LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 81

Search options

  1. Article: First decade anniversary of the United Kingdom National Alkaptonuria Centre.

    Khedr, Milad / Sireau, Nick / Bou-Gharios, George / Gallagher, Jim A / Ranganath, Lakshminarayan R

    JIMD reports

    2023  Volume 64, Issue 2, Page(s) 212–213

    Language English
    Publishing date 2023-01-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2672872-2
    ISSN 2192-8312 ; 2192-8304
    ISSN (online) 2192-8312
    ISSN 2192-8304
    DOI 10.1002/jmd2.12340
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article: Analysis of the Phenotype Differences in Siblings with Alkaptonuria.

    Zatkova, Andrea / Olsson, Birgitta / Ranganath, Lakshminarayan R / Imrich, Richard

    Metabolites

    2022  Volume 12, Issue 10

    Abstract: Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by mutations within a gene coding for homogentisate 1,2-dioxygenase (HGD). To date, 251 different variants of this gene have been reported. The metabolic disorder in AKU leads to the ... ...

    Abstract Alkaptonuria (AKU) is a rare autosomal recessive disorder caused by mutations within a gene coding for homogentisate 1,2-dioxygenase (HGD). To date, 251 different variants of this gene have been reported. The metabolic disorder in AKU leads to the accumulation of homogentisic acid (HGA), resulting in ochronosis (pigmentation of the connective tissues) and severe ochronotic spondylo-arthropathy, which usually manifests in the mid-thirties. An earlier genotype−phenotype correlation study showed no differences in serum HGA levels, absolute urinary excretion of HGA, or in the clinical symptoms between patients carrying HGD variants leading to 1% or >30% residual HGD activity. Still, as reported previously, the variance of the excretion of the HGA was smaller within affected siblings that share a common genotype. The present study is the first ever to systematically analyze the baseline clinical data of 24 AKU sibling pairs/groups collected in the SONIA 2 (Suitability Of Nitisinone In Alkaptonuria 2) study to evaluate phenotypical differences between patients carrying the same HGD genetic variants. We show that even between siblings there was considerable variability in the disease severity. This indicates that some other yet unidentified genetic, biomechanical, or environmental modifying factors may contribute to accelerated pigmentation and connective tissue damage observed in some patients.
    Language English
    Publishing date 2022-10-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo12100990
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Development of an Effective Therapy for Alkaptonuria - Lessons for Osteoarthritis.

    Gallagher, James A / Dillon, Jane P / Ranganath, Lakshminarayan R

    Rheumatology and immunology research

    2021  Volume 2, Issue 2, Page(s) 79–85

    Abstract: Osteoarthritis (OA) is one of the major causes of disability and pain worldwide, yet despite a massive international research effort, no effective disease-modifying drugs have been identified to date. In this review, we put forward the proposition that ... ...

    Abstract Osteoarthritis (OA) is one of the major causes of disability and pain worldwide, yet despite a massive international research effort, no effective disease-modifying drugs have been identified to date. In this review, we put forward the proposition that greater focus on rarer forms of OA could lead to a better understanding of the pathogenesis of more common OA. We have investigated the severe osteoarthropathy of the ultra-rare disease alkaptonuria (AKU). In addition to the progress made in finding a treatment for AKU, our research has revealed important lessons for more common OA, including the identification of high-density mineralized protrusions (HDMPs), new pathoanatomical structures which may play an important role in joint destruction and pain in AKU and in OA. AKU is an inherited disorder of tyrosine metabolism, caused by genetic lack of the enzyme homogentisate 1,2 dioxygenase (HGD), which leads to failure to breakdown homogentisic acid (HGA). While most HGA is excreted over time, some of it is deposited as a pigment in connective tissues, a process described as ochronosis. Ochronotic pigment alters the mechanical properties of tissues, leading to inevitable joint destruction and frequently to cardiac valve disease. Until recently, there was no effective therapy for AKU, but preclinical studies demonstrated that upstream inhibition of tyrosine metabolism by nitisinone, a drug previously used in hereditary tyrosinaemia 1 (HT1), completely prevented ochronosis in AKU mice. This was followed by successful clinical trials which have resulted in nitisinone being approved for therapy of AKU by the European Medicines Agency, making AKU the only cause of OA for which there is an effective therapy to date. Study of other rare causes of OA should be a higher priority for researchers and funders to ensure further advances in understanding and eventual therapy of OA.
    Language English
    Publishing date 2021-09-28
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 2719-4523
    ISSN (online) 2719-4523
    DOI 10.2478/rir-2021-0011
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article: Long-term low dose nitisinone therapy in adults with alkaptonuria shows no cognitive decline or increased severity of depression.

    Davison, Andrew S / Hughes, Gin / Harrold, Joanne A / Clarke, Pam / Griffin, Rebecca / Ranganath, Lakshminarayan R

    JIMD reports

    2022  Volume 63, Issue 3, Page(s) 221–230

    Abstract: Little is documented on whether nitisinone-induced hypertyrosinaemia alters cognitive functioning or leads to worsening depression in alkaptonuria (AKU). Wechsler Adult Intelligence Scale-IV (WAIS-IV) and Beck Depression Inventory-II (BDI-II) assessments ...

    Abstract Little is documented on whether nitisinone-induced hypertyrosinaemia alters cognitive functioning or leads to worsening depression in alkaptonuria (AKU). Wechsler Adult Intelligence Scale-IV (WAIS-IV) and Beck Depression Inventory-II (BDI-II) assessments were performed before and annually following treatment with nitisinone 2 mg daily to assess the impact on cognitive functioning and severity of depression. Serum tyrosine concentrations were also measured annually.
    Language English
    Publishing date 2022-03-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2672872-2
    ISSN 2192-8312 ; 2192-8304
    ISSN (online) 2192-8312
    ISSN 2192-8304
    DOI 10.1002/jmd2.12272
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Characterizing the alkaptonuria joint and spine phenotype and assessing the effect of homogentisic acid lowering therapy in a large cohort of 87 patients.

    Ranganath, Lakshminarayan R / Khedr, Milad / Vinjamuri, Sobhan / Gallagher, James A

    Journal of inherited metabolic disease

    2021  Volume 44, Issue 3, Page(s) 666–676

    Abstract: A large alkaptonuria (AKU) cohort was studied to better characterize the poorly understood spondyloarthropathy of rare disease AKU. Eighty-seven patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Seven only attended once. ... ...

    Abstract A large alkaptonuria (AKU) cohort was studied to better characterize the poorly understood spondyloarthropathy of rare disease AKU. Eighty-seven patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Seven only attended once. Fifty-seven attended more than once and received nitisinone 2 mg daily. Twenty-three attended at least twice without receiving nitisinone. Assessments included questionnaire analysis,
    MeSH term(s) Aged ; Alkaptonuria/drug therapy ; Alkaptonuria/metabolism ; Cohort Studies ; Cyclohexanones/administration & dosage ; Female ; Homogentisic Acid/metabolism ; Humans ; Joints/diagnostic imaging ; Joints/pathology ; Linear Models ; Male ; Middle Aged ; Nitrobenzoates/administration & dosage ; Ochronosis/drug therapy ; Ochronosis/metabolism ; Phenotype ; Positron Emission Tomography Computed Tomography ; Severity of Illness Index ; Spine/diagnostic imaging ; Spine/pathology ; United Kingdom
    Chemical Substances Cyclohexanones ; Nitrobenzoates ; nitisinone (K5BN214699) ; Homogentisic Acid (NP8UE6VF08)
    Language English
    Publishing date 2021-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 438341-2
    ISSN 1573-2665 ; 0141-8955
    ISSN (online) 1573-2665
    ISSN 0141-8955
    DOI 10.1002/jimd.12363
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1508: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Evaluation of Homogentisic Acid, a Prospective Antibacterial Agent Highlighted by the Suitability of Nitisinone in Alkaptonuria 2 (SONIA 2) Clinical Trial.

    Ooi, Nicola / Cooper, Ian R / Norman, Brendan / Gallagher, James A / Sireau, Nick / Bou-Gharios, George / Ranganath, Lakshminarayan R / Savage, Victoria J

    Cells

    2023  Volume 12, Issue 13

    Abstract: Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic ... ...

    Abstract Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic development programs and should be actively sought out. Evaluation of homogentisic acid (HGA), an intermediate in the tyrosine degradation pathway, showed that the compound had innate activity against Gram-positive and Gram-negative bacteria, which was lost following conversion into the degradation product benzoquinone acetic acid (BQA). Anti-staphylococcal activity of HGA can be attributed to effects on bacterial membranes. Despite an absence of haemolytic activity, the compound was cytotoxic to human HepG2 cells. We conclude that the antibacterial activity and in vitro safety profile of HGA render it more suitable for use as a topical agent or for inclusion in a small-molecule medicinal chemistry program.
    MeSH term(s) Humans ; Alkaptonuria/drug therapy ; Alkaptonuria/metabolism ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Gram-Negative Bacteria/metabolism ; Gram-Positive Bacteria ; Homogentisic Acid/metabolism ; Prospective Studies
    Chemical Substances Anti-Bacterial Agents ; Homogentisic Acid (NP8UE6VF08) ; nitisinone (K5BN214699)
    Language English
    Publishing date 2023-06-21
    Publishing country Switzerland
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12131683
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Alkaptonuria.

    Bernardini, Giulia / Braconi, Daniela / Zatkova, Andrea / Sireau, Nick / Kujawa, Mariusz J / Introne, Wendy J / Spiga, Ottavia / Geminiani, Michela / Gallagher, James A / Ranganath, Lakshminarayan R / Santucci, Annalisa

    Nature reviews. Disease primers

    2024  Volume 10, Issue 1, Page(s) 16

    Abstract: Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease ... ...

    Abstract Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients' quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies.
    MeSH term(s) Male ; Humans ; Female ; Alkaptonuria/complications ; Alkaptonuria/diagnosis ; Alkaptonuria/therapy ; Quality of Life ; Ochronosis/complications ; Ochronosis/diagnosis ; Kidney/metabolism ; Homogentisic Acid/metabolism
    Chemical Substances Homogentisic Acid (NP8UE6VF08)
    Language English
    Publishing date 2024-03-07
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2056-676X
    ISSN (online) 2056-676X
    DOI 10.1038/s41572-024-00498-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article: Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index.

    Cant, Harriet E O / Chatzidaki, Iro / Olsson, Birgitta / Rudebeck, Mattias / Arnoux, Jean-Baptiste / Imrich, Richard / Eddowes, Lucy A / Ranganath, Lakshminarayan R

    JIMD reports

    2022  Volume 63, Issue 4, Page(s) 361–370

    Abstract: Alkaptonuria (AKU) is a rare genetic disorder where oxidised homogentisic acid accumulates in connective tissues, leading to multisystem disease. The clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) is a composite score that assesses the ... ...

    Abstract Alkaptonuria (AKU) is a rare genetic disorder where oxidised homogentisic acid accumulates in connective tissues, leading to multisystem disease. The clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) is a composite score that assesses the extent of AKU disease. However, some components assess similar disease features, are difficult to measure reliably or cannot be measured in resource-limited environments. cAKUSSI data from the 4-year SONIA 2 randomised controlled trial, which investigated nitisinone treatment in adults with AKU, were analysed (
    Language English
    Publishing date 2022-05-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2672872-2
    ISSN 2192-8312 ; 2192-8304
    ISSN (online) 2192-8312
    ISSN 2192-8304
    DOI 10.1002/jmd2.12290
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Characterising the arthroplasty in spondyloarthropathy in a large cohort of eighty-seven patients with alkaptonuria.

    Ranganath, Lakshminarayan R / Gallagher, James A / Davidson, John / Vinjamuri, Sobhan

    Journal of inherited metabolic disease

    2020  Volume 44, Issue 3, Page(s) 656–665

    Abstract: Arthroplasty in the spondyloarthropathy (SPOND) of alkaptonuria (AKU) in incompletely characterised. The aim was to improve the understanding of arthroplasty in AKU through a study of patients attending the National Alkaptonuria Centre (NAC). Eighty- ... ...

    Abstract Arthroplasty in the spondyloarthropathy (SPOND) of alkaptonuria (AKU) in incompletely characterised. The aim was to improve the understanding of arthroplasty in AKU through a study of patients attending the National Alkaptonuria Centre (NAC). Eighty-seven patients attended the NAC between 2007 and 2020. Seven only attended once. Fifty-seven attended more than once and received nitisinone 2 mg daily. Twenty-three attended at least twice without receiving nitisinone. Assessments including questionnaire analysis eliciting details of arthroplasty and other surgical treatments for SPOND,
    MeSH term(s) Aged ; Alkaptonuria/complications ; Alkaptonuria/drug therapy ; Arthroplasty/statistics & numerical data ; Cohort Studies ; Cyclohexanones/administration & dosage ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Nitrobenzoates/administration & dosage ; Ochronosis/complications ; Ochronosis/drug therapy ; Positron Emission Tomography Computed Tomography ; Spondylarthropathies/diagnostic imaging ; Spondylarthropathies/surgery ; United Kingdom
    Chemical Substances Cyclohexanones ; Nitrobenzoates ; nitisinone (K5BN214699)
    Language English
    Publishing date 2020-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 438341-2
    ISSN 1573-2665 ; 0141-8955
    ISSN (online) 1573-2665
    ISSN 0141-8955
    DOI 10.1002/jimd.12340
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1508: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Ochronotic pigmentation is caused by homogentisic acid and is the key event in alkaptonuria leading to the destructive consequences of the disease-A review.

    Ranganath, Lakshminarayan R / Norman, Brendan P / Gallagher, James A

    Journal of inherited metabolic disease

    2019  Volume 42, Issue 5, Page(s) 776–792

    Abstract: Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)-derived pigment in tissues altering the properties of these tissues, leading to their failure. ...

    Abstract Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)-derived pigment in tissues altering the properties of these tissues, leading to their failure. Some tissues like cartilage are more easily affected by ochronosis while others such as the liver and brain are unaffected for reasons that are still not understood. In vitro and mouse models of ochronosis have confirmed the dose relationships between HGA and ochronosis and also their modulation by p-hydroxyphenylpyruvate dioxygenase inhibition. Ochronosis cannot be fully reversed and is a key factor in influencing treatment decisions. Earlier detection of ochronosis preferably by noninvasive means is desirable. A cause-effect relationship between HGA and ochronosis is discussed. The similarity in AKU and familial hypercholesterolaemia is explored and lessons learnt. More research is needed to more fully understand the crucial nature of ochronosis.
    MeSH term(s) Alkaptonuria/metabolism ; Alkaptonuria/pathology ; Animals ; Cartilage/metabolism ; Cartilage/pathology ; Chondrocytes/cytology ; Chondrocytes/metabolism ; Homogentisic Acid/metabolism ; Humans ; Mice ; Ochronosis/pathology ; Oxidation-Reduction ; Pigmentation
    Chemical Substances Homogentisic Acid (NP8UE6VF08)
    Language English
    Publishing date 2019-08-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 438341-2
    ISSN 1573-2665 ; 0141-8955
    ISSN (online) 1573-2665
    ISSN 0141-8955
    DOI 10.1002/jimd.12152
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1508: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top