Genomes of ticks display reductions, to various extents, in genetic coding for enzymes of the haem biosynthetic pathway. Here, we mined available transcriptomes of soft tick species and identified transcripts encoding only half of the enzymes involved in haem biosynthesis. Transcripts identified across most species examined were those coding for porphobilinogen synthase, coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase. Genomic retention of porphobilinogen synthase seems to be soft tick-restricted as no such homologue has been identified in any hard tick species. Bioinformatic mining is thus strongly indicative of the lack of biochemical capacity for de novo haem biosynthesis, suggesting a requirement for dietary haem. In the hard tick Ixodes ricinus, depletion of dietary haem, i.e. serum feeding, leads to oviposition of haem-free eggs, with no apparent embryogenesis and larvae formation. In this work, we show that serum-fed Ornithodoros moubata females, unlike those of I. ricinus, laid haem-containing eggs similarly to blood-fed controls, but only by a small proportion of the serum-fed females. To enhance the effect of dietary haem depletion, O. moubata ticks were serum-fed consecutively as last nymphal instars and females. These females laid eggs with profoundly reduced haem deposits, confirming the host origin of the haem. These data confirm the ability of soft ticks to take up and allocate host haem to their eggs in order to drive reproduction of the ticks.

• Klíčová slova
• Haem biosynthesis, Membrane feeding, Ornithodoros, Parasitism, Porphobilinogen synthase, Soft ticks,
• MeSH
• Argasidae * MeSH
• hem MeSH
• Ixodidae * MeSH
• Ornithodoros * MeSH
• porfobilinogensynthasa MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hem MeSH
• porfobilinogensynthasa MeSH

BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.

• MeSH
• biologické markery moč   MeSH
• dospělí MeSH
• jaterní porfyrie farmakoterapie   patofyziologie   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• porfobilinogensynthasa nedostatek   moč   MeSH
• prospektivní studie MeSH
• recidiva MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• porfobilinogensynthasa MeSH

With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Therefore, an international collaborative with the European Porphyria Network and the National Institutes of Health/National Center for Advancing Translational Sciences/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NCATS/NIDDK)-sponsored Porphyrias Consortium of porphyria diagnostic experts is establishing an online database that will collate biochemical and clinical evidence verifying the pathogenicity of the published and newly identified variants in the AHP-causing genes. The overall goal of the International Porphyria Molecular Diagnostic Collaborative is to determine the pathogenic and benign variants for all eight porphyrias. Here we describe the overall objectives and the initial efforts to validate pathogenic and benign variants in the respective heme biosynthetic genes causing the AHPs.

• Klíčová slova
• acute hepatic porphyrias, benign variants, database, pathologic variants, variant validation,
• MeSH
• akutní intermitentní porfyrie genetika   patofyziologie   MeSH
• databáze faktografické MeSH
• datové kurátorství metody   MeSH
• jaterní porfyrie genetika   patofyziologie   MeSH
• lidé MeSH
• molekulární patologie MeSH
• porfobilinogensynthasa nedostatek   genetika   MeSH
• porfyrie genetika   patofyziologie   MeSH
• virulence genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené státy americké MeSH
• Názvy látek
• porfobilinogensynthasa MeSH

Tetrapyrroles such as chlorophyll and heme are indispensable for life because they are involved in energy fixation and consumption, i.e. photosynthesis and oxidative phosphorylation. In eukaryotes, the tetrapyrrole biosynthetic pathway is shaped by past endosymbioses. We investigated the origins and predicted locations of the enzymes of the heme pathway in the chlorarachniophyte Bigelowiella natans, the cryptophyte Guillardia theta, the "green" dinoflagellate Lepidodinium chlorophorum, and three dinoflagellates with diatom endosymbionts ("dinotoms"): Durinskia baltica, Glenodinium foliaceum and Kryptoperidinium foliaceum. Bigelowiella natans appears to contain two separate heme pathways analogous to those found in Euglena gracilis; one is predicted to be mitochondrial-cytosolic, while the second is predicted to be plastid-located. In the remaining algae, only plastid-type tetrapyrrole synthesis is present, with a single remnant of the mitochondrial-cytosolic pathway, a ferrochelatase of G. theta putatively located in the mitochondrion. The green dinoflagellate contains a single pathway composed of mostly rhodophyte-origin enzymes, and the dinotoms hold two heme pathways of apparently plastidal origin. We suggest that heme pathway enzymes in B. natans and L. chlorophorum share a predominantly rhodophytic origin. This implies the ancient presence of a rhodophyte-derived plastid in the chlorarachniophyte alga, analogous to the green dinoflagellate, or an exceptionally massive horizontal gene transfer.

• MeSH
• biologická evoluce * MeSH
• biosyntetické dráhy * genetika   MeSH
• Cryptophyta klasifikace   genetika   metabolismus   MeSH
• Dinoflagellata klasifikace   genetika   metabolismus   MeSH
• fylogeneze MeSH
• hem metabolismus   MeSH
• porfobilinogensynthasa genetika   metabolismus   MeSH
• rozsivky klasifikace   genetika   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• tetrapyrroly metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hem MeSH
• porfobilinogensynthasa MeSH
• tetrapyrroly MeSH

Ninety children residing in a highly Pb-polluted area near a lead foundry (group E), and 61 children from the control area (group C) were examined and compared. In group E children there were detected significantly increased blood Pb concentrations (girls: 31.6 +/- 16 microgram/100 ml; boys: 38.7 +/- 15.8 microgram/100 ml) in comparison with the control group C children (about 20 microgram/100 ml for both sexes). Regression analysis revealed significantly positive correlation of Pb concentrations in blood with the level of total blood proteins and ALAD, the correlation with A-1AT, alpha-2-M, TRF, and CPL was much less pronounced. Also the correlation of Ca2+ concentrations in blood with blood protein levels was not too marked. On the other hand, the age factor turned out to be very influencing in girls. Remarkable was the change of Pb and Ca correlation positivity in group C children to correlation negativity in group E (ALAD, total proteins, CPL), or of correlation negativity to correlation positivity (A-1AT, TRF). The observed changes are discussed from the aspect of multifactorial action of Pb in the organism.

• MeSH
• alfa-1-antitrypsin analýza   MeSH
• ceruloplasmin analýza   MeSH
• dítě MeSH
• krevní proteiny analýza   MeSH
• lidé MeSH
• mladiství MeSH
• olovo krev   MeSH
• porfobilinogensynthasa krev   MeSH
• transferin analýza   MeSH
• vápník krev   MeSH
• věkové faktory MeSH
• znečištění ovzduší * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• alfa-1-antitrypsin MeSH
• ceruloplasmin MeSH
• krevní proteiny MeSH
• olovo MeSH
• porfobilinogensynthasa MeSH
• transferin MeSH
• vápník MeSH

A total of 138 workers of a motorcar transportation plant were examined to show a degree of lead damage. The analysis of obtained results was conducted from the two points of view: 1) according to employment time in plant; 2) according to work groups. The following laboratory examinations were carried out: delta-aminolevulin acid and coproporphyrin urinary excretion; determination of serous transaminase of glutaminoxalacetic acid and glutamin and piruvic acid, leucinaminopeptidase, whole protein, albumin-globulin coefficient, protein fractions (albumin alpha 1-, alpha 2-, beta 1-, beta 2, gamma) as well as of dehydratase activity of delta-aminolevulin acid in erythrocytes. In conformity with literary data an increased urinary excretion of delta-aminolevulin acid and of coproporphyrin to a different degree, as well as a decrease of dehydratase content of delta-aminolevulin acid in erythrocytes were detected. In the authors' view attention is to be drawn to a minor or greater extent to proportional increase of leucinaminopeptidase content however, in all the age groups and all the professional categories. The results of present examinations are considered by authors an important and sensitive parameter to evidence of lead damage.

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• časové faktory MeSH
• diferenciální diagnóza MeSH
• erytrocyty enzymologie   MeSH
• koproporfyriny moč   MeSH
• krevní proteiny analýza   MeSH
• kyselina aminolevulová moč   MeSH
• leucylaminopeptidasa krev   MeSH
• lidé MeSH
• otrava olovem diagnóza   MeSH
• porfobilinogensynthasa krev   MeSH
• sérové globuliny analýza   MeSH
• sérový albumin analýza   MeSH
• zaměstnání MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• alanintransaminasa MeSH
• aspartátaminotransferasy MeSH
• koproporfyriny MeSH
• krevní proteiny MeSH
• kyselina aminolevulová MeSH
• leucylaminopeptidasa MeSH
• porfobilinogensynthasa MeSH
• sérové globuliny MeSH
• sérový albumin MeSH

The changes of delta-aminolaevulinic acid dehydratase--the second enzyme of porphyrin synthesis--were studied and compared in the liver of mice and rats treated with griseofulvin. The results showed that griseofulvin increased the activity of delta-aminolaevulinic acid dehydratase in the liver of mice and rats treated by griseofulvin. No differences were found between mice and rats as to the effect of griseofulvin on the activity of delta-aminolaevulinic acid dehydratase. The influence of the administration of actinomycin D on the activity of delta-aminolaevulinic acid synthetase and dehydratase in the liver of mice and rats was studied at an early period of experimental porphyria induced by griseofulvin. It was found that the administration of actinomycin D blocked the observed effect of griseofulvin on the activity of both enzymes in the liver of mice and rats.

• MeSH
• 5-aminolevulátsynthetasa metabolismus   MeSH
• daktinomycin farmakologie   MeSH
• dehydratasy metabolismus   MeSH
• griseofulvin antagonisté a inhibitory   farmakologie   MeSH
• játra enzymologie   MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• porfobilinogensynthasa metabolismus   MeSH
• porfyrie chemicky indukované   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 5-aminolevulátsynthetasa MeSH
• daktinomycin MeSH
• dehydratasy MeSH
• griseofulvin MeSH
• porfobilinogensynthasa MeSH