Browsing by Subject "sepsis"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Cellulitis(2010-07-29) McCarthy, MarkCellulitis is an infection of the skin and soft tissues, typically due to bacteria. It begins with red, tender, swollen area of skin. It can spread into the blood and lymph nodes and cause sepsis, a severe infection of the entire body. It is important to seek medical attention when the first signs are present. Typically, early infections can be treated with oral antibiotics. If the infection worsens, intravenous (or medicine into your bloodstream) antibiotics may be necessary and patients may have to stay in the hospital to be monitored.Item Examining Helper T-cell Recovery After Sepsis(2015-08) Cabrera-Perez, JavierSepsis strikes 750,000 Americans every year with ~ 210,000 of these patients dying – far more than the number of deaths from prostate cancer, breast cancer, and AIDS combined. Some of these deaths occur during the acute, inflammatory stages of sepsis, but ~70% of these patients survive the initial infection, only to perish due to hospital-acquired infections. Most sepsis research has focused on understanding the acute, inflammatory stage of sepsis, but the increased susceptibility to secondary infections has led clinicians and researchers to believe that the chronic stage of sepsis is important and is characterized by immunosuppression. CD4 T-cells, essential for coordinating immune responses to opportunistic pathogens, are severely depleted during the acute stage of sepsis, but gradually recover throughout the immunosuppressive phase of sepsis. Despite the well-characterized immune cell apoptosis during sepsis, the impact of sepsis on protective T-cell responses (especially CD4 T-cells) against secondary pathogen challenge remains poorly understood. This dissertation presents a previously unappreciated mechanism of CD4 T-cell impairment during the immunosuppressive stage of sepsis. In the present study, we have studied sepsis immunosuppression by using Class II major histocompatibility complex tetramers to track endogenous, antigen specific CD4 T-cells, in order to examine a hypothesis: that the uneven recovery of the Ag-specific CD4 T-cell repertoire contributes to the alarming rate of infections in sepsis survivors. In addition, we have examined the impact of enteric microbial populations in the recovery of CD4 T-cells after sepsis. The results described present a previously unappreciated mechanism of CD4 T-cell impairment during the immunosuppressive stage of sepsis.Item Mechanisms Underlying Opioid Modulation of Gut Immunity(2014-08) Meng, JingjingOpioids are used widely by clinicians due to their potent analgesic activities and sedative properties. However, opioid use or abuse is associated with multiple adverse gastrointestinal (GI) symptoms and higher susceptibility to infection caused by pathogens with gut origin. Both clinical and laboratory studies implied that opioids showed suppressive effects on gut immunity and predisposed critically sick patients to infections while the mechanism underlying this defect is still unknown. In the present study we investigated how opioids modulate gut epithelial barrier function and immune responses of gut associated lymphoid tissue (GALT). We demonstrated significant bacterial translocation from gut lumen to mesenteric lymph node (MLN) and liver following morphine treatment in wild-type (WT) animals that was significantly attenuated in Toll-like receptor (TLR2 and 4) knockout mice. We further observed significant disruption of tight junction protein organization only in the ileum but not in the colon of morphine treated WT animals. Inhibition of myosin light chain kinase (MLCK) blocked the effects of both morphine and TLR ligands, suggesting the role of MLCK in tight junction modulation by TLR. Additionally we determined the immune responses of GALT to polymicrobial sepsis in the presence and absence of opioids by using a murine cecal ligation and puncture model. The results showed that opioids accelerated the mortality rate of polymicrobial sepsis. During sepsis progression, morphine treatment altered gut microbiome and subsequently promoted gram-positive bacterial dissemination, which induced excess IL-17A production in a TLR2-dependent manner, resulting in increased gut permeability, sustained inflammation and higher mortality. This study improved our understanding of the role of morphine in modulating gut barrier functions and the roles of GALT in infection susceptibility, which may provide the potential therapeutic targets for novel drug development and lead to more powerful strategy to control or prevent severe infectious diseases like sepsis especially in the opioid using and abusing population.