ABSTRACT
Severe soft tissue infections caused by Aeromonas dhakensis, such as necrotizing fasciitis or cellulitis, are prevalent in southern Taiwan and around the world. However, the mechanism by which A. dhakensis causes tissue damage remains unclear. Here, we found that the haemolysin Ahh1, which is the major virulence factor of A. dhakensis, causes cellular damage and activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome signalling pathway. Deletion of ahh1 significantly downregulated caspase-1, the proinflammatory cytokine interleukin 1ß (IL-1ß) and gasdermin D (GSDMD) and further decreased the damage caused by A. dhakensis in THP-1 cells. In addition, we found that knockdown of the NLRP3 inflammasome confers resistance to A. dhakensis infection in both THP-1 NLRP3-/- cells and C57BL/6 NLRP3-/- mice. In addition, we demonstrated that severe soft-tissue infections treated with antibiotics combined with a neutralizing antibody targeting IL-1ß significantly increased the survival rate and alleviated the degree of tissue damage in model mice compared control mice. These findings show that antibiotics combined with therapies targeting IL-1ß are potential strategies to treat severe tissue infections caused by toxin-producing bacteria.
Subject(s)
Aeromonas , Gram-Negative Bacterial Infections , Hemolysin Proteins , Inflammasomes , Soft Tissue Infections , Animals , Mice , Aeromonas/metabolism , Anti-Bacterial Agents , Caspase 1/metabolism , Hemolysin Proteins/metabolism , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Macrophages/metabolism , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Soft Tissue Infections/immunology , Soft Tissue Infections/microbiology , Gram-Negative Bacterial Infections/immunology , Gram-Negative Bacterial Infections/microbiologySubject(s)
Catheters, Indwelling , Device Removal/statistics & numerical data , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Peritoneal Dialysis/adverse effects , Peritonitis/mortality , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Peritonitis/etiology , Peritonitis/therapy , Prognosis , Recurrence , Renal Dialysis , Taiwan/epidemiologyABSTRACT
Pineal apoplexy is a rare clinical presentation of pineal parenchymal tumors. We report the curative treatment of a case of pineal parenchymal tumor of intermediate differentiation with spontaneous apoplectic hemorrhage. This case is shown through computed tomography and magnetic resonance imaging of the brain, and is confirmed via histopathological studies. Recurrent upward gaze paresis was observed after the stereotactic biopsy. The paresis required an expeditious tumor resection. The mechanism of the pineal apoplectic hemorrhage remains unclear although it has been observed in different pineal region lesions. Clinical and radiological evidence of the cure 5 years post-surgery is available.
ABSTRACT
The association between cerebellar medulloblastoma and syringomyelia is uncommon and only found in pediatric patients. To date, adult medulloblastoma associated with syringomyelia has not been reported in the literature. Paroxysmal bradycardia is an uncommon clinical manifestation in posterior fossa tumors and likely to be vagally mediated via brainstem preganglionic cardiac motor neurons. This report introduces the diagnosis and treatment of a case of adult medulloblastoma associated with syringomyelia, which presented with paroxysmal bradycardia.