Understanding the mechanisms of pollutant removal in Wastewater Treatment Plants (WWTPs) is crucial for controlling effluent quality efficiently. However, the numerous treatment units, operational factors, and the underlying interactions between these units and factors usually obfuscate the comprehensive and precise understanding of the processes. We have previously proposed a machine learning (ML) framework to uncover complex cause-and-effect relationships in WWTPs.
View Article and Find Full Text PDFDue to the intrinsic complexity of wastewater treatment plant (WWTP) processes, it is always challenging to respond promptly and appropriately to the dynamic process conditions in order to ensure the quality of the effluent, especially when operational cost is a major concern. Machine Learning (ML) methods have therefore been used to model WWTP processes in order to avoid various shortcomings of conventional mechanistic models. However, to the best of the authors' knowledge, no ML applications have focused on investigating how operational factors can affect effluent quality.
View Article and Find Full Text PDFThe attack of acute porphyria Based on in silico evidence of pharmacokinetic, pharmacodynamic, and physiologic properties, have approximately 1 300 medicinal drugs been assessed with regard to the specific risk to carriers of acute porphyria. The classifications have been published in booklet form, together with prophylactic advice to the carriers and suggestions for doctors in charge of their care. The risk-classifications rest on the behavior of the drug in an extended molecular model of the attack of acute porphyria.
View Article and Find Full Text PDFThe acute porphyrias are a group of disorders which result from inherited defects in the enzymes of the heme biosynthetic pathway. Affected patients are prone to potentially fatal acute attacks. These attacks are frequently precipitated by exposure to commonly used drugs.
View Article and Find Full Text PDFBr J Clin Pharmacol
November 2007
Aims: This paper addresses two common problems in the care of carriers of acute porphyria: the choice of safe drugs for pharmacotherapy and the strategy to apply when potentially unsafe drugs cannot be avoided.
Methods And Results: A technique is presented for prediction of risk that a certain drug may activate the disease in a gene carrier for acute porphyria. It is based on a model explaining the clinical manifestations as a result of the acute overloading of a deficient enzyme within the hepatic heme biosynthetic chain.
Porphyrias are uncommon inherited diseases of haem biosynthesis for which the diagnosis and treatment varies in individual countries. Despite the existence of guidelines recommended by porphyria experts concerning the diagnosis and management of the acute porphyrias, and of specialist centres in most European countries, many clinicians still do not apply these guidelines. The European Porphyia Initiative (EPI) network was formed in 2001 in order to compare experience among countries to attempt to develop a common approach to the management of the porphyrias, particularly concerning recommendation of safe and unsafe drugs, and to facilitate international collaborative clinical and biological research.
View Article and Find Full Text PDFIf I were living in Caucasus I would be writing fairy tales there Chekov, 1888 The question of the reasons for the extreme variation in morbidity among the gene carriers of acute porphyria and the great diversity of the precipitating factors are approached by the aid of a model of interacting genomic circuits. It is based on the current paradigm of the acute porphyric attack as a result of a toxic proximal overload of the enzyme-deficient heme-biosynthetic patway. Porphyrogenic influx of precursors is seen as a consequence of uncontrolled induction of its gate-keeping enzyme, ubiquitous 5-aminolevulinate synthase (ALAS1), due to attenuated post-translational control of the enzyme combined with activated gene transcription.
View Article and Find Full Text PDFIn a brief survey the work of Swedish porphyrinologists through time is presented, from the organic chemist Jakob Berzelius 1840 to the molecular biologists of today. The building up in Stockholm of a Swedish national competence centre for porphyria is touched upon and the emergence of a computerized national register on the porphyria gene carriers in the country described. Figures for the prevalences of the seven different forms of porphyria diagnosed in Sweden are given.
View Article and Find Full Text PDFThe properties of 9 delta-aminolevulinate dehydratase (ALAD) mutants from patients with ALAD porphyria (ADP) were examined by bacterial expression of their complementary DNAs and by enzymologic and immunologic assays. ALADs were expressed as glutathione-S-transferase (GST) fusion proteins in Escherichia coli and purified by glutathione-affinity column chromatography. The GST-ALAD fusion proteins were recognized by anti-ALAD antibodies and were enzymatically active as ALAD.
View Article and Find Full Text PDFAn extremely painful cutaneous condition with no or only slight visible skin changes, presenting in a child or an adult as an acute reaction to sun light, is probably a manifestation of the porphyrin metabolic disorder erythropoietic protoporphyria (EPP). The disease is the result of a genetically determined condition where a mutation in the gene for the final enzyme in the haem synthetic chain, ferrochelatase, results in impaired activity of the enzyme. In some predisposed individuals, the condition is accompanied by heavy accumulation of the substrate for the deficient enzyme, i.
View Article and Find Full Text PDFDeficiency of the fifth enzyme in haem synthesis, uroporphyrinogen decarboxylase (UPGD), may give rise to accumulation and excretion of poly-carboxylated porphyrins, as well as to clinical manifestations in the form of a phototoxic skin reaction and liver engagement leading to cirrhosis and hepatocellular cancer. The cutaneous reaction, presenting as skin fragility and blisters on areas exposed to sun--porphyria cutanea tarda (PCT)--develops only in individuals with a remaining hepatic UPGD activity less than 20% of normal. Experimental results and clinical observation give evidence that PCT is a multifactorial disease.
View Article and Find Full Text PDFScand J Clin Lab Invest
November 2000
The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric symptoms. Early diagnosis is of prime importance since it makes way for counselling with the aim to block the development of acute, as well as late, disease.
View Article and Find Full Text PDFThe biosynthesis of porphyrins is one of the most conserved parthways known, about the same sequence of reactions taking place in all species. By associating different metals, porphyrins give rise to the "pigments of life": chlorophyll, haem and cobalamin. The unique tetrapyrrolic structure enables it to function in an array of reactions as a single electron carrier and as a catalyst for redox reactions.
View Article and Find Full Text PDFThe possible interference of hexachlorobenzene and octachlorostyrene (i.e., thermal byproducts from hexachloroethane in aluminum degassing) with porphyrin metabolism was investigated in exposed workers.
View Article and Find Full Text PDFUgeskr Laeger
November 1998
Several drugs may induce or exacerbate symptoms in acute porphyria. This includes most psychotropic drugs, which makes the treatment of psychiatric symptoms in the porphyric patient difficult. A patient with a paranoid psychotic condition related to acute intermittent porphyria was treated with perphenazine.
View Article and Find Full Text PDFPorphyria cutanea tarda (PCT) is probably the most common of the porphyrias. The development of skin fragility and blisters are the symptoms that generally bring the patient to the notice of the dermatologist. During the past decade the disease has been recognised as being of heterogeneous aetiology, and a pathogenetic classification has been proposed.
View Article and Find Full Text PDFErythropoietic protoporphyria (EPP) presents clinically as a painful skin reaction to sun-light exposure. The profoundly disabling psychosocial consequences of the disease often go unnoticed by the physician, and the need to monitor the patient for hepatic complications is not generally recognised. The article describes the clinical and biochemical course in a 51-year-old man with EPP, who within a few days developed signs of acute hepatic failure.
View Article and Find Full Text PDFRecent mapping of acute intermittent porphyria (AIP) in Sweden has confirmed its very high prevalence in northern districts, though about fifty per cent of the gene carriers are to be found in the central and southern parts of the country. More than eighteen different AIP mutations are currently recognised in the Swedish kindreds. One mutations, evidently originating in northern Sweden, is predominant.
View Article and Find Full Text PDFThe porphyrias, uncommon conditions often eluding diagnosis, extremely susceptible to inappropriate treatment and associated with severe late manifestations, are representative of the small groups of scarce and complex diseases that are difficult to manage without specialised resources. A network of offices with diagnostic and consultative support from a national specialist centre is probably the most cost effective way of meeting the patients' demands in terms of highly specialised medical experience coupled with close contact and continuity This approach, adopted by the Swedish Porphyria Centre, is based on well structured and regularly updated programmes for the management of porphyria patients.
View Article and Find Full Text PDFThere are no reports on effects of large blood losses in acute hepatic porphyria. In the present study we report the experiences of repeated large therapeutic phlebotomies in a patients with porphyria cutanea tarda coexisting with variegate porphyria. Neither a series of 12 phlebotomies, 300 mL each, resulting in a 17% decrease in blood haemoglobin, nor a single 400 mL phlebotomy activated the acute porphyric condition.
View Article and Find Full Text PDFA total of 12 mutations associated with acute intermittent porphyria (AIP) have been detected in the porphobilinogen deaminase gene in Swedish AIP families. Three of them are newly discovered and unique to the Swedish population: a splice mutation in intron 6 (int6+1), a missense mutation in exon 11 (Gly216Asp) and a TG deletion in exon 14.
View Article and Find Full Text PDFEur J Clin Chem Clin Biochem
June 1997
In order to elucidate the question of free radical involvement in acute porphyric crisis, antioxidants were administered to two acute intermittent porphyria patients with long-standing recurrent attacks. Clinical condition and urinary excretion of porphyrins and porphyrin precursors were monitored before, during and after an eight week therapy with daily doses of vitamin E, beta-carotene, ascorbic acid, selenium, vitamin Q, acetylcysteine, mannitol and carnitine. Blood cell trace element profiles were followed.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
February 1997
The significantly increased concentrations of granulocyte manganese in subjects with AIP may be an indication of overexpression of manganese-associated enzymes. In this study we present further observations related to this phenomenon and speculate that this may provide a rational basis for hypotheses attempting to explain the pathogenesis of the acute attack of porphyria. Such hypotheses are advanced with regard to pyruvate carboxylase, mitochondrial superoxide dismutase and glutamine synthetase, three manganese-dependent enzymes associated with either ALA-generating or ALA-dependent processes.
View Article and Find Full Text PDFWe have detected four different mutations in the porphobilinogen deaminase (PBGD) gene in acute intermittent porphyria (AIP) families from England, Norway, and Sweden. A splicing mutation in the first position of intron 8 (Int8 + 1) was found in a family from England and a missense mutation in exon 12 (Glu250) was detected in a Norwegian family. Two mutations were identified in Swedish families, one splicing mutation in the first position of intron 3 (Int3 + 1) and one missense mutation in exon 8 (Pro119).
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