Immunomodulatory Effects of Resolvin D2 in a Model of Infection

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known as Specialized Pro-resolving Mediators (SPMs), synthesized endogenously from docosahexaenoic acid (DHA) by different immune cells including neutrophils and macrophages during infection and inflammation. In CLP sepsis, we observed that production of RvD2 in spleens had returned to basal levels by 48 hours after CLP surgery. Administering RvD2 (100 ng/mouse, i.v.) in CLP mice at this time point where endogenous RvD2 synthesis is low enabled CLP mice to clear blood bacteria more efficiently at 24 hours after administration compared to saline controls. There was no significant difference in plasma cytokine production. To further understand cellular and molecular mechanisms, we used flow cytometry to identify different immune cells in spleen and found that RvD2 treatment increased splenic neutrophils (Ly6G+) and myeloid-derived suppressor cells (MDSCs: CD11b+ Ly6G+ Ly6C+) compared to vehicle treated mice. RvD2 treatment increased oxidative burst in splenic neutrophils but not in splenic MDSCs compared to vehicle treated mice. These results provide evidence that RvD2 can expand splenic neutrophil and MDSC numbers to effect greater blood bacterial clearance even when given 48 hours after primary infection. When mice were challenged with P. aeruginosa (intranasally; 24 h after RvD2 treatment) we found that RvD2 increased bacterial clearance in lungs, increased alveolar macrophage numbers and reduced lung IL-23. These results suggest that late RvD2 administration boosted host defense to reduce infection and inflammation. This study provides insight into immunomodulatory effects of RvD2 in a 2-hit infection model of sepsis (Sundarasivarao et al., 2022)

Lipoxin A 4 (LxA 4 ) Promotes Reduction and Antibiotic Efficacy Against Pseudomonas aeruginosa Biofilm

Pseudomonas aeruginosa (P aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients P aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen We have previously shown that a Specialized Pro resolving Mediator ( Lipoxin A 4 (LxA 4 is a quorum sensing inhibitor which can reduce P aeruginosa virulence In this study, we examined the direct actions of LxA 4 and RvD 2 on P aeruginosa biofilm formation and virulence gene expression The influence of LxA 4 on antibiotic efficacy and the combined effects on biofilm formation were also investigated LxA 4 and RvD 2 reduced P aeruginosa biofilm formation and virulence gene expression LxA 4 increased ciprofloxacin inhibition on biofilm formation but did not affect ciprofloxacin’s action on non adherent bacteria On the other hand, LxA 4 increased bacterial killing action of imipenem but did not affect imipenem’s action on biofilm We also found that LxA 4 can increase ciprofloxacin’s bacterial killing ability in established biofilm Together these results suggest that LxA 4 has direct effects on P aeruginosa biofilm formation and can increase antibiotic efficacy directly

Hemangioma of the prostate - an unusual cause of lower urinary tract symptoms: Case report

<p>Abstract</p> <p>Background</p> <p>Hemangioma of the prostate gland is extremely rare and only a few cases have been reported. There have been several cases of hemangioma of posterior urethra, urinary bladder and periprostatic plexus in the literature, all presenting with hematuria or hematospermia. Diagnosis of prostatic hemangioma is difficult due to its rarity and unspecific symptoms such as hematuria, hematospermia or lower urinary tract symptoms. It cannot be detected by conventional examinations such as cystoscopy or standard rectal ultrasonography.</p> <p>Case presentation</p> <p>We present a case of prostatic hemangioma in an 84-year old male presenting with lower urinary tract symptoms. Bleeding has not been a feature in our case and diagnosis was not made until after operation. The patient was treated as a case of bladder neck outflow obstruction with transurethral resection of prostate gland and simultaneous bladder neck incisions. A period of self-catheterization was instituted due to postoperative urinary retention as the result of detrusor insufficiency.</p> <p>Conclusion</p> <p>Hemangioma of prostate gland is extremely rare and symptomatic prostatic hemangioma should be treated either by transurethral resection of prostate or laser evaporation.</p