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Fukuoka Igaku Zasshi = Hukuoka Acta... May 2015Yusho incident is an unprecedented mass food poisoning that occurred in the western area of Japan in 1968. It was caused by the ingestion of rice bran oil contaminated... (Review)
Review
Yusho incident is an unprecedented mass food poisoning that occurred in the western area of Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations in company with systemic, ophthalmological, and mucosal symptoms for a long period. Since the outbreak of Yusho, the Study Group of Yusho has been conducting annual medical check-ups on Yusho victims. We describe here the latest research findings of chronic dioxin-induced toxicity to Yusho patients and the mechanisms of toxicities of dioxins through the aryl hydrocarbon receptor (AhR) pathway. High amounts of PCBs and PCDFs are still present in a number of patients with Yusho. The patients have persistent various symptoms, some of which were significantly associated with blood levels of PCBs, dioxins, or dioxin-like compounds. The adverse effects on the next generation are also found. According to the findings of recent basic studies, the biological and toxicological effects mediated by the AhR system have been becoming clear; therefore, the therapeutic interventions may be found in the near future.
Topics: Female; Humans; Male; Porphyrias
PubMed: 26226682
DOI: No ID Found -
Orphanet Journal of Rare Diseases Apr 2021This study used quantitative and qualitative research methods to analyze how acute hepatic porphyria (AHP) affects patients with varying annualized porphyria attack...
BACKGROUND
This study used quantitative and qualitative research methods to analyze how acute hepatic porphyria (AHP) affects patients with varying annualized porphyria attack rates. The overall impact of AHP on patients and caregivers, including their quality of life, was explored. The nature and treatment of acute attacks, experiences of long-term heme arginate treatment and access to other appropriate treatment, and the extent of and treatment for chronic symptoms were also investigated within this study.
METHODS
Patient and caregiver data were collected via an online survey of members of the British Porphyria Association, followed by an optional 1-h telephone interview.
RESULTS
Thirty-eight patients and 10 caregivers responded to the survey. Of those, 10 patients and three caregivers completed follow-up interviews. Overall, 19 patients (50%) had experienced an acute attack within the previous 2 years, and the severity and types of symptoms experienced during or between acute attacks varied considerably. There were no clear definitions among patients for 'mild' or 'severe' attacks. Treatments and treatment settings used to manage attacks also varied. Following unsatisfactory care experiences at hospitals, some patients reported avoiding further hospital services for later attacks. Therefore, using settings of care as a measure of attack severity should be avoided. Ninety-four percent of patients also experienced chronic symptoms, which were as varied as acute attacks. Pain was the predominant chronic symptom and was managed with opioids in severe cases. Regardless of AAR, porphyria heavily impacted the daily lives of patients and caregivers. Although patients experiencing frequent attacks generally endured a greater impact on their daily life, patients with less frequent attacks also experienced impacts on all domains (social, leisure activities, relationship with family, relationships, psychological wellbeing, finances, employment, and study). Caregivers were most affected in the finance, relationships with family, and employment domains, and just over half of the caregivers reported a moderate impact on their psychological wellbeing.
CONCLUSIONS/IMPLICATIONS
The burden of illness with AHP is high across all patients, regardless of frequency of attacks, and AHP negatively affects patients and caregivers alike.
Topics: Caregivers; Humans; Porphobilinogen Synthase; Porphyrias, Hepatic; Quality of Life; United Kingdom
PubMed: 33902669
DOI: 10.1186/s13023-021-01816-2 -
Tidsskrift For Den Norske Laegeforening... Oct 2003
Topics: Acute Disease; Contraindications; Cytochrome P-450 Enzyme System; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Internet; Norway; Pharmaceutical Preparations; Porphyrias
PubMed: 14600718
DOI: No ID Found -
Hyperhomocysteinemia in acute hepatic porphyria (AHP) and implications for treatment with givosiran.Expert Review of Gastroenterology &... Sep 2022Homocysteine is a sulfur-containing amino acid formed in the intermediary metabolism of methionine. Amino acid metabolism and heme biosynthesis pathways are complexly...
INTRODUCTION
Homocysteine is a sulfur-containing amino acid formed in the intermediary metabolism of methionine. Amino acid metabolism and heme biosynthesis pathways are complexly intertwined. Plasma homocysteine elevation, (HHcy), has been reported in patients with acute hepatic porphyria (AHP), a family of rare genetic disorders caused by defects in hepatic heme biosynthesis.
AREAS COVERED
This article summarizes published case series in which givosiran, a subcutaneously administered small interfering RNA approved for AHP treatment, appeared to exacerbate dysregulated homocysteine metabolism in patients with AHP. A comprehensive exploratory analysis of ENVISION trial data demonstrated that on a population level, givosiran increased homocysteine but with wide interpatient variations, and there is no proof of correlations between HHcy and changes in efficacy or safety of givosiran.
EXPERT OPINION
The strong correlation and co-increase of homocysteine and methionine suggest that HHcy associated with givosiran is likely attributable to the impaired trans-sulfuration pathway catalyzed by cystathionine β-synthase, which uses vitamin B6 as a cofactor. Data-based consensus supports monitoring total plasma homocysteine and vitamin B6, B12, and folate levels before and during givosiran treatment; supplementing with pyridoxine/vitamin B6 in patients with homocysteine levels >100 μmol/L; and involving patients with homocysteine levels >30 μmol/L in decisions to supplement.
Topics: Humans; Cystathionine beta-Synthase; Folic Acid; Heme; Homocysteine; Hyperhomocysteinemia; Methionine; Porphyrias, Hepatic; Pyridoxine; RNA, Small Interfering; Sulfur; Vitamin B 6; Clinical Trials as Topic
PubMed: 35929959
DOI: 10.1080/17474124.2022.2110469 -
The American Journal of the Medical... Aug 2021Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experience acute neurovisceral attacks, chronic symptoms, and long-term... (Review)
Review
Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experience acute neurovisceral attacks, chronic symptoms, and long-term complications. Diagnostic biochemical testing is widely available and effective, but a substantial time from symptom onset to diagnosis often delays treatment and increases morbidity. A panel of laboratory scientists and clinical AHP specialists collaborated to produce recommendations on how to enhance biochemical diagnosis of AHP in the USA. AHP should be considered in the differential diagnosis of unexplained abdominal pain, the most common symptom, soon after excluding common causes. Measurement of porphobilinogen (PBG) and porphyrins in a random urine sample, with results normalized to creatinine, is recommended as an effective and cost-efficient initial test for AHP. Delta-aminolevulinic acid testing may be included but is not essential. The optimal time to collect a urine sample is during an attack. Substantial PBG elevation confirms an AHP diagnosis and allows for prompt treatment initiation. Additional testing can determine AHP subtype and identify at-risk family members. Increased awareness of AHP and correct diagnostic methods will reduce diagnostic delay and improve patient outcomes.
Topics: Humans; Physicians, Primary Care; Porphobilinogen Synthase; Porphyrias, Hepatic; Practice Guidelines as Topic
PubMed: 33865828
DOI: 10.1016/j.amjms.2021.03.004 -
Anaesthesia Jan 1968
Topics: Humans; Porphyrias
PubMed: 5638205
DOI: 10.1111/j.1365-2044.1968.tb00023.x -
British Medical Journal Mar 1958
Topics: Porphyrias
PubMed: 13510759
DOI: 10.1136/bmj.1.5071.640 -
British Medical Journal Dec 1953
Topics: Porphyrias
PubMed: 13106414
DOI: 10.1136/bmj.2.4849.1291 -
Postgraduate Medical Journal Apr 1956
Topics: Humans; Porphyrias
PubMed: 13388974
DOI: 10.1136/pgmj.32.366.186 -
International Journal of Molecular... Jan 2021Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and... (Review)
Review
Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho.
Topics: Animals; Dioxins; Humans; Porphyrias; Reactive Oxygen Species; Receptors, Aryl Hydrocarbon; Rice Bran Oil
PubMed: 33445793
DOI: 10.3390/ijms22020708