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Photodermatology, Photoimmunology &... Jan 2020Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported;...
BACKGROUND
Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported; however, data regarding this rare disorder are scarce.
PURPOSE
To evaluate the characteristics of acquired EPP.
METHODS
A comprehensive search of PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases was performed by three reviewers. Studies describing patients with acquired EPP were included. Additionally, we present an index case of a 26-year-old patient who acquired clinically and biochemically typical EPP in association with myelodysplastic syndrome (MDS).
RESULTS
We included 20 case reports describing 20 patients. Most (80%) patients were male of mean age 58 ± 13 years. In all patients, acquired EPP was associated with hematological disease, most commonly MDS (85%) followed by myeloproliferative disease (10%). In 86% of cases, hematological disease led to abnormality or somatic mutation in chromosome 18q (the locus of the ferrochelatase gene). The mean erythrocyte protoporphyrin IX concentration was very high (4286 μg/dL). Most (90%) patients presented with photosensitivity, 20% experienced blistering, and 25% presented with hepatic insufficiency, both uncommon in EPP. In 55% of patients, hematological disease was diagnosed after occurrence of cutaneous symptoms. Beta-carotene led to partial control of symptoms in 5 patients and resolution in another patient. Azacitidine treatment of MDS led to resolution of cutaneous symptoms in three patients.
CONCLUSION
We present the distinct features of acquired EPP and highlight that any patient presenting with new-onset photosensitivity, irrespective of age should be evaluated for porphyria.
Topics: Adult; Aged; Azacitidine; Chromosomes, Human, Pair 18; Erythrocytes; Female; Ferrochelatase; Genetic Loci; Humans; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Photosensitivity Disorders; Protoporphyria, Erythropoietic; Protoporphyrins; beta Carotene
PubMed: 31374130
DOI: 10.1111/phpp.12501 -
Phytomedicine : International Journal... Jul 2019Photoactivity, though known for centuries, is only recently shifting back into focus as a treatment option against cancer and microbial infections. The external factor...
BACKGROUND
Photoactivity, though known for centuries, is only recently shifting back into focus as a treatment option against cancer and microbial infections. The external factor light is the ingenious key-component of this therapy: Since light activates the drug locally, a high level of selectivity is reached and side effects are avoided. The first reported photoactive medicines were plant extracts. Synthetic entities (so-called photosensitizers PSs), however, paved the route towards the clinical approval of the so-called photodynamic therapy (PDT), and thus natural PSs took a backseat in the past.
HYPOTHESIS
Many isolated bioactive phytochemicals hold a hidden photoactive potential, which is overlooked due to the reduced common awareness of photoactivity.
METHODS
A systematic review of reported natural PSs and their supposed medicinal application was conducted by employing PubMed, Scifinder, and Web of Science. The identified photoactive natural products were compiled including information about their natural sources, their photoyield, and their pharmacological application. Furthermore, the common chemical scaffolds of natural PS are shown to enable the reader to recognize potentially overlooked natural PSs.
RESULTS
The literature review revealed over 100 natural PS, excluding porphyrins. The PSs were classified according to their scaffold. Thereby it was shown that some PS-scaffolds were analyzed in a detailed way, while other classes were only scarcely investigated, which leaves space for future discoveries. In addition, the literature revealed that many PSs are phytoalexins, thus the selection of the starting material significantly matters in order to find new PSs.
CONCLUSION
Photoactive principles are ubiquitous and can be found in various plant extracts. With the increasing availability of light-irradiation setups for the identification of photoactive natural products, we anticipate the discovery of many new natural PSs in the near future. With the accumulation of chemically diverse PSs, PDT itself might finally reach its clinical breakthrough as a promising alternative treatment against multi-resistant microbes and cancer types.
Topics: Biological Products; Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Phytochemicals; Sesquiterpenes; Phytoalexins
PubMed: 31257117
DOI: 10.1016/j.phymed.2019.152985 -
BMC Cancer Jun 2019Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk.
METHODS
Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations.
RESULTS
A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04-1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89-1.15), supplemental (1.02, 95% CI: 0.91-1.13), or total (0.97, 95% CI: 0.82-1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01-1.47), but not for ferritin (1.13, 95% CI: 0.78-1.62), transferrin saturation (1.16, 95% CI: 0.91-1.47), or total iron-binding capacity (1.10, 95% CI: 0.97-1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both P < 0.05).
CONCLUSIONS
Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinogenesis; Female; Ferritins; Heme; Humans; Iron; Iron, Dietary; Meat; Middle Aged; Nutritional Status; Postmenopause; Risk; Transferrin; Young Adult
PubMed: 31170936
DOI: 10.1186/s12885-019-5642-0 -
Current Medicinal Chemistry 2019Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture...
Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.
Topics: Animals; Anti-Inflammatory Agents; Biological Products; Coumarins; Edema; Plants, Medicinal; Porphyrins; Structure-Activity Relationship
PubMed: 31119997
DOI: 10.2174/0929867325666190523123357 -
Acta Neurochirurgica Jun 20195-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of...
BACKGROUND
5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of resection, and improves patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial and the role of 5-ALA-guided resection of these tumors is not clear, we sought to perform a comprehensive literature review on this topic.
METHODS
A systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 19 eligible publications encompassing 175 5-ALA-guided operations on pediatric brain tumors. To prevent bias, publications were revised independently by two authors.
RESULTS
We found that 5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. One important finding is that when 5-ALA-guided resections were considered helpful, the degree of resection was higher than is cases where it was not helpful. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae.
CONCLUSION
5-ALA could play a role in resection of pediatric brain tumors. However, further prospective clinical trials are needed.
Topics: Aminolevulinic Acid; Brain Neoplasms; Child; Female; Glioma; Humans; Male; Photosensitizing Agents; Postoperative Complications; Surgery, Computer-Assisted
PubMed: 30989383
DOI: 10.1007/s00701-019-03898-1 -
Nutrition Research (New York, N.Y.) Nov 2018Several epidemiological studies investigated the relationship between dietary intake of essential trace elements and the risk of esophageal cancer (EC), yielding... (Meta-Analysis)
Meta-Analysis
Several epidemiological studies investigated the relationship between dietary intake of essential trace elements and the risk of esophageal cancer (EC), yielding inconsistent results. We therefore conducted a systematic meta-analysis to investigate and quantify the putative association between the intake of various essential trace elements and the risk of EC. We searched Embase, PubMed, and Web of Science for eligible articles published through April 2018 reporting the odds ratio (OR) with 95% confidence interval (95% CI). Pooled results were then calculated using fixed and random effect models. A total of 20 articles containing 4855 cases from 1 387 482 participants were included in our analysis. We found a significant inverse correlation between total iron intake and the risk of EC (OR = 0.81, 95% CI: 0.70-0.94), particularly in Asian populations. A dose-response analysis revealed that each 5 mg/day increase in total iron intake was associated with a 15% reduction in EC risk (OR = 0.85, 95% CI: 0.79-0.92). In contrast, each 1 mg/day increase in heme iron intake was associated with a 21% increase in EC risk (OR = 1.21, 95% CI: 1.02-1.45). Lastly, a pooled risk estimate revealed that each 5 mg/day increase in zinc intake was associated with a 15% reduction in EC risk (OR = 0.85, 95% CI: 0.77-0.93). Taken together, our analysis indicates that increased dietary intake of total iron and zinc, as well as decreased heme iron intake, may be associated with a lower risk of developing esophageal cancer. These findings have important public health implications with respect to preventing this relatively common form of cancer.
Topics: Diet; Esophageal Neoplasms; Heme; Humans; Iron; Iron, Dietary; Risk Factors; Trace Elements; Zinc
PubMed: 30442229
DOI: 10.1016/j.nutres.2018.07.007 -
BMC Women's Health Aug 2018Since the publication over 50 years ago of the alkaline hematin method for quantifying menstrual blood loss (MBL) many new approaches have been developed to assess MBL....
BACKGROUND
Since the publication over 50 years ago of the alkaline hematin method for quantifying menstrual blood loss (MBL) many new approaches have been developed to assess MBL. The aim of this systematic review is to determine for methods of measuring MBL: ability to distinguish between normal and heavy menstrual bleeding (HMB); practicalities and limitations in the research setting; and suitability for diagnosing HMB in routine clinical practice.
METHODS
Embase®™, MEDLINE®, and ClinicalTrials.gov were screened for studies on the development/validation of MBL assessment methods in women with self-perceived HMB, actual HMB or uterine fibroids, or patients undergoing treatment for HMB. Studies using simulated menstrual fluid and those that included women with normal MBL as controls were also eligible for inclusion. Extracted data included study population, results of validation, and advantages/disadvantages of the technique.
RESULTS
Seventy-one studies fulfilled the inclusion criteria. The sensitivity and/or specificity of diagnosing HMB were calculated in 16 studies of methods involving self-perception of MBL (11 pictorial), and in one analysis of the menstrual-fluid-loss (MFL) method; in 13 of these studies the comparator was the gold standard alkaline hematin technique. Sensitivity and specificity values by method were, respectively: MFL model, 89, 98%; pictorial blood loss assessment chart (PBAC), 58-99%, 7.5-89%; menstrual pictogram, 82-96%, 88-94%; models/questionnaires, 59-87%, 62-86%, and complaint of HMB, 74, 74%. The power of methods to identify HMB was also assessed using other analyses such as comparison of average measurements: statistical significance was reported for the PBAC, MFL, subjective complaint, and six questionnaires. In addition, PBAC scores, menstrual pictogram volumes, MFL, pad/tampon count, iron loss, and output from three questionnaires correlated significantly with values from a reference method in at least one study. In general, pictorial methods have been more comprehensively validated than questionnaires and models.
CONCLUSIONS
Every method to assess MBL has limitations. Pictorial methods strike a good balance between ease of use and validated accuracy of MBL determination, and could complement assessment of HMB using quality of life (QoL) in the clinical and research setting.
TRIAL REGISTRATION
PRISMA registration number: CRD42016032956 .
Topics: Adult; Diagnostic Techniques, Obstetrical and Gynecological; Female; Hemin; Humans; Menorrhagia; Middle Aged; Sensitivity and Specificity; Surveys and Questionnaires
PubMed: 30134884
DOI: 10.1186/s12905-018-0627-8 -
American Journal of Reproductive... Feb 2018Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory... (Review)
Review
Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.
Topics: Animals; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Cyclooxygenase 2; Female; Humans; Inflammation; Inflammation Mediators; Metalloporphyrins; Parturition; Pregnancy; Uterus
PubMed: 29076197
DOI: 10.1111/aji.12776 -
Asia Pacific Journal of Clinical... 2017Some potential role of iron overload in the development of diabetes mellitus have been suggested. Our study aimed to systematically assess the association between the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some potential role of iron overload in the development of diabetes mellitus have been suggested. Our study aimed to systematically assess the association between the risk of gestational diabetes mellitus (GDM) and iron intakes/body iron status.
METHODS AND STUDY DESIGN
PubMed and Web of Science were searched for relevant articles. Relative risks (RR) of GDM in relation to dietary iron intakes and body iron stores were pooled with the random-effects model. Weighted mean differences of iron blood markers between GDM and non-GDM individuals were also analyzed.
RESULTS
Twenty-five studies were included in the qualitative analysis, and 23 studies with 29,378 participants and 3,034 GDM patients were included in the quantitative analysis. Dietary intake of heme iron was significantly associated with GDM risk (RR=1.65, 95% CI: 1.28 to 2.12), and the pooled RR for each 1mg/day increment of heme iron intake was 1.38 (95% CI: 1.19 to 1.61). No association between GDM and the intakes of nonheme iron, total iron, or supplemental iron was detected. Body iron stores, as represented by serum ferritin level, were correlated with GDM risk (RR=1.64, 95% CI: 1.27 to 2.11). Moreover, the concentrations of both serum ferritin and serum iron were increased in GDM patients, compared with non-GDM individuals.
CONCLUSIONS
Increased dietary intake of heme iron and body iron status are positively associated with the risk of GDM development in pregnant women. Future studies are warranted to better understand the role of iron in GDM development.
Topics: Diabetes, Gestational; Female; Heme; Humans; Iron, Dietary; Nutritional Status; Pregnancy
PubMed: 28917236
DOI: 10.6133/apjcn.022017.09 -
Journal of Investigative and Clinical... Feb 2018The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and... (Review)
Review
AIM
The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and head and neck squamous cell carcinoma (HNSCC).
METHODS
From 1985 to 2015, PubMed/Medline, Google Scholar, EMBASE, and ISI Web of Knowledge were searched using different combinations of the following key words: PDT, oral precancer, leukoplakia, erythroplakia, erythroleukoplakia, verrucous hyperplasia, oral submucous fibrosis, and HNSCC. Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded.
RESULTS
Twenty-six studies were included in the present study. The number of patients ranged from 2 to 147, with a mean age of 50-67 years. The reported numbers of PMDS and HNSCC ranged between 5 and 225. Photosensitizers used were aminolevulinic acid, meta-tetrahydroxyphenylchlorin, Foscan, hematoporphyrin derivatives, Photofrin, Photosan, and chlorine-e6. Laser wavelength, power density, irradiation duration were 585-652 nm, 50-500 mW/cm , and 1-143 minutes, respectively. Complete, partial, and no response to PDT was found in 22.58%-100%, 4%-66%, and 0%-38.70% of PMDS, respectively, and 16%-100% of complete response in HNSCC patients.
CONCLUSION
PDT is effective in the management of PMDS and HNSCC.
Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Chlorophyllides; Databases, Factual; Dihematoporphyrin Ether; Erythroplasia; Head and Neck Neoplasms; Hematoporphyrins; Humans; Hyperplasia; Indoles; Laser Therapy; Lasers; Leukoplakia; Leukoplakia, Oral; Mesoporphyrins; Oral Submucous Fibrosis; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome
PubMed: 28480637
DOI: 10.1111/jicd.12270