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PubMed1999

Is monochromatic irradiation testing useful in the differentiation of drug-induced photosensitivity from chronic actinic dermatitis?

Chronic actinic dermatitis (CAD) is an uncommon, eczematous photosensitive eruption affecting predominantly elderly men and to which drug-induced photosensitivity may sometimes appear clinically identical. This retrospective study compares the monochromatic irradiation results in 11 patients with CAD and 14 patients with drug-induced photosensitivity, to assess whether such testing is useful in the differentiation of these two conditions. Thus, the action spectra of the drug photosensitivity patients were plotted and compared with those of 12 nonphotosensitive control patients: 10 patients were found to be photosensitive in the UVA range; the implicated drugs included quinine, sparfloxacin, amiodarone, doxycycline, mefenamic acid, nalidixic acid, fenbrufen, diclofenac, enalapril, diltiazem and prochlorperazine maleate. One patient on doxycycline was photosensitive in both the UVA and UVB ranges. The remaining three patients were not tested until after discontinuation of their drug and their light tests were then normal. In the CAD group, five patients were photosensitive in the UVA, UVB and visible light ranges and six were photosensitive in the UVA and UVB ranges. Comparison of the mean minimal erythema dose responses then demonstrated dissociation of the drug-induced from the CAD group in the UVB region; the result was statistically significant. This suggests that UVA-sensitivity dissociated from UVB-sensitivity is a relative indicator of drug-induced photosensitivity and monochromatic irradiation testing may therefore be helpful in the differentiation of these two disorders.

Adult↗
PubMed1998

Electroencephalographic photosensitivity among Zimbabwean youths.

To clarify the factors associated with electroencephalographic (EEG) photosensitivity, the records of patients who had EEG examinations in the city of Harare, Zimbabwe between 1968 and 1996 were studied. EEG photosensitivity was confirmed in 107 of a total of 9082 youths (aged 0-25 years), giving an overall photosensitivity prevalence of 1.17% in the study population. Photosensitivity occurred more frequently in females than in males, and the peak age period for its occurrence was during adolescence. A significantly higher prevalence of photosensitivity was recorded among Whites and Asians than among Blacks, while the Coloured population had an intermediate prevalence. The monthly and seasonal incidence of photosensitivity in the present study showed no correlation with the prevailing mean monthly or seasonal temperatures, sunshine duration and sunlight intensity in Harare during the period covered by the study. These findings indicate that sunshine-related factors do not play a dominant role in the occurrence of photosensitivity, thereby negating previous opinions which attributed the relative rarity of photosensitivity in black Africans to high levels of exposure to sunshine in tropical Africa. Our findings therefore corroborate the view that photosensitivity depends primarily on genetic rather than environmental factors.

Adolescent↗
PubMed2004

Clinical and epidemiologic characterization of photosensitivity in HIV-positive individuals.

BACKGROUND: An increased prevalence and severity of cutaneous photosensitivity has been recognized in association with human immunodeficiency virus (HIV) infection. However, this disorder remains poorly characterized in terms of its epidemiology, predisposing factors, clinical, and environmental associations. METHODS: To define the risk factors associated with the presence of photosensitivity among HIV-positive individuals, a cross-sectional study of 631 primary patient visits to an urban HIV Dermatology clinic between January 1997 and August 2001, inclusive, was conducted. A multivariate model was fit to estimate adjusted odds ratios for risk factors associated with photosensitivity diagnosis. Subsequently, a case-series of the patients with photosensitivity was reported. RESULTS: The overall prevalence of photosensitivity was 5.4%, while African-Americans (AA) exhibited a prevalence of 7.3%. In the multivariate model, using highly active anti-retroviral therapy (HAART) (OR=2.82, 95% CI: 1.13, 7.03) and being AA (OR=6.68, 95% CI: 1.56, 28.65) significantly increased the odds of photosensitivity. Patients with photosensitivity were more likely to present during periods of higher ultraviolet (UV) index (P=0.08). Two distinct clinical morphologies were noted: lichenoid and non-lichenoid, eczematous. Sub-morphologies in the non-lichenoid group were suggestive of differences in immunologic profile and estimated UV exposure. CONCLUSION: Photosensitivity associated with HIV infection is an increasingly recognized dermatologic condition with a heterogeneous clinical presentation. AA ethnicity and HAART were independent indicators for the diagnosis of photosensitivity, whereas CD4+ and UV exposure had non-significant associations. The subtleties in these and other clinical variables may directly aid in the recognition and diagnosis of this poorly characterized disorder.

Adult↗
PubMed1989

Analysis of cellular heterogeneity in the response of human leukemic cells to photosensitization induced by pyrene-containing fatty acid.

Incubation of cells with 12-(1-pyrene) dodecanoic acid (P12) followed by irradiation with ultraviolet light at 366 nm (UVA) resulted in cytotoxicity. We compared the photosensitivity to UVA irradiation of various human myelo-monocytic leukemic cell lines, their intra- and inter-clonal variability and correlated their photosensitivity to P12-uptake and metabolism. The fluorescence properties of pyrene were utilized for flow cytometric analysis of cell distribution with respect to P12-uptake as well as for sorting subpopulations differing in their fluorescence. Spectrofluorometric analysis of the total cell-associated fluorescence and of the cellular lipids-associated fluorescence were also carried out. Considerable heterogeneity in P12-uptake and photosensitivity was found not only among cell lines, but also in the response of different clones and among the individual cells in specific clonal populations. Within a clone, photosensitivity was related to the amount of P12 taken up by the individual cells, while among different cell lines and their clones the photosensitivity was correlated with the proportion of cellular pyrene-linked phospholipids. The larger the fraction of pyrene-linked phospholipids within the cell--the more sensitive it was to UVA-irradiation. Photosensitivity could be affected by changing the proportion of cellular pyrene-linked phospholipids. Cells treated with cAMP showed an increase in total P12-uptake, but the proportion of pyrene-linked phospholipids was reduced, resulting in lower photosensitivity. These findings, demonstrating that by manipulating lipid metabolism photosensitivity can be modified, may prove useful in a clinical setting for selective photosensitization of malignant cells.

Cell Survival↗
PubMed1997

Role of delivery vehicles for photosensitizers in the photodynamic therapy of tumours.

The use of photosensitizing drugs associated with different types of delivery vehicle has received strong interest within the field of the photodynamic therapy of tumours. Lipid-based delivery vehicles, such as liposomes and oil emulsions, allow the administration of water-insoluble photosensitizers, widening the choice of photosensitizers potentially useful for treating tumours. In some cases, these delivery vehicles increase the selectivity of tumour targeting by favouring photosensitizer uptake in tumour tissue. However, a higher selectivity of tumour targeting could be obtained through the association of photosensitizers with delivery vehicles which can interact preferentially or specifically with tumour cells. With this aim in mind, low-density lipoproteins (LDLs) and monoclonal antibodies, in particular, are regarded as the most promising delivery systems for anticancer drugs. Some pharmacokinetic studies with LDL-associated photosensitizers have demonstrated a higher tumour uptake compared with the same photosensitizers delivered with other formulations. Monoclonal antibody-coupled photosensitizers have been tested mainly in vitro, and have shown a high selectivity towards cells expressing specific antigens. Only a limited number of reports are available on the biodistribution of immunoconjugated photosensitizers and on their selectivity in vivo, so that their importance for the selectivity of tumour targeting has not yet been defined.

Antibodies, Monoclonal↗
PubMedDate not supplied

The prognosis of photosensitivity.

Since 1968, annual EEG recordings during photic stimulation using a standardised technique have been made on photosensitive patients and siblings. In 1983, 72 were aged greater than or equal to 20 years and 14 were aged 16-19 years. Mean duration of follow-up was 9.8 +/- 4.8 years. Seventy-five patients were treated with sodium valproate (VPA), which was withdrawn in 15 but restarted in eight because of return of photosensitivity. Eighty-two patients had seizures at some time; at follow-up 58 were receiving monotherapy with VPA, seven were receiving comedication, and three were taking other drugs. Fifty-four of them were seizure free, as were 10 of the 15 who were not being treated with drugs. Photosensitivity disappeared in 44 of 65 patients at a mean dosage of VPA at 21.5 +/- 6 mg/kg day. In 55 of 86 patients photosensitivity was no longer present at follow-up; in 18, slight abnormality was evoked by intermittent photic stimulation, and in 13, photoconvulsive responses were still present. Eighteen patients were not receiving drugs, 10 of them being no longer photosensitive at the mean age of 24.5 +/- 4.9 years. Thirty-one treated and untreated patients were still photosensitive at age 21.5 +/- 3.4 years. Photosensitivity disappeared earlier in those treated with VPA than in the untreated. Spontaneous remission in the treated cases may have occurred at 22.9 +/- 2.5 years of age. Photosensitivity appears around puberty and may disappear around 24 years of age. Photosensitive epilepsy is easily and rapidly controlled by VPA.

Adolescent↗
PubMed1997

Persistence of photosensitivity.

PURPOSE: One hundred patients with photosensitive epilepsy were investigated as part of an ongoing follow-up study. Average duration of follow-up was 14 years; mean age at follow-up was 27 years. METHODS: All patients were EEG investigated using a standard technique of intermittent photic stimulation (IPS). The presence of a photoparoxysmal response (PPR) or a degraded PPR indicated the presence of photosensitivity. RESULTS: Seventy-seven patients became seizure free. Of the untreated patients, photosensitivity disappeared in 14 patients but was present in 32 patients. Of the patients who were treated, 31 showed evidence of PPRs or degraded PPRs, but 23 patients no longer showed evidence of photosensitivity. Thirty-two mothers had 67 children during the follow-up period. Thirteen have so far proved to be sensitive to IPS in the laboratory and four have also had photosensitive seizures induced in the outside environment. Nine of the children have been found not to be photosensitive nor have they had seizures. CONCLUSIONS: This study suggests that photosensitivity persists in at least two thirds of patients with photosensitive epilepsy and that valproate is effective in controlling this photosensitivity.

Adolescent↗
PubMed2006

Low-intensity photosensitization may enhance RecA production.

Three bacterial strains-Escherichia coli, Acinetobacter calcoaceticus, and the A. calcoaceticus RecA- mutant-underwent photosensitization by a low-concentration (0.73 micromol/L) tetramethyl pyridyl porphine (a cationic hydrophylic photosensitizer) and a 4-J/cm2 dose of 407 to 420 nm blue light. The viability of the first two strains decreased by approximately 60%. and that of the RecA- strain decreased by 90%. Increasing the amount of photosensitizer to 14.6 micromol/L at the same dose of blue light resulted in a 95% to 98% decrease in viability of the three strains. Very little damage to the bacterial DNA was observed after this treatment. Increasing the concentration photosensitizer under the same illumination conditions also resulted in very little damage to the DNA. Western blotting demonstrated that the low photosensitization procedures enhance RecA production for mending the damaged chromosomal DNA. RecA production as a result of low-dose photosensitization was confirmed and demonstrated by immunofluorescent staining and gold immunolabeling. Although DNA is not the primary target for photosensitization, this process of RecA production may provide a certain degree of DNA mending and may also affect the survival of bacterial cells on low-intensity photosensitization.

Acinetobacter calcoaceticus↗
PubMed1993

Lysosomes, a key target of hydrophobic photosensitizers proposed for photochemotherapeutic applications.

Despite their important biological activity, lysosomes have been generally neglected as important primary targets of photosensitizers, because they are not easily accessible for experiments. This paper reviews factors favoring the localization of photosensitizers in lysosomes and the various experimental approaches which have been used so far for the characterization of the lysosomal staining by various photosensitizing dyes, including porphyrins, chlorins and phenoxazines. The experimental difficulties observed in combining several in vitro techniques for the unambiguous demonstration of lysosomal targeting are examined. New data on tetraphenylporphine derivatives and a pyropheophorbide, as well as previous data on photofrin II, are presented to illustrate the advantages and possibilities of microspectrofluorometry in the study of photosensitizer localization in single living cells. Both spectral and topographic information available from areas smaller than 1 microns2 make it possible to characterize fairly specific sites of localization through the use of specific and vital fluorescent probes of lysosomes, such as Lucifer Yellow. It is also shown by microspectrofluorometry on single living cells that the chronology of the photosensitized reactions induced by specific or unspecific lysosomal photosensitizers can be easily followed. The photosensitized lipofuscin formation observed at the plasma membrane level with the lysosomotropic tetraphenylporphine supports the contention that it is very rare to find a truly specific lysosomal photosensitizer.

Cells, Cultured↗
PubMed2005

Porphyrin-related photosensitizers for cancer imaging and therapeutic applications.

A photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has recently been approved for diagnosis of bladder cancer. The photosensitizers used are in most cases based on the porphyrin structure. These photosensitizers generally accumulate in cancer tissues to a higher extent than in the surrounding tissues and their fluorescing properties may be utilized for cancer detection. The photosensitizers may be chemically synthesized or induced endogenously by an intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) or 5-ALA esters. The therapeutic effect is based on the formation of reactive oxygen species (ROS) upon activation of the photosensitizer by light. Singlet oxygen is assumed to be the most important ROS for the therapeutic outcome. The fluorescing properties of the photosensitizers can be used to evaluate their intracellular localization and treatment effects. Some photosensitizers localize intracellularly in endocytic vesicles and upon light exposure induce a release of the contents of these vesicles, including externally added macromolecules, into the cytosol. This is the basis for a novel method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins, immunotoxins, gene-encoding plasmids, adenovirus, peptide-nucleic acids and the chemotherapeutic drug bleomycin. The background and present status of PDT, FD and PCI are reviewed.

Animals↗
PubMed2001

Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction.

A noninvasive in situ fluorescence-based method for the quantification of the photosensitizer chloroaluminum disulfonated phthalocyanine was compared to the highly accurate but nonreal time ex vivo spectrofluorometry method. Our in vivo fluorescence technique is designed to allow real-time assessment of photosensitizer in tumor and normal tissues and therefore temporally optimal light delivery. Laser-induced fluorescence was used to measure photosensitizer concentration from multiple microscopic regions of tissue. Ex vivo chemical extraction was used to quantify photosensitizer concentration in the same volume of tissue. The amount of photosensitizer in the vascular and/or parenchymal compartments of skeletal muscle and liver was determined by quantifying fluorescent signal in vivo, ex vivo and after blood removal. Confocal microscopy was used to spatially document photosensitizer localization 30 min and 24 h after delivery. While a linear correlation can exist between the fluorescence intensity measured by our fiber-optic bundle system and actual tissue concentration, temporal changes to this calibration line exist as the photosensitizer changes its partitioning fraction between the blood (vasculature) and the tissue parenchyma. In situ photosensitizer fluorescence microsampling (dosimetry) systems can be performed in real time and linearly correlated to actual tissue concentration with minimal intertissue variance. Tissue-specific differences may require temporal alterations in the calibration.

Animals↗
PubMed1996

Photosensitivity associated with antipsychotics, antidepressants and anxiolytics.

Photosensitivity reactions evoked by systemic agents are the result of the effects of the agent combined with subsequent exposure to light. Photosensitivity induced by exogenous parenteral agents accounts for an increasing portion of the total undesirable effects caused by environmental chemicals. The exponential increase in the number of new drugs introduced each year may be one of the factors explaining the increased number of reports describing photosensitivity induced by exogenous agents. There are many reports of photosensitivity caused by antipsychotic and antidepressant agents. Although the majority of the research was focused on the photosensitising potential of chlorpromazine, other antipsychotics and antidepressants have been shown to cause cutaneous photosensitivity. An extensive drug history must be taken whenever a patient presents with a reaction limited to, or accentuated in, light-exposed areas. It should be remembered that these reactions may present with a wide morphological spectrum ranging from sunburn-like responses to eczematous, lichenoid and even bullous lesions, resembling porphyria cutanea tarda. In order to properly diagnose photosensitivity to systemic drugs it is important to prove photosensitivity by phototesting and to rule out other causes of systemic photosensitivity such as systemic lupus erythematosus and porphyria cutanea tarda.

Anti-Anxiety Agents↗
PubMedDate not supplied

[Approaches to the targeted intracellular delivery of photosensitizers in order to enhance their efficacy and cell specificity].

The main physicochemical properties of photosensitizers used in the photodynamic therapy of cancer and their subcellular distribution after in vitro and in vivo administration were analyzed. It was shown that the effect of photosensitizers is realized at very short distances from the sites of their intracellular localization, and the sensitivities of different cellular compartments to the photocytotoxic action of photosensitizers are different. The necessity of intranuclear delivery of photosensitizers into the nuclei of target cells in order to enhance their efficacy and cell specificity was shown and the available approaches to the targeted delivery of photosensitizers were analyzed. The mechanisms of nucleocytoplasmic transport through the nuclear pore complex, which can be used for the delivery of photosensitizers inward the nucleus, are reviewed. Different modular transporters for photosensitizers comprising (i) a ligand module, which binds to an internalizable receptor overexpressed on the target cells, (ii) an intracellular localization signal, (iii) a carrier module, and (iv) an endosomolytic module were characterized. All these modules were shown to be fully functional within the chimeric polypeptide and the polypeptide as a whole. A significant enhancement of photocytotoxicity and cell specificity of photosensitizers delivered by these transporters were demonstrated. The transporters described represent a new generation of pharmaceuticals which can be widely used for targeted drug delivery.

Animals↗
PubMed1991

Role of iron in the photosensitization by uroporphyrin.

The role of iron in the mechanism of photosensitivity due to uroporphyrin was investigated. There is frequently increased levels of Fe in the serum from patients with porphyria cutanea tarda, where the photosensitivity is due to uroporphyrin. It has been reported that H2O2 has a major role in the uroporphyrin induced photosensitivity. Hence we examined the hypothesis that Fe would catalyze the production of OH from H2O2 and the OH thus formed may have a significant role in the uroporphyrin photosensitivity. This was examined by studying the effects of the Fe chelating compound deferoxamine in an in vitro system. Our results show that deferoxamine inhibited the uroporphyrin photosensitivity, but not the photosensitivity due to protoporphyrin. This indicates that Fe may play a role in the uroporphyrin photosensitization in the skin, by accelerating the formation of OH, which may be a major reactive species responsible for the photosensitization in porphyria cutanea tarda.

Animals↗
PubMed1992

Photorefractory Harris' sparrows (Zonotrichia querula) exposed to a winter-like daylength gradually regain photosensitivity after a lag.

The time course of regaining photosensitivity was monitored in intact and in castrated Harris' sparrows (Zonotrichia querula) held on short days. Measured endpoints, assumed to be equivalent indicators of the photosensitive state, were photoinduced testicular growth in intact males and a photoinduced elevation in plasma LH (luteinizing hormone) concentration in castrated males. Intact males were initially photorefractory when they were moved from long days to short days, and they remained so for at least 3 weeks thereafter. Photosensitivity was partially restored between Weeks 3 and 5 on short days and then gradually increased to a maximum by Week 13. No further change was detected through Week 25 on short days, when the experiment ended. Castrated males, also photorefractory when moved from long days to short days, regained photosensitivity as early as Week 7 on short days, but not uniformly until Week 16. As reflected by linear regression analysis, recovery of photosensitivity was a gradual process through Week 22 on short days, when the experiment ended. Discrepancies between intact and castrated males raise the possibility that the measured endpoints are not equivalent indicators of the photosensitive state. In accordance with an earlier report (Wilson, 1990), recovery of photosensitivity in castrated Harris' sparrows held on short days was not signaled by a spontaneous increase in plasma LH concentration. Indeed, plasma LH concentrations of castrated males remained suppressed even after photosensitivity had been fully restored in intact males.

Animals↗
PubMed1989

Testosterone induction of song in photosensitive and photorefractory male sparrows.

Song in male songbirds is activated by the sex steroid testosterone (T). Using male song sparrows (Melospiza melodia), we compared effects of T in the normal spring state of photosensitivity (i.e., when the pituitary-gonadal axis is sensitive to stimulation by increasing daylength) and in the late summer-early fall state of photorefractoriness (i.e., when they are insensitive to increasing daylength). Photosensitive males experienced short days for 8 weeks and then long days for another 22 weeks to induce photorefractoriness. T implants were given to the birds twice, first when on short days and photosensitive, and second when on long days and photorefractory. Song rates were compared among 5 conditions: (1) photosensitive, short days, low T titers; (2) photosensitive, short days, high T titers; (3) photosensitive, long days, high T titers; (4) photorefractory, long days, low T titers; and (5) photorefractory, long days, high T titers. Plasma levels of T were monitored throughout the experiment by radioimmunoassay. T was equally effective in inducing song in both the photosensitive and photorefractory conditions. Thus, no seasonal change was found in the sensitivity to hormone action of the neural target sites mediating this behavior in song sparrows. Photosensitive birds sang at a higher rate when on long days than when on short days, however, even though there was no concomitant increase in plasma levels of T. This finding suggests that environmental factors can alter the expression of song activated by similar levels of T.

Animals↗
PubMed2003

Photochemical characterization of water samples from Minnesota and Vermont sites with malformed frogs: potential influence of photosensitization by singlet molecular oxygen (1O(2)) and free radicals on aquatic toxicity.

Environmental pollutants activated by UV sunlight may have contributed to the recent decline in frog populations and the concomitant increase in malformations in the USA and abroad. UV radiation is able to mutate DNA and to initiate photosensitization processes that generate mutagenic and biologically disruptive oxygen transients. We have examined water from selected sites in Minnesota and Vermont using singlet molecular oxygen (1O(2)), detected by its phosphorescence and free radicals detected by spin trapping, as markers for photosensitization. Water from a pond in Minnesota with malformed frogs, which also causes malformations in the laboratory, photosensitized more 1O(2), even though it absorbed less UV light compared to water from a site that did not cause malformations. This suggested that unknown natural or pollutant agents were present, and that photosensitization may be involved. Although UV irradiation of the two Minnesota water samples in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) revealed the presence of the DMPO/*OH, DMPO/*H(e(aq)-) and DMPO/*C(unknown) adducts there were no qualitative or quantitative differences between them. We also examined water samples from several sites in Vermont, and compared them by measuring the quantum yield of 1O(2) photosensitization. While all the Vermont samples produced a small amount of 1O(2), there was no clear correlation with the incidence of frog malformations. However, the samples differed strongly in absorption spectra and the ability to quench 1O(2). These factors may determine how much UV light is absorbed and converted into chemical reactions. Our results show that photochemical characterization of 1O(2) photosensitization is possible in untreated natural water samples. Photosensitization falls into the category of global factors that may be closely associated with the effects of UV irradiation of the Earth's environments. Thus, photosensitization might be an important component in global amphibian malformation and decline. The observation of 1O(2) emission directly from natural water may also provide new opportunities to investigate the involvement of 1O(2) in other complex environmental processes.

Animals↗
PubMed2005

Headache due to photosensitive magnesium depletion.

Clinical and paraclinical data (visual stress tests, electroencephalographic and cerebrovascular photic driving, visual evoked potentials) demonstrate that the concept of photosensitive headache is fully justified. The interictal hallmark of photosensitive cephalalgic patients is potentiation (or sensitization) instead of habituation. The aetiopathogenic mechanisms of photosensitive headache associate hypofunction of the biological clock and magnesium depletion. The new concept of headache due to photosensitive magnesium depletion seems justified. It appears logical to add the treatments of magnesium depletion and of photosensitivity to classical treatment of headache. Prophylactic magnesium treatment relies on atoxic nutritional magnesium supplementation in case of primary magnesium deficiency. Pharmacological doses of parenteral magnesium may be used but may induce toxicity. Therefore it is necessary to know the therapeutic index of magnesium compound used: the larger its value, the greater the safety margin. Treatment of photosensitivity uses various types of < >: darkness therapy through physiologic, psychotherapic, physiotherapic, pharmacologic stimulating techniques and substitutive darkness therapy through palliative treatment. Melatonin is only a partial substitutive treatment of photosensitivity. A new model of photosensitive magnesium depletion with potentiation should be a useful tool for discriminating the most efficient gent.

Biological Clocks↗