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Haematologica Jul 2021
Topics: 5-Aminolevulinate Synthetase; Endopeptidase Clp; Humans; Iron; Mutation; Protoporphyria, Erythropoietic; Severity of Illness Index
PubMed: 33596641
DOI: 10.3324/haematol.2020.272450 -
Journal of Photochemistry and... Mar 2021In the knowledge that human ultra-weak photon emission (UPE) is mainly due to the metabolic oxidative stress processes that the skin cells undergo in the presence of... (Review)
Review
In the knowledge that human ultra-weak photon emission (UPE) is mainly due to the metabolic oxidative stress processes that the skin cells undergo in the presence of reactive oxygen species (ROS), external stressors (like UV radiation), but also internal stressors (like diseases or brain activity) might strongly influence the UPE. This manuscript revises the scientific advances focused on the influence of internal factors on the human UPE. According to literature, the UPE seems to be influenced by some diseases (including diabetes, hemiparesis, protoporphyria, or a typical cold), and even by the cerebral intention/relaxation (brain activity/meditation). These allow to consider UPE as a natural and promising non-invasive spectroscopic tool for helping during the diagnosis of a variety of illnesses or stress- / mood-state disorders. Nonetheless, further research is required for answering some still unresolved controversial points.
Topics: Brain; Diabetes Mellitus; Humans; In Vitro Techniques; Luminescent Measurements; Meditation; Paresis; Photons; Reactive Oxygen Species; Skin; Ultraviolet Rays
PubMed: 33540236
DOI: 10.1016/j.jphotobiol.2021.112141 -
Surgical Case Reports Jan 2021Erythropoietic protoporphyria (EPP) is a rare disorder of heme synthesis. Patients with EPP mainly show symptoms of photosensitivity, but approximately 20% of EPPs are...
BACKGROUND
Erythropoietic protoporphyria (EPP) is a rare disorder of heme synthesis. Patients with EPP mainly show symptoms of photosensitivity, but approximately 20% of EPPs are associated with the liver-related complications. We report a case of breast cancer in a 48-year-old female patient with EPP in whom meticulous perioperative management was required in order to avoid complications resulting from this disease.
CASE PRESENTATION
The patient was diagnosed with EPP at the age of 33 and had a rich family history of the disease. For right breast cancer initially considered as TisN0M0 (Stage 0), the right mastectomy and sentinel lymph node biopsy were performed, while the final stage was pT1bN0M0, pStage I. In the perioperative period, we limited the drug use and monitored light wavelength measurements. Besides, we covered surgical lights, headlights, and laryngoscope's light with a special polyimide film that filtered the wavelength of light causing dermal photosensitivity. After the surgery, any emerging complications were closely monitored.
CONCLUSIONS
The surgery, internal medicine, anesthesiology, and operation departments undertook all possible measures through close cooperation to ensure a safe surgery for the patient with a rare condition.
PubMed: 33400006
DOI: 10.1186/s40792-020-01068-5 -
Hematology. American Society of... Dec 2020The porphyrias are a family of metabolic disorders caused by defects in the activity of one of the enzymes in the heme biosynthetic pathway. Acute intermittent porphyria...
The porphyrias are a family of metabolic disorders caused by defects in the activity of one of the enzymes in the heme biosynthetic pathway. Acute intermittent porphyria (AIP), caused by autosomal dominant mutations in the gene encoding hydroxymethylbilane synthase, can lead to hepatocyte overaccumulation and systemic distribution of the proximal porphyrin precursors, 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA and PBG are toxic to neurons and extrahepatic tissue and cause the neurovisceral clinical manifestations of AIP. Management of AIP includes awareness and avoidance of triggering factors, infusions of hemin for severe acute attacks, and, if indicated for chronic suppressive therapy, maintenance treatment with hemin or givosiran, a small interfering RNA molecule that antagonizes ALA synthase 1 transcripts. Erythropoietic protoporphyria (EPP) is most commonly caused by autosomal recessive mutations in the gene encoding ferrochelatase (FECH), the heme pathway terminal enzyme. FECH deficiency leads to erythrocyte overaccumulation and high plasma levels of lipophilic protoporphyrins that photoactivate in the skin, causing burning pain and erythema. Protoporphyrins excreted in the bile can cause gallstones, cholestasis, fibrosis, and ultimately liver failure. Management of EPP includes skin protection and afamelanotide, an α-melanocyte stimulating hormone analog that increases melanin pigment and reduces photoactivation. Liver transplantation may be necessary for severe EPP-induced liver complications. Because AIP and EPP arise from defects in the heme biosynthetic pathway, hematologists are often consulted to evaluate and manage suspected or proven porphyrias. A working knowledge of these disorders increases our confidence and effectiveness as consultants and medical providers.
Topics: Adult; Disease Management; Female; Heme; Humans; Mutation; Porphyria, Acute Intermittent; Protoporphyria, Erythropoietic; Young Adult
PubMed: 33275677
DOI: 10.1182/hematology.2020000124 -
Journal of the American Veterinary... Dec 2020A 6-month-old sexually intact male Clumber Spaniel was evaluated because of small stature, recurrent dermatitis of the head, and progressive pigmentary hepatopathy.
CASE DESCRIPTION
A 6-month-old sexually intact male Clumber Spaniel was evaluated because of small stature, recurrent dermatitis of the head, and progressive pigmentary hepatopathy.
CLINICAL FINDINGS
Clinicopathologic findings included nonanemic hypochromic microcytosis, hypocholesterolemia, persistently high serum liver enzyme activities, and anicteric hyperbilirubinemia. Histologic examination of liver biopsy specimens collected when the dog was 6 months and 2 years of age revealed expansion and bridging of portal tracts, occasional centrilobular parenchymal collapse, scattered lymphoplasmacytic infiltrates, and dark red to brown pigment within large aggregates of macrophages, engorged bile canaliculi, and hepatocytes. The pigment failed to stain for the presence of iron, copper, bile, and glycoprotein and, when examined with polarized microscopy, emitted a yellow to green birefringence with occasional Maltese cross configurations. Further analyses confirmed marked porphyrin accumulation in blood, urine, feces, and liver tissue; protoporphyrin accumulation in RBCs and liver tissue; and a signature porphyrin profile and fluorescence peak consistent with erythropoietic protoporphyria. Advanced protoporphyric hepatopathy was diagnosed. The chronic dermatopathy was presumed to reflect protoporphyric photosensitivity.
TREATMENT AND OUTCOME
Management was focused on avoiding conditions known to induce heme synthesis and catabolism, administrating ursodeoxycholic acid and antioxidants -adenosylmethionine and vitamin E, and avoiding sunlight exposure. At follow-up at 4 years of age, the dog was stable without evidence of jaundice but with probable persistent erythropoietic protoporphyria-related solar dermatopathy.
CLINICAL RELEVANCE
Clinical and histologic features of congenital erythropoietic protoporphyria and resultant protoporphyric hepatopathy, the diagnosis, and the successful management of a dog with these conditions over 4 years were described. Veterinarians should consider porphyric syndromes when unusual pigmentary hepatopathies are encountered.
Topics: Animals; Bile; Dog Diseases; Dogs; Liver; Liver Diseases; Male; Protoporphyria, Erythropoietic; Ursodeoxycholic Acid
PubMed: 33226294
DOI: 10.2460/javma.2020.257.11.1148 -
The Indian Journal of Medical Research Nov 2020
Topics: Humans; Liver Diseases; Protoporphyria, Erythropoietic
PubMed: 35345089
DOI: 10.4103/ijmr.IJMR_2254_19 -
Ecotoxicology and Environmental Safety Jan 2021Environmental mercury is a concern for coastal ecosystem health, and exerts adverse effects on human health. Despite the growing body of evidence showing the...
Environmental mercury is a concern for coastal ecosystem health, and exerts adverse effects on human health. Despite the growing body of evidence showing the hepatoprotective roles of curcumin on mercury, the knowledge between the macroscopic descriptions and the actual mechanism(s) underlying these processes is getting larger remains elusive. Herein, mice received single injection of mercuric chloride (HgCl) (5 mg/kg body weight) and/or curcumin (50 mg/kg, body weight, p.o.). Firstly, the results showed curcumin could decline HgCl-induced up-regulated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, we also found that curcumin could suppress inflammatory damage, unbalance of trace elements (including sodium, magnesium, kalium, calcium overload), oxidative burst induced by HgCl, which could be associated with cytochrome P450 (CYP450) signaling. Secondly, we found that curcumin could prevent HgCl-induced cell death both in vivo and in vitro. Furthermore, curcumin significantly increased the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and consequently upregulated the expression of heme oxygenase 1 (HO-1) under HgCl treatment. Meanwhile, inhibition of HO-1 by zinc protoporphyria could abolish the cytoprotective effects of curcumin in HgCl-treated L02 hepatocytes. In conclusion, our data identify that curcumin could enhance Nrf2-mediated HO-1 to upregulate antioxidant ability, which might be associate with CYP450 signaling to suppress liver damage induced by HgCl. The present study further enriches and perfects the mechanism theory of HgCl toxicity and suggest that the CYP450 signaling and Nrf2/HO-1 pathway is important in shedding light on curcumin's hepatoprotective effects in HgCl toxicity.
Topics: Alanine Transaminase; Animals; Antioxidants; Chemical and Drug Induced Liver Injury, Chronic; Curcumin; Cytochrome P-450 Enzyme System; Ecosystem; Hazardous Substances; Heme Oxygenase-1; Hepatocytes; Humans; Mercuric Chloride; Mice; NF-E2-Related Factor 2; Oxidation-Reduction; Oxidative Stress; Protective Agents; Signal Transduction; Up-Regulation
PubMed: 33096358
DOI: 10.1016/j.ecoenv.2020.111426 -
European Journal of Dermatology : EJD Oct 2020Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement.
BACKGROUND
Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement.
OBJECTIVE
To provide epidemiological data of EPP in Italy.
MATERIALS & METHODS
Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017).
RESULTS
In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed ≤10 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67 + 5G > A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one α-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed.
CONCLUSION
These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.
Topics: 5-Aminolevulinate Synthetase; Adult; Cross-Sectional Studies; Female; Ferrochelatase; Genes, Recessive; Genes, X-Linked; Humans; Incidence; Italy; Male; Molecular Epidemiology; Mutation; Prevalence; Prospective Studies; Protoporphyria, Erythropoietic; Retrospective Studies
PubMed: 33021473
DOI: 10.1684/ejd.2020.3880 -
Actas Dermo-sifiliograficas Feb 2021
Topics: Colombia; Ferrochelatase; Humans; Incidence; Prevalence; Protoporphyria, Erythropoietic
PubMed: 32991848
DOI: 10.1016/j.ad.2019.04.019 -
Plastic and Reconstructive Surgery.... Aug 2020
PubMed: 32983808
DOI: 10.1097/GOX.0000000000003066