Retrospective epidemyological studies evidence that infant diseases leave survivors with an increased susceptibility to cardiovascular diseases in later life. At the same time, the mechanisms of this link remain poorly understood. Based on medical statistics reporting that infectious gastroenteritis is the most common cause of maladies in babies, infants and children, we analysed the effects of moderate cryptosporidial gastroenteritis on the heart and ventricular cardiomyocyte remodelling in rats of the first month of life. The disease was challenged by a worldwide human protozoic pathogen Cryptosporidium parvum (Apicomplexa, Sporozoa). The main symptoms manifested in the growth retardation moderate diarrhea. Using real-time PCR, cytophotometry, confocal microscopy and image analysis, we indicated that cryptosporidiosis was associated, with the atrophy heart and the elongation, narrowing, protein content decrease and hyperpolyploidization of cardiomyocytes and the moderate overexpression of hypoxia inducible factor 1alpha (HIF-1alpha) mRNA. Cardiomyocyte shape remodeling and heart atrophy presented in all age groups. The severity of these changes, hovewer, declined gradually from younger to older groups. In contrast, hyperpolyploidization and HIF-1alpha mRNA overexpression were registered mainly among animals aged between 6 and 13 days, and were barely detected and non-significant in older age groups. In the rat the time period covering 6-13 days after birth is known to coincide with the intensive cardiomyocyte polyploidization and the switch from proliferation to hypertrophy. Thus, our data indicate that neonatal cryptosporidiosis may be potential cardiovascular diseases risk factor and that one of the critical time windows for the growing heart covers the time period when cardiomyocyte undergo polyploidization.
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Front Cell Infect Microbiol
December 2024
Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
Introduction: is the most prevalent enteric protozoan parasite causing infectious diarrhea in neonatal calves worldwide with a direct negative impact on their health and welfare. This study utilized next-generation sequencing (NGS) to deepen our understanding of intestinal epithelial barriers and transport mechanisms in the pathophysiology of infectious diarrhea in neonatal calves, which could potentially unveil novel solutions for treatment.
Methods: At day 1 of life, male Holstein-Friesian calves were either orally infected (n = 5) or not (control group, n = 5) with oocysts (in-house strain LE-01-Cp-15).
Eur J Pharm Biopharm
December 2024
Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address:
Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro.
View Article and Find Full Text PDFJDS Commun
November 2024
Division of Clinical Veterinary Medicine, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, 080-8555 Japan.
Cryptosporidiosis is a major cause of diarrhea and is associated with high morbidity in calves. Changes in the gut microbiota exacerbate diarrhea caused by infection in neonatal and weaned calves. However, information on the gut microbiota of neonatal calves with infection is scarce, and research into the microbiome of calves is essential for developing preventive and therapeutic interventions.
View Article and Find Full Text PDFVet World
September 2024
Department of Parasitology and Animal Diseases, National Research Centre, Dokki-Giza, Egypt.
Background And Aim: Cryptosporidiosis is a major waterborne disease affecting ruminants and humans worldwide. It causes diarrhea and neonatal mortality in buffalo calves, and watery diarrhea and mortality in children and immunodeficient patients. This study aimed to investigate the efficacy of methanolic extract in treatment of infection in comparison with nitazoxanide (NZX) (a Food and Drug Administration-approved drug control) in immunosuppressed and immunocompetent mice.
View Article and Find Full Text PDFNat Microbiol
November 2024
Global Health, Biomedical Research, Novartis, Emeryville, CA, USA.
Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site.
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