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The porphyrias are rare disorders of haem biosynthesis. Diagnosis requires demonstrating increased porphyrins or porphyrin precursors in blood, urine and faeces. Patients may only be investigated once, and therefore, understanding the preanalytical factors affecting the reliability of results is crucial. Guidance for sample handling exists, but published evidence regarding the stability of porphyrins and their precursors is limited. The aim of this study was to evaluate the effect of light exposure and different storage temperatures on analyte stability for measurement of urinary aminolaevulinic acid and porphobilinogen, total urine porphyrin and plasma porphyrin. Our results confirm that all samples should be protected from light. Results from samples exposed to light for greater than 4 hours should be interpreted with caution and repeat samples requested. If transported to a specialist laboratory, samples should be stored at 4°C before transport. Transit time at ambient temperatures should be less than 24 hours., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The supramolecular complexation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) has been known to be highly specific in aqueous media. In this study, we have used NMR spectroscopy to reveal that this supramolecular system also works even in biologically crowded media such as serum, blood, and urine. A 13 C-labeled heptakis(2,3,6-tri-O-methyl- 13 C)-β-cyclodextrin ( 13 C-TMCD) was synthesized and studied using one-dimensional (1D) HMQC spectroscopy in serum and blood. The 1D HMQC spectrum of 13 C-TMCD showed clear signals due to the 2-, 3-, and 6-O 13 CH 3 groups, whose chemical shifts changed upon addition of TPPS due to quantitative formation of the 13 C-TMCD/TPPS=2/1 inclusion complex in such biological media. The 1 H NMR signals of non-isotope-labeled TPPS included by 13 C-TMCD were detected using the 13 C-filtered ROESY technique. A pharmacokinetic study of 13 C-TMCD and its complex with TPPS was carried out in mice using the 1D HMQC method. The results indicated that (1) 1D HMQC is an effective technique for monitoring the inclusion phenomena of 13 C-labeled cyclodextrin in biological media and (2) the intermolecular interaction between 13 C-TMCD and TPPS is highly selective even in contaminated media like blood, serum, and urine., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Porphyria cutanea tarda (PCT) is the most common porphyria worldwide. The known acquired precipitating factors that induce PCT include alcoholism, hepatitis C virus infection, human immunodeficiency virus infection, and estrogen intake. Hereditary hemochromatosis is considered an inherited risk factor. The aim of this study was to describe and analyze precipitating factors and family history, with emphasis on PCT management., Methods: A retrospective study of 87 patients with PCT was conducted between January 2002 and December 2017., Results: A male predominance of 1.8 : 1 was found. The median age at diagnosis was 49 years (range 18-71). Family history of PCT was observed in 19.5% of patients. Two or more acquired precipitating factors were present in 42.5%. Patients were treated with antimalarial monotherapy (72.4%), antimalarial combined with phlebotomy (22.9%), and only with phlebotomy (4.6%). Acquired precipitating factors and inherited factors were not associated with treatment group. There was a difference in 24 h-UP normalization rate between treatment groups; combined therapy takes longer than antimalarial monotherapy, 38 months versus 15 months, respectively (CI 95%, 6.5-63.5 vs. 12.9-17) (log-rank test, P = 0.004)., Conclusion: Precipitating factors did not seem to be associated with treatment choice; however, all acquired and inherited precipitating factors should be investigated, and the choice between phlebotomy and/or antimalarials should be individualized. All dermatologists treating PCT patients should observe transferrin saturation and ferritin levels to search for underlying hereditary hemochromatosis., (© 2019 The International Society of Dermatology.)

Photodynamic therapy (PDT) is an approved modality for the treatment of various types of maligancies and diseased states. However, most of the available photosensitizers (PS) are highly hydrophobic, which limits their solubility and dispersion in biological fluids and can lead to self-quenching and sub-optimal therapeutic efficacy. In this study, chlorin e6 (Ce6)-coated superparamagnetic iron oxide nanoparticle (SPION) nanoclusters (Ce6-SCs) were prepared via an oil-in-water emulsion. The physical-chemical properties of the Ce6-SCs were systematically evaluated. Dual-mode imaging and PDT was subsequently performed in tumor-bearing mice. Chlorin e6 is capable of solubilizing hydrophobic SPION into stable, water-soluble nanoclusters without the use of any additional amphiphiles or carriers. The method is reproducible and the Ce6-SCs are highly stable under physiological conditions. The Ce6-SCs have an average diameter of 92 nm and low polydispersity (average PDI < 0.2). Encapsulation efficiency of both Ce6 and SPION is ≈100%, and the total Ce6 payload can be as high as 56% of the total weight (Ce6 + Fe). The Ce6-SCs localize within tumors via enhanced permeability and retention and are detectable by magnetic resonance (MR) and optical imaging. With PDT, Ce6-SCs demonstrate high singlet oxygen generation and produce a significant delay in tumor growth in mice.

Benzene is an environmental and occupational contaminant. Health hazards associated with occupational benzene exposure is a major public health problem in China. In this study, we analyzed metabolite profiles among plasma samples collected from benzene-exposed workers with low white blood cell count (BLWs) and healthy controls using high-performance liquid chromatography-time-of-flight mass spectrometry. To screen potential benzene hematotoxicity biomarkers and metabolic pathways, principal component analysis was used to examine metabolite profile changes in plasma samples. The alterations in fatty acid oxidation (FAO) pathway were consistent with our previous findings in a mouse model; hence, two key genes were selected and verified in WBC samples. A total of nine identified metabolites were significantly changed in BLWs, which were involved in glutathione metabolism, porphyrin metabolism, lipid metabolism pathway, and FAO metabolism. Furthermore, compared with healthy controls, the mRNA expressions of carnitine acyltransferase (CRAT) and ACADVL were significantly increased in BLWs. Particularly, WBC counts was negatively correlated with the expression of AVADVL in BLWs. These aberrant metabolites could act as potential biomarkers for benzene hematotoxicity. In addition, fatty acid oxidation pathway may play a critical role in the development of hematotoxicity caused by benzene.

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., (© 2018 Wiley Periodicals, Inc.)

In this study, we compared different types of biomolecular markers in kidney cancer patients and in normal healthy controls, using fluorescence emission spectra and synchronous fluorescence excitation spectra. We were able to provide an accurate classification of the spectral features of kidney cancer patients relative to that of normal controls, in terms of the concentration ratios of biomolecules (viz., tryptophan, NADH, FAD, basic porphyrin, and acidic porphyrin) based on the intensity of their spectral peaks. The specificity and sensitivity of the method were 90%. The rationale of our current approach is to evolve an innovative protocol for the spectral characterization of in vitro optical analyses suitable for both small clinics and hospitals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Congenital erythropoietic porphyria is a rare autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase, owing to mutations in UROS in chromosome 10. Occasionally, patients show a mild, late-onset disease, without germline UROS mutations, associated with haematological malignancies. We report a 65-year-old patient with photosensitivity, overexcretion of porphyrins and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possibly due to an inversion including 3q21 and 3q26 break points. After allogeneic stem-cell transplantation, complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations., (© 2017 British Association of Dermatologists.)

The porphyrias are disorders of haem biosynthesis which present with acute neurovisceral attacks or disorders of sun-exposed skin. Acute attacks occur mainly in adults and comprise severe abdominal pain, nausea, vomiting, autonomic disturbance, central nervous system involvement and peripheral motor neuropathy. Cutaneous porphyrias can be acute or chronic presenting at various ages. Timely diagnosis depends on clinical suspicion leading to referral of appropriate samples for screening by reliable biochemical methods. All samples should be protected from light. Investigation for an acute attack: • Porphobilinogen (PBG) quantitation in a random urine sample collected during symptoms. Urine concentration must be assessed by measuring creatinine, and a repeat requested if urine creatinine <2 mmol/L. • Urgent porphobilinogen testing should be available within 24 h of sample receipt at the local laboratory. Urine porphyrin excretion (TUP) should subsequently be measured on this urine. • Urine porphobilinogen should be measured using a validated quantitative ion-exchange resin-based method or LC-MS. • Increased urine porphobilinogen excretion requires confirmatory testing and clinical advice from the National Acute Porphyria Service. • Identification of individual acute porphyrias requires analysis of urine, plasma and faecal porphyrins. Investigation for cutaneous porphyria: • An EDTA blood sample for plasma porphyrin fluorescence emission spectroscopy and random urine sample for TUP. • Whole blood for porphyrin analysis is essential to identify protoporphyria. • Faeces need only be collected, if first-line tests are positive or if clinical symptoms persist. Investigation for latent porphyria or family history: • Contact a specialist porphyria laboratory for advice. Clinical, family details are usually required.

Aim: To evaluate clinical features and metabolic disorders in men and women with non-alcoholic fatty liver disease (NAFLD).

We studied the effects of medium pH on steady-state distribution of chlorine e6 and its derivatives between the main transport proteins of human blood plasma. The decrease in medium pH from weakly alkaline (pH 7.4) to acid (pH 5.0) was followed by an increase in relative affinity of chlorines to lipoproteins and reduced their affinity to serum albumin. pH-Dependent changes in the parameters of distribution of photosensitizers between the plasma and blood cells was revealed. We discussed the role of charge and polarity degree of photosensitizer molecule in the mechanism of binding to serum albumin. A possible role of changes in hydrogen ion activity in the processes of selective accumulation of chlorines by tumor cells is discussed.

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.

Congenital erythropoietic porphyria (CEP) is a rare genetic disease that is characterized by a severe cutaneous photosensitivity causing unrecoverable deformities, chronic hemolytic anemia requiring blood transfusion program, and by fatal systemic complications. A correct and early diagnosis is required to develop a management plan that is appropriate to the patient's needs. Recently only one case of X-linked CEP had been reported, describing the trans-acting GATA1-R216W mutation. Here, we have characterized two novel X-linked CEP patients, both with misleading hematological phenotypes that include dyserythropoietic anemia, thrombocytopenia, and hereditary persistence of fetal hemoglobin. We compare the previously reported case to ours and propose a diagnostic paradigm for this variant of CEP. Finally, a correlation between phenotype variability and the presence of modifier mutations in loci related to disease-causing gene is described., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2014 The Australasian College of Dermatologists.)

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.

The purpose of this study is to establish a sensing system to estimate relative talaporfin sodium concentration in skin to evaluate the risk of skin photosensitivity after photodynamic therapy (PDT) using percutaneous fluorescence spectroscopy. A prototype fluorescence sensing probe was made using a pair of 5-cm-long diffuse tips of plastic optical fibers for excitation light irradiation and fluorescence collection. Talaporfin sodium (2.5mg/kg) was intravenously administrated to three pigs, and the talaporfin sodium concentration in plasma was measured. The fluorescence sensing probe was attached to the skin and excited by a LED light with a peak wavelength of 409 ± 16 nm to obtain the mean area of the talaporfin sodium fluorescence spectral peak (Sfluo). The time history of the talaporfin sodium concentration in tissue was estimated using a two-compartment pharmacokinetic model. The time history of Sfluo was described as a composite function of the time history of the measured talaporfin sodium concentration in plasma and that of the estimated concentration in tissue as a double exponential decay function. The relative talaporfin sodium concentration in tissue and the relative contributions of fluorescence from tissue and plasma to Sfluo were estimated by the fluorescence system with the numerical pharmacokinetic model. Results also show that tissue compression equivalent to venous pressure might be effective to suppress the contribution of talaporfin sodium fluorescence in plasma., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Malaria is the most common disease transmitted by the bite by an infected female anopheles mosquito and caused by the plasmodium parasite. It is mostly prevalent in subtropical regions receiving abundant rain and supporting copious mosquito breeding. This disease is generally detected by the microscopic examination of blood films or antigen based rapid diagnostic test. Only occasionally the parasite DNA is detected using polymerase chain reaction in certain advanced, expensive laboratories., Methods: An innovative spectral detection method based on the fluorescence spectra of a set of blood plasma biomolecules [tyrosine, tryptophan, nicotinamide adenine dinucleotide (NAD), and flavin adenine dinucleotide (FAD)] and red blood cell (RBC)-associated porphyrin is being evolved by our group., Results: The research so far has exhibited sensitivity and specificity values exceeding 90% based on the spectral features of blood components of 14 malaria patients and 20 numbers of age adjusted normal controls. The fluorescent biomolecules go out of proportion when the malarial parasite breaks down the hemoglobin of blood., Conclusion: This technique has the potential to be used as an alternative diagnostic procedure for malaria since the instrumentation involved is portable and inexpensive., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000&#95;2014&#95;182.

Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nanoconstruct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart 'all-in-one' nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumour detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumours. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumours for photothermal therapy (PTT), and light to singlet oxygen for photodynamic therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs or therapeutic radio-metals into tumours.

Background & Aims: HCV is a major cause of chronic liver disease in Egypt. The aim was to study the prevalence of photosensitivity among asymptomatic HCV-infected patients and its possible relation to porphyrins levels and whether it can be considered an alarm for early diagnosis of the disease, which is the most important goal in the management., Methods: This study included 100 accidentally discovered HCV positive cases and 100 HCV negative healthy controls. All patients and controls were subjected to: Detailed history and clinical examination, dermatological examination including evaluation of reaction to solar exposure, measurement of serum AST, ALT, albumin, bilirubin, serum and urinary porphyrins levels., Results: The prevalence of photosensitivity among HCV-positive cases (33%) was significantly higher compared to 10% in the control group. Serum porphyrins were positive in 46 cases (46%), twenty-three cases (23%) had positive urinary porphyrins, while only four controls (4%) showed positive serum porphyrins and one (1%) showed positive urinary porphyrins, the difference was statistically significant. Cases with photosensitivity showed significantly higher prevalence of serum and urinary porphyrins existence as well as serum porphyrins levels. Levels of viraemia showed statistically significant relation to levels of porphyrins., Conclusion: Asymptomatic chronic HCV infection cases showed significantly high prevalence of photosensitivity, which is related to the associated disturbance of porphyrins metabolism. Photosensitivity can thus be considered an early marker of HCV infection. Patients discovered to have recently acquired photosensitivity should be screened for HCV infection especially in endemic areas like Egypt., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Serum ferritin is routinely used as a first line test for iron status. Testing subjects with low pre-test probability often results in unexpected abnormal results. Raised ferritin is typically found in subjects with iron overload, liver disease, malignancy or inflammation. We sought to determine whether primary care patients with high ferritin had either porphyria cutanea tarda (PCT) or hereditary haemochromatosis (HH)., Methods: Redundant serum samples were collected from consecutive specimens with high ferritin (>500 µg/L) which had been received from primary care sources. Samples were analysed for serum iron and iron-binding capacity and for porphyrins by fluorescence scanning and HPLC., Results: There were 240 samples (91 females, 149 males) which represented 2.7% of total over the collection period. Serum iron was 17.3 (18.9) µmol/L (median (IQR)), TIBC 47.3 (14.2) µmol/L and transferrin saturation 35.7 (41.1) %. There were 87/240 (36%) with transferrin saturation >45% (57 males, 30 females). Of the samples 19/236 (8%) were positive for porphyrins by spectrofluorimetry and 14/15 (4 insufficient sample) had total porphyrins >11.2 nmol/L (40(63) median (IQR)) with 3/15 (1.25%) having a typical pattern for PCT., Discussion: This study demonstrates the feasibility of cascading tests using laboratory protocols and confirms the ability to identify potential cases. However, further studies for HH genotype and urine and stool porphyrin analysis will be necessary to confirm the diagnoses., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Fluorescence spectral techniques are very sensitive, and hence they are gaining importance in cancer detection. The biomarkers indicative of cancer could be identified and quantified by spectral or time domain fluorescence spectroscopy. The results of an investigation of time-resolved spectra of cellular components of blood obtained from cervical cancer patients and normal controls are given. The cancer indicative biomarker in this paper is porphyrin; it has a fluorescence decay time of 60% more in samples of cancer patients than those of normal controls. Based on such measurements, a randomized set comprising samples from cancer patients and controls (N=27 in total) could be classified with sensitivity (92%) and specificity (86%).

Sickle cell disease (SCD) and thalassemia (Thal) are the most common inherited, autosomal, recessive blood disorders which lead to complications such as vasoocclusion and splenomegaly. Patients who suffer from these diseases have poor quality of life and shorter life span. The most common techniques for detection of these diseases are complete blood cell count, followed by electrophoresis and high performance liquid chromatography. In this connection, the results of this paper indicate the potential of a new technique, based on spectral analysis of blood plasma and cellular components, to detect SCD and Thal with accuracy of 90% and above. To the best of our knowledge this would be the first report on spectral pathology of hemoglobinopathy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in massive porphyrin accumulation in blood cells, which is responsible for hemolytic anemia and skin photosensitivity. Among the missense mutations actually described up to now in CEP patients, the C73R and the P248Q mutations lead to a profound UROS deficiency and are usually associated with a severe clinical phenotype. We previously demonstrated that the UROS(C73R) mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. We show evidence that the reduced kinetic stability of the UROS(P248Q) mutant is also responsible for increased protein turnover in human erythroid cells. Through the analysis of EGFP-tagged versions of UROS enzyme, we demonstrate that both UROS(C73R) and UROS(P248Q) are equally destabilized in mammalian cells and targeted to the proteasomal pathway for degradation. We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. Finally, in CEP mice (Uros(P248Q/P248Q)) treated with bortezomib (Velcade), a clinically approved proteasome inhibitor, we observed reduced porphyrin accumulation in circulating RBCs and urine, as well as reversion of skin photosensitivity on bortezomib treatment. These results of medical importance pave the way for pharmacologic treatment of CEP disease by preventing certain enzymatically active UROS mutants from early degradation by using proteasome inhibitors or chemical chaperones.

A novel optical platform based on DNA aptamer-functionalized SWCNTs (a-SWCNTs) is developed for multiplexed detection of plasma porphyrins. We have investigated the interactions of a-SWCNTs with heme (FePP), protoporphyrin (PP), coproporphyrin (CP), and uroporphyrin (UP). Two interaction mechanisms, specific binding, and nonspecific adsorption between porphyrins and a-SWCNTs are proposed based on observed optical signal modulations. The optical transduction signals are used to formulate a multiplexed detection strategy for the four porphyrin species without a laborious separation process. The detection scheme is sensitive, selective, and can readily be used for porphyrin detection in plasma samples when combined with a solvent extraction method. Our optical platform offers novel analytical tools for probing the surface chemistry at the porphyrin/a-SWCNTs interface, showing great promise for both research and clinical applications.

The porphyrias are a group of inherited disorders that result in defects in the enzymes of the haem biosynthetic pathway, causing photosensitive bullous skin eruptions or abdominal and neurological attacks. Enzymatic defects result in specific porphyrin excretory patterns that are diagnosed biochemically and can be confirmed by genetic testing. Defects in the coproporphyrinogen oxidase (CPOX) enzyme result in the autosomal dominant hereditary coproporphyria. Multiple mutations have been identified in the CPOX gene and incomplete penetrance is noted. Latent carriers without clinical evidence of disease are at risk of life-threatening attacks. Porphyria cutanea tarda may be inherited, but is more commonly acquired. Occasionally two forms of porphyria may co-exist. The importance of genetic testing is discussed., (© 2012 The Authors; Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.)

AIP is an acute liver disorder caused by a deficiency of porphobilinogen deaminase (PBGD) characterized by neuroabdominal symptoms. It is an autosomal dominant disease. However, homozygous dominant AIP (HD-AIP) have been described. In some cases erythrodontia was observed. CEP is an autosomal recessive disease produced by mutations in the uroporphyrinogen III synthase gene (UROS), characterized by severe cutaneous lesions and erythrodontia. The aim of the work was to establish the differential diagnosis of porphyria in a patient with abdominal pain, neurological attacks, skin symptoms and erythrodontia. The PBGD activity was reduced 50% and the genetic analysis indicated the presence of two genetic variants in the PBGD gene, p.G111R and p.E258G, a new genetic variant, revealing a case of heteroallelic HD-AIP. The patient, first diagnosed as a carrier of a dual porphyria: AIP / CEP based on the excretion profile of porphyrins, precursors and her clinical symptoms, would be an atypical case of human HD-AIP. These results would also suggest the presence of a phenocopy of the CEP, induced by an endogenous or exogenous factor. Our findings highlight the importance of genetic studies for a proper diagnosis of porphyria, prevention of its manifestation and its treatment.

Background & Aims: Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies., Methods: We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine., Results: The time to remission was a median 6.9 months for patients who received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a difference that was not significant (log-rank, P = .06 and P = .95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95-5.06) for all patients. Patients who received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment., Conclusions: Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. ClinicalTrials.gov number, NCT01573754., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne-linked conjugated porphyrin dimer (Oxdime) designed to have high near-infrared (NIR) 2-photon absorption cross-section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16-F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organs ex vivo at different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5-10 times higher than in other tissues. The fluorescence signal peaked at 3-12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment., (© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.)

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.

Comparative study has been carried of effect of the three-day long starvation, running, and their combination on morphological parameters of rat blood, lipid metabolism, and activity of blood Na,K-ATPase. Different effect has been shown of these stress factors on the blood erythrocyte composition. Starvation is accompanied by the most pronounced release of stored erythrocyte into blood, which results in a significant decrease both of the total amount of reticulocytes and the complete absence of reticulocytes of the I stage of maturity (the youngest). The running on treadmill led to a significant increase of the total amount of blood reticulocytes and to multiple increase of immature reticulocytes (RC-I and RC-II), which can indicate some stress of the bone marrow erythroid stem line. The curve of acid resistance of blood reticulocytes has shown the animal to experience the greatest stress at a combination of starvation and running. Starvation and running produced different effects on blood lipid characteristics. The content of triacylglycerides (TAG) in blood rose by 40% at starvation and decreased by 30% at running, a similar tendency being found for index of atherogeneity. The fatty acid composition of blood phospholipids at running and its combination with starvation practically did not differ from control. A change of Na,K-ATPase, which is so characteristic of reaction to various kinds of stress, sharply fell at starvation (by 22%), but increased at running (by 13%) and decreased markedly at combination of these actions. Absorption spectra of lipid extracts of the whole blood of the rats submitted to various stress actions showed that extracted from blood (at different amount depending on the kind of action) is an organic substance with coupled bonds, which absorbs light in the diapason of 360-620 nm. The absorption of light in the diapason of 400-410 nm has been found to belong to the Soret band of ferroheme and ferriheme. The shift of the Soret band indicates electron transitions in the iron cation. By the change and disappearance of the Soret band, it is possible to judge about the processes occurring in the lipid extract. The disappearance of the Soret band in the lipid extract indicates formation in it of steady radicals as a result of the ferriheme disintegration due to accumulation of energy in porphyrin, which does not seem to occur in the blood cell membranes. The iron atom in the ferriheme molecule is known to accept electron and yields a part of energy probably to porphyrin. Then ferriheme yields electron and becomes ferriheme with excess of energy in porphyrin. Hence, at admission of the next electron to the iron atom the porphyrin molecule is to get rid of the energy obtained earlier to prevent its disintegration. The heme is possible to be an accumulator and distributor of energy in tissue.

Photodynamic therapy (PDT) has recently been proposed as a possible indication in the conservative treatment of hereditary retinoblastoma. In order to create photosensitizers with enhanced targeting ability toward retinoblastoma cells, meso-tetraphenylporphyrins bearing one glycodendrimeric moiety have been synthesized. The binding properties to plasma proteins and photodynamic activity of two monodendrimeric porphyrins bearing three mannose units via monoethylene glycol (1) or diethylene glycol (2) linkers have been compared to that of the non-dendrimeric tri-substituted derivative [TPP(p-Deg-O-α-ManOH)(3)]. The dendrimeric structure was found to highly increase the binding affinity to plasma proteins and to modify to some extent plasma distribution. HDL and to a lesser extent LDL have been shown to be the main carriers of dendrimeric and non-dendrimeric compounds. The phototoxicity observed for the two glycodendrimers (1) and (2) (LD(50)=0.5 μM) in Y79 cells is of the same order of magnitude that for TPP(p-Deg-O-α-ManOH)(3) (LD(50)=0.7 μM), with a similar cellular uptake level for (1) and a lower for (2). A serum content increase from 2% to 20% (v/v) in the incubation medium was found to inhibit both cellular uptake and photoactivity of dendrimeric derivatives, whereas those of TPP(p-Deg-O-α-ManOH)(3) remained little affected. Specificities of glycodendrimeric porphyrins, combining a lower cellular uptake together with a higher affinity toward plasma proteins, make these derivatives possible candidates for a vascular targeting PDT., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Erythropoietic protoporphyria is a rare photodermatosis of childhood, and the diagnosis can be delayed. A deficient ferrochelatase enzyme leads to accumulation of protoporphyrins in the dermis, causing phototoxic burning., Objective: To report three cases with great variability in severity of symptoms and age at diagnosis. We discuss clinical and biochemical findings, mutation analysis, and therapeutic options., Methods: We report three cases with different degrees of photosensitivity, laboratory results, psychosocial impact, and preventive and therapeutic treatments., Results: The diagnosis of erythropoietic protoporphyria was confirmed by both typical elevation of plasma porphyrins and the discovery of a mutated FECH gene., Conclusion: Erythropoietic protoporphyria should be suspected in any cases of childhood photosensitivity. Systemic complications are unusual. Mutation analysis confirms the diagnosis. Photoprotection is the cornerstone of treatment.

We present an interesting case of porphria cutanea tarda with hereditary haemochromatosis and non-classical congenital adrenal hyperplasia in a postmenopausal woman. This unusual combination of conditions does not appear to be reported in the literature. The exact mechanism causing porphyria in this patient is not clear. We consider the possibility that in addition to iron accumulation and excess alcohol, altered steroid milieu may have been a possible trigger for the development of bullous lesions in this patient.

A review of the literature about the toxic effects of cadmium on the human body. We describe a patient with clinical and biochemical signs of an attack of acute porphyria imitated or severe lead poisoning. In the patient's blood was revealed a 3-fold, compared to the allowable rate, increase of cadmium in the normal lead content. We discuss the etiologic role of cadmium and the possible pathogenetic mechanisms of this pathological condition.

Erythropoietic, i.e., myelogenous porphyrias include erythropoietic protoporphyria and the very rare congenital protoporphyria and X-linked protoporphyria. Of these, in Finland only erythropoietic protoporphyria has been diagnosed, in which pain and swelling in the skin upon sunlight exposure are the most typical symptoms. A high protoporphyrin level in erythrocytes and a typical peak in the plasma porphyrin spectrum lead to diagnosis.

This study aims to prepare (99m)Technetium Pheophorbide-a ((99m)Tc-PH-A) complex and evaluate its efficiency as an infection imaging agent. First, PH-A was obtained from Spirulina maxima algae, and the product compound was confirmed using (1)H NMR and MS (ESI) methods. The PH-A was then labeled with (99m)Tc using the tin chloride method and its biological efficacy as a potential radiotracer for Staphylococcus aureus (S. aureus) infection was evaluated in bacterially infected and sterile inflamed rats. The radiochemical stability of the (99m)Tc-PH-A in human serum was determined by thin-layer radiochromatography (TLRC). The radiochemical purity was 87±3.2% and remained constant at more than 80±0.1% even in serum for 120 min after radiolabeling. These experiments indicated that the ratio of (99m)Tc-PH-A uptake in bacterially infected muscle, as compared to normal muscle, [target/non-target (T/NT)=5.6 at 1h] was over four times higher than that in sterile inflamed muscle (T/NT=1.29 at 1h). Disappearance of activity from the kidney and liver indicated that the urinary and hepatobiliary systems were the normal routes of excretion of the complex. (99m)Technetium Pheophorbide prepared with high yield is able to localize well in the bacterially infected muscle of the rats and (99m)Tc-PH-A may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 John Wiley & Sons, Ltd.)

The role of endogenous porphyrins in the effects of laser radiation of the red region (632.8 nm) on free radical processes in the blood of rats under endotoxic shock induced by the administration of lipopolysaccharide B (25 mg/kg) has been studied. The measurements of the functional activity of polymorphonuclear leukocytes (the method of luminol-dependent chemiluminescence), the superoxide dismutase activity of blood plasma (using nitro blue tetrazolium), and the degree of lipid oxidation of erythrocyte membranes (the method of fluorescence of cis-parinaric acid) have been carried out. It has been found that low-intensity laser radiation strongly affects all processes examined irrespective of the administration of lipopolysaccharide B. The effect of radiation was most pronounced in animals injected with the polysaccharide, the changes being dependent on the concentration of endogenous porphyrins in samples.

Purpose: Historically, cutaneous photosensitivity has been the most common side effect of treatment with light-activated drugs. Talaporfin sodium is a water soluble photosensitizer in commercial use and clinical development that is cleared from the body relatively rapidly. This trial was conducted to determine the period of skin photosensitivity in healthy subjects given talaporfin sodium and to determine the correlation between photosensitivity and plasma levels of talaporfin sodium., Methods: Twenty healthy volunteers were dosed with 0.25-1.0mg/kg talaporfin sodium and exposed at successive timepoints to a solar simulator applied to a small patch of skin on the back. Photosensitivity was assessed at these sites 24h later. Duration of photosensitivity and correlation with plasma drug concentration were analyzed., Results: Skin reactions were generally mild and were classified most commonly as asymptomatic erythema. Photosensitivity subsided in each subject between 1 and 3 weeks after dosing. Subjects no longer exhibited photosensitivity at plasma drug levels between 600 and 2900ng/ml in each subject. Two subjects in the lowest dose group did not exhibit photosensitivity despite plasma drug levels as high as 4000ng/ml., Conclusions: These results indicate that a clinically effective dose of talaporfin sodium was well-tolerated and that cutaneous photosensitivity was mild and resolved relatively rapidly., (© 2011 John Wiley & Sons A/S.)