this was related to an uneven distribution of the TMP in the bathwater and for this reason, a study of bath water TMP concentrations achieved using different TMP preparations was undertaken. The distribution of 8‐MOP in an 8‐MOP bath was also measured for comparison. Our results confirm that an uneven distribution of TMP is achieved using TMP capsules or suspension and would explain our observed patterns of burning. With an ethanolic solution of TMP, or the commercial equivalent Tripsor, or with Puvasoralen‐8 (an 8‐MOP preparation), a homogeneous psoralen distribution is achieved, and they are therefore preferable for use in bath PUVA.
Use of dermal equivalent and skin equivalent models for identifying phototoxic compounds in vitro
Authors: Augustin C. , Collombel C. , Damour O.
Published: September 2011

Phototoxicity inducing in vivo photoirritation, a reversible inflammatory reaction of the skin after chemical contact and UVA radiation exposure, is increasingly observed as a side effect associated with the use of both cosmetics and systemic drugs. In order to systematically screen for the phototoxic potential of new compounds, we propose two three‐dimensional models suitable for in vitro testing: a dermal equivalent (DE) and a skin equivalent (SE) model. The DE model includes a collagen‐glycosaminoglycans‐chitosan porous matrix populated by normal human fibroblasts. The SE model is made by seeding normal human keratinocytes onto the DE, leading to a fully differentiated epidermis. The objectives of this pilot study are: 1) to compare the deleterious effects of UVA radiation on the two models and 2) to evaluate to what extent the in vitro results can predict the in vivo phototoxicity caused by well‐known photoirritant compounds, included in the COLIPA validation phototoxicity reference chemical list. Dilutions of thiourea, sulisobenzone, promethazine, chlorpromazine and tetracycline were applied (20 μl) onto DEs and SEs (n = 6) and incubated for 1 h (or 15 h) at 37°C. Irradiated samples received 3 J/cm2 UVA. The 24 h post‐irradiation residual cellular viability was measured using the MTT test on treated and untreated tissues and IL‐1α release measurement in collected SE culture media. A concordance in terms of photoirritant/non‐photoirritant was obtained between the in vivo data and the in vitro results, suggesting that the DE and the SE models could be integrated, after a complete validation study, into a protocol for in vitro testing of the photoirritant potential of new molecules.
Cyclosporin A therapy for severe solar urticaria
Authors: Edström D. W. , Ros A.‐M.
Published: September 2011

Solar urticaria is characterized by itching weals that occur a few minutes after exposure to visible or ultraviolet light. The symptoms may sometimes restrict normal daily life. Treatment is difficult in more severe cases. We describe one patient with solar urticaria who was successfully treated with cyclosporin A. The patient had first been treated with antihistamine, PUVA and chloroquine phosphate without effect. Cyclosporin was given in a dose of 4.5 mg/kg body weight/day. Photo testing before, during and after treatment showed a decreased light sensitivity to UVA, UVB and visible light during cyclosporin treatment compared with phototesting before therapy. The patient could be out in the sun for at least 1 h with minimal urticaria during cyclosporin therapy compared with only a few minutes previously. However, 1–2 weeks after cyclosporin therapy was discontinued, skin symptoms returned. Cyclosporin therapy is a possible treatment in severe cases of solar urticaria where other treatments have failed, especially in countries where treatment is necessary only for a few months during summer.
Photoprotective effect of calcipotriol upon skin photoreaction to UVA and UVB
Authors: Youn J. I. , Park B. S. , Chung J. H. , Lee J. H.
Published: September 2011

It has been shown that 1,25‐dihydroxyvitamin D3 has a photoprotective effect against UVB injury in mouse skin and cultured rat keratinocytes by induction of metallothionein (MT). Calcipotriol is a synthetic analogue of 1,25‐dihydroxyvitamin D3 with equipotent cell regulating properties, but with a lower risk of calcium‐related side effects. The aim of the present study was to see whether calcipotriol has a photoprotective property both in vitro and in vivo. We examined the effect of calcipotriol on UV‐induced damage of cultured human keratinocytes through a cell viability assay, and measurement of DNA synthesis by cultured keratinocytes, on UV‐induced damage of mouse skin and on minimal erythema dose (MED). We found that calcipotriol was protective against UVB‐induced reduction in DNA synthetic activity of cultured keratinocytes in relatively low doses (20 and 40 mJ/cm2) of UVB. With phototesting following application of calcipotriol, five subjects among 10 healthy volunteers and three among six psoriasis patients showed an increase in MED compared with the vehicle‐treated site. These findings imply that calcipotriol may be photoprotective and that more extensive studies with various doses of UV irradiation and modes of calcipotriol delivery are required.
Structural and biochemical basis for the UVB‐induced alterations in epidermal barrier function
Authors: Holleran W. M. , Uchida Y. , Halkier‐Sorensen L. , Haratake A. , Hara M. , Epstein J. H. , Elias P. M.
Published: September 2011

Ultraviolet light (UVR) induces a myriad of cutaneous changes, including delayed disruption of the permeability barrier with higher doses. To investigate the basis for the UVB‐induced barrier alteration, we assessed the epidermal lamellar body secretory system at various time points before and after barrier disruption with a single high dose of UVB (7.5 MED) to murine epidermis. Morphological data were correlated with changes in epidermal proliferation and lipid synthesis, indicative of lamellar body generation. Twenty‐four hours following UVB, the stratum corneum (SC) is normal, but a layer of abnormal, vacuolated, and lamellar body (LB)‐deficient cells is present, immediately beneath the stratum granulosum (SG)/SC interface. Immediately subjacent to this band of damaged cells, normal keratinocytes that contain intact LBs are present. By 72 h, concomitant with the appearance of a barrier abnormality, extensively damaged cells persist at the SC/SG interface, and abnormal lamellar membrane structures appear in the lower SC. Upper stratum spinosum (SS) and lower SG cells appear normal, with increased numbers of LBs. A barrier abnormality is still present at 96 h, in association with membrane abnormalities in the lower SC interstices, but up to four normal‐appearing, subjacent SG cell layers are present. By 120 h, accelerated LB formation and precocious LB extrusion occur throughout the thickened SG; normal lamellar membranes are present in the lower SC; and barrier recovery is almost complete. Whereas, epidermal synthesis of the major barrier lipid species (i.e., cholesterol, fatty acids, and ceramides, including acylceramides) is reduced or unchanged at 24 and 48 h, it increases significantly 72 h after exposure to UVB. Therefore, the delayed disruption of the permeability barrier following acute UVB exposure results from the arrival of a band of lamellar body‐incompetent (i.e., damaged) cells at the SG/SC interface. The subsequent, rapid recovery of the barrier, in turn, results from compensatory hyperplasia of subjacent, undamaged SS/SG cells, generating increased numbers and contents of LB. These results underscore the critical role of the stratum compactum in mediating barrier function, and suggest that beneficial therapeutic effects of UV exposure may be due to enhanced lipid production and barrier regeneration.
Sunscreens used at the beach do not protect against erythema: A new definition of SPF is proposed
Authors: Wulf H.‐C. , Stender I.‐M. , Lock‐Andersen J.
Published: September 2011

Since sunscreens are recommended by doctors and used all over the world to protect against sun induced erythema, it is important to evaluate if sunscreens are used as recommended and if the intended effect is achieved. We refer to the findings of several studies performed on people at risk of sun‐burning at beaches in the vicinity of Copenhagen, Denmark. On a sunny day at the beach 65% of the sunbathers used one or more sunscreens. Of these, 46% used the sunscreen all over the body and a median sun protection factor (SPF) of 5–6 was used. The sunbathers used 0.5 mg/cm2 of sunscreen independent of skin type. Of the sunscreen users, 43%> applied the sunscreen after arriving at the beach and 43% reapplied the sunscreen after swimming. The sun exposure time and the sun exposure dose were almost identical among sunscreen users and non‐users. Self‐assessed redness of the skin demonstrated that more sunscreen users than non‐users reported to be red the day after sun exposure, 42 and 34%, respectively. Theoretical calculations support this finding and show a drastic reduction in the achieved photoprotection if a thinner layer than in the test situation is used. Sunscreens do not protect against erythema if not used as intended. Instead of changing people's habits, we suggest modifying the test method by adjusting the amount of sunscreen to that used in real life situations, 0.5 mg/cm2.
Travel to sunny countries is associated with changes in immunological parameters
Authors: Falkenbach A. , Sedlmeyer A.
Published: September 2011

Under laboratory conditions, various studies have shown that changes in immunological parameters must be expected after exposure to ultraviolet (UV) light. The objective of the present study was to evaluate, whether such changes can also be revealed after a vacation to a sunny country without prior adaptation to ultraviolet radiation. In 32 volunteers white blood cells, lymphocyte subpopulations, sIL2‐R, sCD14, immunoglobulins and complement factor C3 were determined before and after a vacation in a country with abundant sunshine during winter. The subjects received relevant doses of UVB as confirmed by questionnaires, UVB‐dosimetry and the significant increase of 25‐hydroxyvitamin D. After vacation, there was a significant decrease of the CD4/8 ratio and the serum concentration of IgG. The serum concentration of sIL2‐R, sCD14, IgA and C3 was increased after the journey. Sunshine exposure without prior adaptation may be responsible for significant alterations in the immune system in association with a vacation during winter.
Porphyria cutanea tarda and hematologic malignancy ‐ a report of 4 cases
Authors: McKenna D. B. , Browne M. , O'Donnell R. , Murphy G. M.
Published: September 2011

Porphyria cutanea tarda has been reported in association with a variety of myeloproliferative and lymphoproliferative disorders, suggesting a possible association between these conditions. We describe four patients presenting within a 12 month period with sporadic porphyria cutanea tarda shortly following the diagnosis of hematologic malignancy. A review of the literature and evidence supportive of a causal association are presented.
In vitro spontaneous and UVB‐induced lymphocyte apoptosis are not specific to SLE
Authors: Abe M. , Ishikawa O. , Miyachi Y. , Kanai Y.
Published: September 2011

We studied in vitro spontaneous and ultraviolet light (UV)‐induced lymphocyte apoptosis in patients with systemic lupus erythematosus (SLE, n=11), cutaneous lupus erythematosus (CLE, n=8), and other collagen diseases (n=6), as well as normal individuals (n=6). Apoptosis was confirmed by the presence of a 180 bp DNA ladder on gel electrophoresis. UVB‐induced apoptosis was observed in 4 of 11 patients with SLE (36.3%), 3 of 8 patients with CLE (37.5%) and 2 of 6 patients (33.3%) with other collagen diseases. There was no clinical correlation between clinical photosensitivity and UV‐induced apoptosis. Similarly, spontaneous apoptosis was also found in lymphocytes from patients with diseases other than SLE. No apoptosis was found in normal subjects with or without UVB irradiation (25 mJ/cm2). These data suggest that UV‐induced lymphocyte apoptosis may not be specific to SLE but may be common in collagen diseases.
Relationship between skin phototype and MED in Korean, brown skin
Authors: Youn J. I. , Oh J. K. , Kim B. K. , Suh D. H. , Chung J. H. , Oh S. J. , Kim J. J. , Kang S. H.
Published: September 2011

The Fitzpatrick skin classification has been a useful method to categorize cutaneous sensitivity to ultraviolet radiation (UVR), although it was based originally on responses in white skin. Because the relevance of this phototype in brown skin is in question, we investigated skin phototypes of university students by a self‐reporting questionnaire and measured their MEDs in Korean, brown skin. After studying our explanation of the definition of Fitzpatrick skin types, 707 Korean university students answered the questionnaire. We then measured UVB MEDs in 156 randomly selected male students. The order of frequency of skin type was type III (55.0%), IV (29.0%), and V (12.3%) by the questionnaire, with the sun sensitive categories (types I and II) reported only for 3.7%. There was no significant difference in MEDs between types IV and V, and the mean MED of each skin type did not show a monotonic increase with increasing skin type. Subjects with MEDs of 70–90 mJ/cm2 (corresponding to the MED of skin type V, as proposed by Pathak & Fitzpatrick) represented about half or more of the subjects in all categories, even types II and III. Subjects with MEDs lower than 60 mJ/cm2 were more prevalent in types II and III compared with types IV and V We suggest that there is at best a weak relationship between the skin types, by the Fitzpatrick method, and MEDs in Korean, brown skin.