Search Results (52)

Iron is essential for life, but its safe use by the body depends on it being kept within tightly controlled compartments. When this compartmentalisation is disrupted—through haemolysis, saturation of scavenger proteins, or dysregulation of the hepcidin–ferroportin axis—damaging iron species accumulate in the circulation and within vascular cells, with potentially serious consequences for endothelial function. This review explores the mechanisms by which iron dysregulation compromises vascular endothelial cell biology across a range of disease states, including haemolytic anaemias, atherosclerosis, cerebrovascular disease, extracorporeal circulatory support, and iatrogenic iron loading. Common pathological themes emerge: depletion of nitric oxide bioavailability, oxidative stress, endothelial activation, and in chronic settings, vascular remodelling. The review subsequently focuses in depth on the pulmonary vasculature, where dysregulated iron compartmentalisation has emerged as a key contributor to the pathogenesis of pulmonary hypertension. Here, iron-driven mitochondrial dysfunction, smooth muscle cell proliferation, and iron-dependent lipid peroxidation via ferroptosis are discussed as mechanistic drivers of pulmonary vascular remodelling. The therapeutic implications of targeting iron handling in pulmonary hypertension are considered, including modulation of the hepcidin–ferroportin axis. Together, the evidence presented highlights disordered iron compartmentalisation as a unifying pathological thread across vascular disease and a compelling target for intervention. Full article

Background/Objectives: The aquaculture industry represents a fundamental food sector. One of the main limiting factors for this sector is related to bacterial diseases, for which antibiotics have been widely used worldwide for decades. In recent years, a more conscious approach to the use of antimicrobials within the framework of the One Health approach has increased the need for alternatives capable of helping with disease management while avoiding the onset of antimicrobial resistance phenomena. Antimicrobial peptides, which have a broad spectrum of action against pathogens, are a promising solution. Methods: In this work, we investigated the capability of three peptides (Trematocine, Chionodracine, and Cnd-m3) isolated from Antarctic fish to target bacterial and viral pathogens affecting aquaculture. Successively, we investigated their cytotoxicity versus a continuous embryonic cell line (DLEC) derived from European sea bass and their haemolytic activity against fish erythrocytes. Moreover, we evaluated their immunomodulatory effect. Results: Regarding antibacterial properties, Cnd-m3 was identified as the best peptide, demonstrating good bactericidal and bacteriostatic activity against various bacterial strains, including Lactococcus garvieae. Concerning this bacterium, ANS permeability assays showed that the Cnd-m3 peptide has a great ability to interact with its outer membrane, while TEM analysis revealed that the peptide, after destabilization of the cell membrane, interacts with nucleic structures. Considering the antiviral activity, Trematocine was effective against two tested pathogenic enveloped viruses. Moreover, the toxicity of Trematocine and Cnd-m3 was evaluated by investigating their cytotoxicity against a cell line derived from Dicentrarchus labrax and haemolysis against sea bass erythrocytes. Both revealed good selectivity towards pathogens at the lowest concentration. Finally, Cnd-m3 manifested light in vitro immunomodulatory properties. Conclusions: Overall, these data provide a solid basis for future studies assessing the potential applications of two of the tested peptides in aquaculture. Full article

Introduction: Haemolytic Escherichia coli (E. coli) is commonly associated with enteric disease in pigs and is frequently used as a phenotypic marker for enterotoxigenic E. coli (ETEC). This study aimed to characterise the resistance and virulence profiles of haemolytic E. coli isolated from Colombian pig farms. Methods: A total of 367 faecal samples from sows and pigs across all production stages were collected and analysed for the presence of haemolytic E. coli. Resistance and virulence genes associated with ETEC was detected by multiplex PCR, and antimicrobial susceptibility profiles were determined using broth microdilution and disc diffusion. Results: Haemolytic E. coli were identified in 40.3% of samples (n = 148 non-duplicate isolates), with the highest prevalence observed in growing piglets (47.1%). ETEC occurred in 5.4% of isolates. All isolates exhibited resistance to at least three antimicrobial classes (MDR), with high levels of resistance to tetracycline (98.0%), neomycin (97.3%), chloramphenicol (95.9%), sulfamethoxazole (93.9%), trimethoprim (91.9%), ampicillin (91.9%), nalidixic acid (82.4%), and ciprofloxacin (79.7%). Colistin resistance was observed in 5.4% of isolates, mediated by mcr1 or mcr3, while cefotaxime resistance (8.8%) was extensively associated with blaCTX-M. Conclusions: These findings reveal a concerning burden of MDR E. coli in Colombia’s pig-producing regions and indicate that haemolysis alone is a poor indicator of ETEC. Integrating farm-level antimicrobial use data with genomic analyses will be essential to identify drivers of AMR and guide effective stewardship in the Colombian pig industry. Full article

Implementation of molecular detection methodology of Shiga toxin-producing Escherichia coli (STEC) in Danish patients began in 1997. Since then, changes in molecular detection methods and diagnostic criteria have led to the present situation, in which almost all diarrhoeal stool specimens are examined for STEC. Whole genome sequencing (WGS) of STEC isolates referred to the national reference laboratory has increased the detailed characterisation, and revealed a large spectrum, of STEC types, including cross-over pathotypes typically associated with extraintestinal disease or traveller’s diarrhoea. Association of subtype stx2a (and stx2d) with the risk of developing haemolytic uraemic syndrome (HUS) was confirmed. These changes have resulted in an increase in the number of diagnosed STEC cases from 31 cases in 1997 to 1432 in 2023. Similar increases in Europe have also been recorded. Culture of STEC is, on the other hand, declining, which poses a challenge to the identification of multiple STEC infections and outbreaks. Syndromic (PCR) test panels have also resulted in an increase in the detection of multiple microorganisms. Double or triple infections have increased the role of clinical microbiologists in interpreting and assessing the significance of diagnostic results and have also increased the need for high-quality curation of surveillance data. Full article

Background and Clinical Significance: Triosephosphate isomerase (TPI) deficiency is a rare autosomal recessive metabolic disorder caused by a pathogenic variant in the TPI1 gene. It is characterised by chronic haemolytic anaemia, progressive neuromuscular dysfunction, and reduced life expectancy. Patients typically present with symptoms in the first few months of life, including muscle weakness, ataxia, and recurrent respiratory infections. Diagnosis is confirmed by genetic testing, and management is generally symptomatic as no treatment is available. Case Presentation: We describe the case of an infant diagnosed with TPI deficiency in the context of haemolytic anaemia with progressive neurological deterioration and respiratory failure. Conclusions: This case illustrates the complexity of the disease and highlights the importance of early diagnosis and contributes to the limited literature by providing a detailed clinical description and highlighting the diagnostic challenges associated with this condition. Beyond its clinical relevance, this report emphasises the potential role of personalised medicine in the management of TPI deficiency. Early identification of specific genotypes may inform prognosis and guide individualised supportive strategies. As knowledge of the molecular underpinnings of TPI deficiency expands, opportunities may emerge for targeted therapeutic approaches tailored to patient-specific characteristics. Full article

Background/Objectives: The overuse and misuse of antibiotics has contributed significatively to the growing problem of the emergence and spread of antibiotic resistance genes among bacteria, posing a serious global challenge to the treatment of bacterial infectious diseases. For these reasons, there is a current and growing interest in the development of effective alternative or complementary strategies to antibiotic therapy for the prevention of fish diseases, which are mainly based on the use of probiotics—in particular, those belonging to the Lactic Acid Bacteria (LAB) group. In this context, the aim of the present study was to characterise, evaluate the genetic diversity and assess the safety of candidate probiotic LAB strains for aquaculture isolated from faeces and intestines of European hakes (Merluccius merluccius, L.) caught in the Northeast Atlantic Ocean (Ireland). Methods: The direct antimicrobial activity of the LAB isolates was tested by the Stab-On-Agar method against key ichthyopathogens. Subsequently, their taxonomic classification and genetic diversity were determined by 16SrDNA sequencing and Enterobacterial Repetitive Intergenic Consensus-PCR (ERIC-PCR), respectively. To ensure the in vitro safety of the LAB isolates, their biofilm-forming ability was assessed by a microtiter plate assay; their sensitivity to major antibiotics used in aquaculture, human and veterinary medicine by a broth microdilution method and their haemolytic and gelatinase activity by microbiological assays. Results: All LAB isolates were biofilm producers and susceptible to chloramphenicol, oxytetracycline, flumequine and amoxicillin. A total of 30 isolates (85.7%) were resistant to at least one of the tested antibiotics. None of the 35 LAB isolates showed haemolytic or proteolytic activity. Conclusions: Among the isolated strains, five LAB strains exhibiting the highest antimicrobial activity against aquaculture-relevant ichthyopathogens, taxonomically identified as Streptococcus salivarius, Enterococcus avium and Latilactobacillus sakei, were selected for further characterisation as potential probiotic candidates to promote sustainable aquaculture. To our knowledge, this is the first study to report that hake intestines and faeces represent viable ecological niches for the isolation of LAB strains with antimicrobial activity. Full article

The ever-growing global demand for animal protein forces the aquaculture industry to expand at a pace which imposes significant challenges in maintaining sustainable practices. This study aimed to investigate the efficacy of an organic acid mixture (Aq) in mitigating Lactococcus garvieae (L. garvieae) virulence through its effects on bacterial virulence (EPS production, biofilm, and haemolytic factors) and host pathogenicity, including its adherence to CHSE-214 cells, haemolysis, and proinflammatory responses. Our findings reveal that Aq significantly inhibits L. garvieae growth at a 0.125% concentration, suppresses EPS-related gene expression, reduces biofilm formation, and reduces cytotoxicity in fish epithelial cells (CHSE-214). Moreover, Aq decreased haemolysing gene expression (hly1, hly2 and hly3) and attenuated red blood cell haemolysis, a hallmark of L. garvieae pathogenicity. Lastly, Aq was demonstrated to induce modulation in the host immune responses, lowering IL-1β and IL-8 expression, which are critical mediators of inflammation and pathogen recruitment. Therefore, we conclude that the main mechanism of action of Aq involves inhibiting L. garvieae adhesion to epithelial cells, reducing EPS production, and downregulating key virulence-associated genes (e.g., hly1, hly2, and hly3). After preventing L. garvieae adherence and suppressing proinflammatory cytokine expression (IL-1β and IL-8), Aq disrupts the pathogen’s ability to breach epithelial barriers and induce red blood cell lysis, thereby mitigating its virulence and pathogenicity. Our results emphasised the potential of Aq as an alternative non-antibiotic intervention for controlling piscine lactococcosis, advancing our understanding of L. garvieae pathogenesis and providing the foundation for the future integration of environmentally friendly antimicrobials into aquaculture disease management. Full article

Thrombotic microangiopathy (TMA) is a category of diseases consisting of thrombocytopenia, microangiopathic haemolytic anaemia, and widespread occlusive microvascular thrombosis. We report two cases of a thrombotic microangiopathic syndrome associated with non-invasive mucinous cysts and mucinous adenocarcinoma. TMA was treated in both cases by surgical removal of the tumours. We hypothesise that mucin secretion in the case of non-invasive mucinous cysts and paraneoplastic secretion of antibodies in the case of mucinous adenocarcinomas are the causes of endothelial damage with thrombocytopenia and microangiopathic haemolytic anaemia. Finally, patients with TMA who exhibit unusual clinical characteristics or weak responses to plasma exchange should be examined for an underlying tumour. Tumour treatment is the preferred therapy for tumour-associated TMA. Full article

Introduction: The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a rare condition caused by an immune response associated with over-reactivity of the immune system, triggered by adjuvants. The most common adjuvants are aluminium salts but can also be bioimplants or infectious agents. It may lead to the development of various autoimmunologic diseases. Case Report: In the following article, we present the case of a 26-year-old woman who developed SLE likely induced by ASIA syndrome after the aesthetic medicine procedures. The patient was admitted because of arthralgia and fever. She also presented with a butterfly-shaped erythema on her face and erythematous and infiltrative skin lesions on the posterior surface of the thighs and buttocks. We performed numerous diagnostic tests, including laboratory tests, immunological tests, imaging diagnostics such as chest X-ray and USG of the abdomen and joints, and the biopsy of the skin lesion on the left thigh. The results of the diagnostic process led us to diagnose SLE. The patient fulfilled the ACR/EULAR 2019 classification criteria of the SLE. Laboratory results also led to the diagnosis of autoimmune haemolytic anaemia. Due to exposure to numerous adjuvants like tattoo ink, hyaluronic acid, and piercing and the development of the delayed inflammatory reaction (DIR) to hyaluronic acid (HAF), the patient also fulfilled the criteria of ASIA. In the treatment process we applied antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, hydroxychloroquine, and cyclosporine. The treatment resulted in an improvement in the general condition, resolution of swelling and joint pain, and improvement in skin lesions. Conclusions: ASIA syndrome after bioimplantation is still underdiagnosed, probably due to ignorance or diagnostic difficulties, as symptoms are uncharacteristic and there is no immunological marker for this syndrome. In addition, as in the presented case, it can develop several years after the procedure, and it is difficult for both patient and physician to become aware of the connection. Early diagnosis requires a multidisciplinary approach and may require immunosuppressive treatment in specific cases. Full article

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH, and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassaemia and 14.3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization were included in the study. The patients were divided into three groups according to the PH haemodynamic definition and overall diagnostic approach: 42.9% had precapillary PH (pulmonary arterial hypertension—PAH group), 25% had post-capillary PH, and 32.1% had chronic thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics were recorded. PAH-specific drug therapy received 82.1% of patients, and balloon pulmonary angioplasty (BPA) was performed in six patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for the PAH group. Patients who underwent BPA had improved pulmonary haemodynamics. The median survival time was 162 months, and the survival rate was 1 year—100%; 2, 3, 4, 5, and 6 years—96%; 9 years—90%; and 13 years—78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlighted the importance of a correct predominant diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies; however, the management should be offered in expert PH centres under individualized approaches for patients. Full article

Diabetes prevalence continues to increase worldwide, which has led to a rising incidence of diabetes-related foot infections (DFIs). There is significant local variation in the microbiology of DFIs, and Pseudomonas spp. is suggested to be more prevalent in subtropical climates. The aim of this study was to investigate the local microbiological findings in patients admitted to the hospital with DFIs. This retrospective study analysed data from all adult patients diagnosed with diabetes and admitted to the hospital for the treatment of a DFI between 1 January 2021 and 31 December 2022. Both superficial wound swabs and tissue cultures were included. The Infectious Diseases Society of America classification system was used to categorise the severity of the DFI. Patient characteristics and demographics were analysed using descriptive statistics. One hundred fifty-one episodes of care were included. Most of the DFIs were classified as moderate infections 101/151 (67%). The most commonly isolated microorganism was Staphylococcus aureus (33%) followed by normal skin flora (11%) and β-haemolytic streptococci (7%). P. aeruginosa was isolated more commonly in those with chronic DFIs (10%) compared to those with acute DFIs (2%). Despite the frequent identification of S. aureus, 83% of patients received an antipseudomonal antibiotic. The introduction of multidisciplinary DFI rounds should be considered. Full article

Insect farming is gaining attention as a promising area for exploring probiotic bacteria, which can benefit both insect health and various industries. Silkworm farming is a key industry in Thailand; however, challenges such as disease susceptibility and optimising growth require innovative solutions for sustainable practices. Our study addresses this by assessing lactic acid bacteria (LAB) in native Thai silkworm faeces, which accumulate as natural by-products during the rearing process. We conducted biochemical tests, including those for catalase, haemolytic activity, bile salt tolerance, antimicrobial activity, antibiotic susceptibility, and cell surface hydrophobicity, along with taxonomic classification. Out of 102 isolates, eight potential probiotics were selected, with five showing strong probiotic traits like acid and bile salt tolerance and cell surface hydrophobicity, enhancing gut survivability. These isolates also displayed antagonistic activity against pathogens like Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosa. Safety assessments confirmed their safety, with no haemolytic activity and sensitivity to antibiotics like chloramphenicol and amoxicillin. These LAB isolates (SP04, SP06, SP44, SP64, and SP67), identified as Enterococcus faecalis strain NBRC 100481, show promise as in vitro probiotics for silkworm rearing, calling for further in vivo evaluation. Full article

Background: Shiga toxin-producing Escherichia coli–haemolytic uremic syndrome (STEC-HUS) can result in kidney and neurological complications. Early volume-expansion therapy has been shown to improve outcomes, but caution is required to avoid fluid overload. Lung ultrasound scanning (LUS) can be used to detect fluid overload and may be useful in monitoring hydration therapy. Methods: This prospective observational pilot study involved children with STEC-HUS who were recruited from a regional paediatric nephrology centre. B-line quantification by LUS was used to assess fluid status at the emergency department (ED) admission and correlated with the decrease in patient weight from the target weight. A control group of children on chronic dialysis therapy with episodes of symptomatic fluid overload was also enrolled in order to establish a B-line threshold indicative of severe lung congestion. Another cohort of “healthy” children, without renal or lung-related diseases, and without clinical signs of fluid overload was also enrolled in order to establish a B-line threshold indicative of euvolemia. Results: LUS assessment was performed in 10 children with STEC-HUS at ED admission, showing an average of three B-lines (range 0–10). LUS was also performed in 53 euvolemic children admitted to the ED not showing kidney and lung disease (healthy controls), showing a median value of two B-lines (range 0–7), not significantly different from children with STEC-HUS at admission (p = 0.92). Children with STEC-HUS with neurological involvement during the acute phase and those requiring dialysis presented a significantly lower number of B-lines at admission compared to patients with a good clinical course (p < 0.001). Patients with long-term renal impairment also presented a lower number of B-lines at disease onset (p = 0.03). Conclusions: LUS is a useful technique for monitoring intravenous hydration therapy in paediatric patients with STEC-HUS. A low number of B-lines at ED admission (<5 B-lines) was associated with worse short-term and long-term outcomes. Further studies are needed to determine the efficacy and safety of an LUS-guided strategy for reducing complications in children with STEC-HUS. Full article

Certain Staphylococcus aureus strains harbour staphylococcal enterotoxin genes and hence can produce enterotoxin during their growth in food. Therefore, food can be a source of staphylococcal food poisoning, one of the most common food-borne diseases worldwide. Epidemiological data show that S. aureus is often present in raw milk cheeses, and consequently, cheeses are often the source of staphylococcal food poisoning outbreaks. The aim of this study was to determine the phenotypic characteristics of S. aureus isolates from fresh cheese, including antibiotic susceptibility; the presence of classical sea-see enterotoxin genes through molecular methods; and the isolate’s ability to produce SEA-SEE enterotoxins in vitro through reversed passive latex agglutination. A total of 180 coagulase-positive staphylococci were isolated from 18 out of 30 cheese samples, and 175 were confirmed as S. aureus through latex agglutination and API STAPH tests. All isolates possessed phenotypic characteristics typical for S. aureus, with certain variations in the egg yolk reaction (18.3% of the isolates showed a weak reaction and 28% no reaction at all) and haemolysis pattern (36.6% of the isolates produced double-haemolysis and 4.6% were non-haemolytic). Antibiotic resistance was observed in 1.1% of the isolates and to mupirocin only. Real-time PCR detected the sec gene in 34 (19.4%) isolates, but most isolates (80.6%) were not enterotoxigenic. For all 34 (19.4%) strains that carried the sec gene, the RPLA method detected the production of the SEC enterotoxin in vitro. For those enterotoxigenic strains, the possibility of enterotoxin production in fresh cheese could not be ruled out. Full article

Inflammatory bowel disease (IBD) is the term given to a heterogeneous group of chronic inflammatory diseases of the gastrointestinal tract (GI). These include ulcerative colitis (UC), where the inflammatory process involves only the intestinal mucosa, and Crohn’s disease (CD), where it can involve the entire wall of the GI in all of its sections. In addition to typical gastrointestinal complaints, IBD manifests with a range of extraintestinal symptoms involving inter alia the eyes, joints, skin, liver and biliary tract. These can cause a number of extraintestinal complications; of these, one of the most common is anaemia, usually resulting from nutritional deficiencies, especially iron, or chronic inflammation. When treating patients with IBD, it is important to consider the possibility of rare but serious complications, including autoimmune haemolytic anaemia (AIHA). This condition occurs in only 0.2 to 1.7% of UC cases and is even rarer in CD. AIHA is usually mild but can occur suddenly and cause very rapid anaemia. In the article presented here, we describe the case of a patient who developed AIHA two years after a diagnosis of CD, causing a life-threatening diagnostic and therapeutic challenge for the medical team. Full article