Phototherapy-induced blistering reaction and eruptive melanocytic nevi in a child with transient neonatal porphyrinemia.

Neonatal blue-light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity-induced epidermal injury, that of porphyrins and the influence of neonatal blue-light therapy, in this unique phenomenon are discussed.

Transient Porphyrinemia in a Neonate: A Case Report.

We describe a neonate with anemia, thrombocytopenia, and hyperbilirubinemia secondary to hemolytic disease of the newborn. After phototherapy for hyperbilirubinemia, the neonate developed a photodistributed eruption with high serum and urine porphyrin levels. This transient porphyrinemia resolved at 1 month.

Liver failure after Hydroxycut™ use in a patient with undiagnosed hereditary coproporphyria.

We report the case of a young male presenting with cholestatic liver failure. After an extensive workup, the etiology of the liver failure was determined to be due to hereditary coprophorphyria (HCP). The inciting event was the use of Hydroxycut™, an over-the-counter supplement to promote weight loss that has been reported to cause oxidative liver injury in vulnerable populations. Although HCP is a rare cause of cholestatic liver failure, it is treatable if diagnosed correctly and in a timely manner. In this clinical vignette, we discuss a case that highlights the genetic susceptibility to disease that can be unmasked by environmental exposures. We also review the relevant literature on Hydroxycut™ and how it can affect hepatic function.

Phototherapy induced cutaneous eruption in a neonate with transient porphyrinemia.

UNLABELLED: Phototherapy for hyperbilirubinemia has rare complications. We report a case of phototherapy induced eruption in a neonate with transient porphyrinemia. Our patient received phototherapy due to hyperbilirubinemia secondary to erythroblastosis fetalis (hemolytic disease of the newborn). He developed a cutaneous rash in the light-exposed areas of his skin. Erythrocyte and plasma porphyrins were elevated at the time. Phototherapy induced eruption with a transient porphyrinemia is rare. Upon review of the literature, we found only 5 other cases of patients with phototherapy induced rash and elevated porphyrins reported. We compared the five other reported cases to our case, looking at drug exposure, age, and receipt of exchange transfusion. CONCLUSION: While this is an uncommon occurrence, transient porphyrinemia should be considered in neonates with phototherapy induced cutaneous eruption and erythroblastosis fetalis.

Pseudoporphyria following self-medication with chlorophyll.

Two cases of pseudoporphyria are described in which the clinical features of porphyria cutanea tarda occurred in the absence of abnormalities in porphyrin metabolism. Both patients presented with skin fragility and bullae on the dorsal aspect of the hands. The patients consumed a commercial liquid chlorophyll drink in which we detected fluorescent compounds with characteristics typical of previously described chlorophyll derived photosensitisers.

Effects of high-intensity training and resumed training on macroelement and microelement of elite basketball athletes.

The purpose of this study was to assess the effects of high-intensity training and resumed training in hot and humid environment on plasma macro- and microelements levels of elite Han Chinese basketball players. Ten well-trained elite basketball athletes' plasma macroelements (chlorin, sodium, potassium, and calcium), creatine kinase (CK), and creatine kinase-MB (CK-MB) were measured before and after a 2-h high-intensity training, and microelements (zinc, copper, iron, and selenium) were determined before and after a 1-week high-intensity training and after a 1-week resumed training. The blood CK and CK-MB levels of the elite basketball athletes were significantly increased (P < 0.05) after high-intensity basketball training. The macroelements (chlorin, sodium, and calcium) levels of blood increased significantly except potassium after high-intensity basketball training. No significant differences (P > 0.05) were found in zinc and copper levels; nevertheless, the levels of plasma selenium and plasma iron were significantly lower (P < 0.05) after a 1-week high-intensity training. After a 1-week resumed training, except zinc, all of microelements measured had a trend toward original levels. These results implicated that high-intensity training would provoke the change of macroelements which would lead to electrolyte disturbance. In addition, the present study suggested that a 1-week high-intensity training would have an impact on microelement levels, especially for selenium and iron.

Pharmacokinetic study of a novel sonosensitizer chlorin-e6 and its sonodynamic anti-cancer activity in hepatoma-22 tumor-bearing mice.

PURPOSE: The sonodynamically induced anti-tumor effect of chlorin-e6 (Ce6) was studied in mice bearing hepatoma-22 solid tumors. METHODS: In order to determine the optimum timing of ultrasound exposure after administration of Ce6, the Ce6 concentrations in plasma, skin, muscle and tumor were estimated by measuring the fluorescence intensity of tissue extractions with a fluorescence photometer based on the standard curve. A three-dimensional optical imaging system (IVIS spectrum) was used further to characterize the distribution of Ce6 in H-22 tumor. The anti-tumor effects were estimated by measuring tumor size after sonodynamic therapy. RESULTS: Similar pharmacokinetic trends of Ce6 in mice were observed either by fluorescence spectrophotometry or by bio-optical imaging. The results also demonstrated that Ce6 has a preferential localization in tumors, but low accumulation and rapid clearance in normal tissues. The results of anti-tumor effects revealed that at an ultrasound intensity of 4 W/cm(2) and a Ce6 dose of ≥10 mg/kg, a significant synergistic effect of ultrasound combined with Ce6 was observed, reducing the tumor volume significantly. CONCLUSION: Chlorin-e6 is a potential sonosensitizer for fluorescence imaging as well as for sonodynamic therapy for cancer. The anti-tumor effect of ultrasound could be enhanced in the presence of Ce6, which might be involved in a sonochemical mechanism.

Erythropoietic protoporphyria in Sweden: demographic, clinical, biochemical and genetic characteristics.

OBJECTIVE: To investigate the demographic, clinical, biochemical and genotypic features of patients with erythropoietic protoporphyria (EPP) in a Swedish cohort. DESIGN: Cross-sectional questionnaire, biochemical and genetic study. SETTING: Sweden. SUBJECTS: Fifty-one Swedish individuals known in 2008 to have EPP confirmed by molecular diagnosis. There were no exclusion criteria; all patients were included in the demographic and genetic study. A total of 92% participants completed the questionnaire study and 82% the biochemical study. RESULTS: The prevalence of EPP was 1 : 180,000. Nine novel ferrochelatase gene mutations were found. The most commonly reported age at onset of symptoms was the first year of life and the mean age at diagnosis was 22 years. Painful photosensitivity was the main symptom. Exogenous factors other than sunlight were frequently reported to cause cutaneous symptoms. One in five patients reported a positive effect of beta-carotene therapy. A marked impact of EPP on quality of life was reported. Women had a significantly lower mean erythrocyte protoporphyrin concentration than men. Of all participants, 84% had insufficient vitamin D concentrations, 44% had below normal serum ferritin or transferrin saturation levels and red cell abnormalities were common. CONCLUSIONS: The notably delayed diagnosis suggests the need for an increased awareness of EPP. Disturbed erythropoiesis, biochemical signs of iron deficiency and low vitamin D levels are frequent findings in this disease. New and better treatments are needed as current treatment options for symptom amelioration are limited. Vitamin D supplementation should be considered.

Erythrocyte protoporphyrin fluorescence as a potential marker of diabetes.

Protoporphyrin (PpIX), a porphyrin derivative, is the intermediate metabolic precursor of the heme molecule. Abnormal metabolism of total erythrocyte PpIX has been observed in diseases such as cancer, lead poisoning, psoriasis, iron deficiency anemia and acute porphyries. Diabetes mellitus (DM) is a complex metabolic syndrome in which hyperglycemia is the primary clinical manifestation and contributes to the diabetic complications. The aim of this study was to evaluate the utility of fluorescence spectroscopy of erythrocyte PpIX for monitoring the early stages of diabetes. A total of 14 male C 57BL mice, 6 weeks old, were divided into two groups: diabetic and non-diabetic. Diabetes was induced by intraperitoneal injection of streptozotocin (SZT). Blood cells were cultured with standard and 50 mM supplemented RPMI medium. Blood smears were prepared and stained for qualitative morphology analysis under optical microscopy. Blood porphyrin autofluorescence was analyzed by fluorescence spectroscopy. Characteristic PpIX emission spectra were obtained by exciting the samples at 405 nm. Average blood glucose was lower in the control group than in the diabetic group (156.50 +/- 8.11 mg/dL vs. 371.10 +/- 14.43 mg/dL, P < 0.05). Both diabetic and glucose-cultured erythroblasts showed a significant decrease (around 30.5% and 40%, respectively) in the emission band intensity at 635 nm. Our results indicate that the erythrocyte PpIX profile could be used as a biological monitor for diabetes.

Therapeutic effects of NaFeEDTA-fortified soy sauce in anaemic children in China.

The therapeutic effects of NaFeEDTA-fortified soy sauce on anaemic students were investigated. Three hundred and four iron-deficient anaemic school children (11-17 years) were randomly assigned to three treatment groups: control group (consuming non-fortified soy sauce), low-NaFeEDTA group (consuming fortified soy sauce, providing 5 mg Fe/day) and high-NaFeEDTA group (consuming fortified soy sauce, providing 20 mg Fe/day). Blood haemoglobin (Hb) levels were determined before and after 1 month, 2 months and 3 months of intervention. In addition, serum iron (SI), serum ferritin (SF), free erythrocytic porphyrin (FEP), total iron binding capability (TIBC) and transferritin (TF) were measured before and after consumption of soy sauce for 3 months. The results obtained herein show that the parameters measured were not changed remarkably within the 3-month intervention in the control group (P < 0.05). However, increased Hb, SI, SF and TF levels and decreased TIBC and FEP levels were observed in both the high-NaFeEDTA group (P <0.01) and the low-NaFeEDTA group (P < 0.05). The effectiveness of iron intervention in the low-NaFeEDTA group and high-NaFeEDTA group had no statistical significance after 3 months. It was concluded that nutritional intervention for anaemic students using NaFeEDTA-fortified soy sauce could play a positive role in the improvement of iron status and control of anaemia.

Blisters on psoriatic lesions treated with TL-01 lamps.

BACKGROUND: Asymptomatic blisters on psoriatic plaques are an uncommon adverse effect of TL-01 (UVB narrow-band 312 nm) phototherapy. OBJECTIVE: We report 7 new cases aiming to clarify the pathogenesis. METHODS: Blisters were biopsied at different times after onset. Blood porphyrins and antibodies to nuclear antigens and the cell surface of keratinocytes were investigated. RESULTS: We observed 7 asymptomatic blistering eruptions strictly limited to recovering psoriatic plaques. Biopsies taken within 24 h showed junctional detachment and apoptotic necrosis of basal keratinocytes. After 48 and 72 h, the blisters were intraepithelial, due to basal cell regeneration, and were no longer evident at 96 and 120 h. Dermal inflammation was always mild. Direct immunofluorescence tests as well as stainings for p53 protein did not show substantial changes. Blood investigations were negative. CONCLUSIONS: TL-01 blisters are caused by the quick reduction of acanthosis and desquamation before defensive mechanisms, i.e. the increase in the thickness of the stratum corneum and pigmentation, develop. However, the pathogenetic mechanisms of apoptosis of keratinocytes remain unknown.

Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles.

The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumours. The aim of this work was to determine the kinetics of porphyrin generation in tissues after topical application of ALA delivered in different vehicles on the skin overlying the tumour and normal skin of mice. Maximal accumulation was found in tumour 3 h after ALA application in both cream and lotion preparations. Normal and overlying tumour skin tissues showed different kinetic patterns, reflecting histological changes when the latter is invaded by tumour cells. Liver, kidney, spleen and blood porphyrins also raised from basal levels, showing that ALA and/or ALA-induced porphyrins reach all tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faeces. ALA lotion applied on the skin overlying the tumour induced higher accumulation of tumoural porphyrins than cream, and lotion applied on normal skin appeared to be the most efficient upon inducing total body porphyrins. This work has demonstrated the great influence of the formulation of ALA vehicle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours.

Purpuric phototherapy-induced eruption in transfused neonates: relation to transient porphyrinemia.

OBJECTIVE: Blue light phototherapy is commonly administered to neonates as treatment of indirect hyperbilirubinemia, often in conjunction with blood transfusions to treat hemolytic anemia. We observed a distinctive cutaneous complication of phototherapy in six neonates with hyperbilirubinemia. METHODOLOGY: We studied the clinical and histologic characteristics of the eruption, as well as the porphyrin levels in affected neonates. Five of the patients had erythroblastosis fetalis; the other had profound anemia from twin-twin transfusion. All of the neonates developed purpuric patches at sites of maximal exposure to the phototherapy lights, with dramatic sparing at shielded sites within 24 hours after initiation of the phototherapy. On discontinuation of phototherapy, all eruptions cleared within 1 week. Examination of skin biopsy sections showed purpura without significant inflammation or keratinocyte necrosis. Plasma porphyrins (copro- and proto-) were elevated in the two patients in which they were assessed. CONCLUSIONS: The distribution of the eruption in areas exposed to light and presence of circulating porphyrins suggest that porphyrinemia may underlie the light-induced purpuric eruption. Additional studies will be required to determine definitively the mechanisms of both the purpuric phototherapy-induced eruption and the development of increased blood porphyrin levels in these transfused neonates.

Delivery of benzoporphyrin derivative, a photosensitizer, into atherosclerotic plaque of Watanabe heritable hyperlipidemic rabbits and balloon-injured New Zealand rabbits.

In this study we compared the plasma distribution and arterial accumulation of a photosensitizer, benzoporphyrin derivative (BPD), in two models of atherosclerosis: the spontaneous lesions of the Watanabe heritable hyperlipidemic (WHHL) rabbit and induced lesions of the balloon-injured, cholesterol-fed New Zealand white (NZW) rabbit. Selective uptake and retention of a photosensitizer by the abnormal portion of a vessel is a necessity in order for photodynamic therapy to become a successful modality for inhibition of intimal hyperplasia, selective removal of atherosclerotic tissue or imaging of diseased arteries. Liposome-based formulations were compared to freshly isolated native low density lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles for BPD. Plasma distribution of the photosensitizer was analyzed by KBr density gradient ultracentrifugation. Although the delivery vehicle influenced plasma distribution immediately postinjection, BPD subsequently partitioned according to the plasma concentration of the lipoproteins. Photosensitizer level in plaque and normal artery specimens was determined by ethyl acetate extraction and spectrofluorometric measurement. The measurement of BPD in normal and atherosclerotic arterial tissue demonstrated a selective accumulation in atherosclerotic tissue. Preassociation with LDL and Ac-LDL enhanced accumulation of BPD in atherosclerotic tissue when compared with normal artery (mean ratios of 2.8 and 4.1 were achieved, respectively). These results indicate that the preferential uptake of BPD by atherosclerotic plaque can be enhanced by preassociation with plasma lipoproteins, suggesting that light activation could lead to a highly selective destruction of diseased vascular tissue.

Inhibitory effect of selenium on enzymes involved in heme biosynthetic pathway in chick embryos.

Effect of different concentrations of selenium (Se) on heme biosynthesis was studied at different developmental stages of chick embryo. The first rate limiting enzyme ALA-synthase (ALA-S; E.C.2.3-1.37) activity was enhanced by selenium, while hepatic and blood ALA-dehydratase activity (ALA-d; E.C.3.2.1.24) was decreased. Hepatic and blood free-sulfhydryl (-SH) group contents were significantly decreased by Se. Further, hepatic aminolevulinic acid (ALA) and total blood porphyrin levels were enhanced and hepatic heme levels were depleted by selenium exposure. Heme biosynthesis was maximally inhibited in the E4 (4th day injected embryos) when compared to later periods.

Neonatal bullous eruption as a result of transient porphyrinemia in a premature infant with hemolytic disease of the newborn.

We describe the clinical and biochemical features of an infant with marked transient porphyrinemia in whom blistering developed while the infant was undergoing phototherapy for severe Rh isoimmunization. The cause of the transient porphyrinemia was likely to be multifactorial--abnormal porphyrin metabolism or accumulation in a premature infant with multisystem disease and multiple drug therapy. In addition, the infant received an unusually large amount of phototherapy. No evidence for an associated porphyria has been obtained. We believe this is a unique case because transient porphyrinemia associated with neonatal blistering does not appear to have been reported previously. Furthermore, blistering associated with phototherapy is rare.

[The mechanisms of the porphyrin conformation of normal blood hemoglobin and in pathology]. / Mekhanizmy konformatsii porfirinov gemoglobina krovi v norme i pri patologii.

The spectra of resonance Raman scattering of blood in norm and under pathology (myocardial infarction and sepsis), as well after artificial hemotransfusion or UV photomodification have been studied. It has been shown that under heart pathology the structure of hemoglobin porphyrin macrocycle of erythrocytes changes, the size of porphyrin "nucleus" increases. The opposite conditions are observed at blood sepsis. It has been found that the traditional methods in tissue restoration, hemotransfusion and UV photomodification of blood don't result in complete restoration of hemoporphyrin molecule.

Randomized, placebo-controlled trial of iron supplementation in infants with low hemoglobin levels fed iron-fortified formula.

In spite of the declining prevalence of iron-deficiency anemia, a large proportion of low-income infants have "low-normal" (11-11.5 g/dL) and "low" (less than 11 g/dL) hemoglobin (Hgb) values. Because most of these infants are fed iron-fortified formulas, it was of interest whether additional iron supplementation would enhance Hgb values. A cohort of 334 healthy, inner-city, minority, 6-month-old infants, fed iron-fortified formulas, with Hgb values ranging from 9 to 11.5 g/dL, participated in a double-blind, randomized, placebo-controlled trial of supplemental iron at 0, 3, and 6 mg/kg per day for 3 months. Hemoglobin values increased significantly with age, regardless of assignment to placebo or supplemental iron (means for the entire cohort: 6 months 10.9 g/dL, 8 months 11.2, 10 months 11.3, and 12 months 11.4). The proportion of "responders" (Hgb level increased greater than or equal to 1 g/dL) was 34% and did not differ significantly by placebo or iron dose. There were no significant differences in mean corpuscular volume or levels of erythrocyte porphyrins or serum ferritin between treatment groups. The implications of this clinical trial are twofold: (1) screening healthy infants fed iron-fortified formula at the age of 6 months is not justified, regardless of socioeconomic status; (2) the clinical practice of routinely treating low-income, "low-Hgb" infants with iron supplementation, without regard to dietary considerations, is unwarranted.

Screening with zinc protoporphyrin for iron deficiency in non-anemic female blood donors.

Iron-depleted donors are at increased risk of developing anemia; if these donors could be identified by a screening test, iron supplementation or decreased donation frequency could be considered. Tests to determine serum ferritin, blood hemoglobin, and erythrocyte (Erc)-zinc protoporphyrin concentrations were examined in 679 consecutive female blood donors to identify donors with non-anemic iron deficiency. The test to determine serum ferritin is expensive and slow, whereas the two latter tests are rapid and less costly and could therefore be used for screening. Women in the fertile age groups had the lowest average serum ferritin values. In all, 93 women (13.7%) had depleted iron stores, as indicated by serum ferritin concentrations less than 14 micrograms/L. In these women, a much better correlation was found between Erc-zinc protoporphyrin and serum ferritin (rs = -0.49, P less than 0.001) than between blood hemoglobin and serum ferritin (rs = 0.31, P less than 0.01). These findings suggest that measurement of Erc-zinc protoporphyrin is superior to that of blood hemoglobin in identifying donors with non-anemic iron deficiency.