Effects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Models

Formyl peptide receptors (Fprs) are a G-protein-coupled receptor family mainly expressed on leukocytes. The activation of Fpr1 and Fpr2 triggers a cascade of signaling events, leading to leukocyte migration, cytokine release, and increased phagocytosis. In this study, we evaluate the effects of the Fpr1 and Fpr2 agonists Ac9-12 and WKYMV, respectively, in carrageenan-induced acute peritonitis and LPS-stimulated macrophages. Peritonitis was induced in male C57BL/6 mice through the intraperitoneal injection of 1 mL of 3% carrageenan solution or saline (control). Pre-treatments with Ac9-12 and WKYMV reduced leukocyte influx to the peritoneal cavity, particularly neutrophils and monocytes, and the release of IL-1β. The addition of the Fpr2 antagonist WRW4 reversed only the anti-inflammatory actions of WKYMV. In vitro, the administration of Boc2 and WRW4 reversed the effects of Ac9-12 and WKYMV, respectively, in the production of IL-6 by LPS-stimulated macrophages. These biological effects of peptides were differently regulated by ERK and p38 signaling pathways. Lipidomic analysis evidenced that Ac9-12 and WKYMV altered the intracellular lipid profile of LPS-stimulated macrophages, revealing an increased concentration of several glycerophospholipids, suggesting regulation of inflammatory pathways triggered by LPS. Overall, our data indicate the therapeutic potential of Ac9-12 and WKYMV via Fpr1 or Fpr2-activation in the inflammatory response and macrophage activation.

Perforated Meckel’s Diverticulum with Pancreatic and Gastric Heterotropia and Acute Peritonitis - A Case Report

Meckel’s diverticulum, the most common congenital anomaly of small bowel although usually silent, can cause complications like intestinal obstruction, bleeding, diverticulitis, perforation etc. We report a case, which presented with acute onset of severe pain in right iliac fossa which was clinically and sonographically diagnosed as acute appendicitis. Histopathological report of appendix was non specific findings. Four days after appendectomy patient again came with features of acute abdomen. X-ray abdomen showed free gas under diaphragm. Abdomen was explored with a midline incision, a perforated Meckel’sdiverticulum was found which was managed by wedge resection and repair of the ileum. Histopathological examination of specimen revealed diverticular wall with normal appearing intestinal mucosa and muscle coat which showed two heterotrophic tissues (pancreatic and gastric ) in the wall.These also showed features of perforation and acute peritonitis. This is probably the first case of Meckel’s diverticulitis with heterotropic pancreatic and gastric tissue in Bangladesh. J Shaheed Suhrawardy Med Coll 2020; 12(2): 115-118

Acute Diffuse Peritonitis Due to Spontaneous Rupture of an Infected Endometrioma: A Case Report

Background. Endometriosis is defined as a chronic, inflammatory, estrogen-dependent gynaecologic disease. It affects approximately 5–10% of reproductive-age women worldwide. Ovarian endometriosis is the most frequent form of this condition. Endometriotic cysts are found in about 17–44% of women diagnosed with endometriosis. It is well known, that ovarian endometriomas can cause infertility and chronic pelvic pain. Enlarging cysts can also cause ovarian torsion. In addition, ovarian endometriosis slightly increases the risk for ovarian cancer. The rupture of endometriotic ovarian cysts is an exceptional complication. According to the literature, the prevalence is less than 3% among women with endometriosis. The rupture of an ovarian endometrioma can cause acute peritonitis, which can lead to sepsis, septic shock and can be lethal. The occurrence of abscesses within an ovarian endometrioma is an extremely rare complication. Generally, the origin of infected endometriotic ovarian cysts is related to the previous invasive procedures involving pelvic organs or the use of intrauterine devices. Also, ovarian abscesses can be caused by the hematogenous or lymphatic spread of bacteria. Although, the literature points out that infection of endometriotic ovarian cysts can develop spontaneously. In these rare cases, reservoir and route of infection remains an enigma.Case report. A 49-year-old female was brought to the emergency room with severe generalized lower abdominal pain (6/10) and three days lasting fever. Abdominal examination revealed diffuse abdominal pain with anterior abdominal wall muscle tension. Painful solid masses were felt on both sides of the uterus during the pelvic examination. Cystic masses were detected in both ovaries during transvaginal sonography. Computer tomography (CT) of the abdomen and pelvis revealed abnormal changes in both ovaries. A small amount of free fluid was found in the pelvic cavity along with thickened pelvic peritoneum. Suspecting acute peritonitis and bilateral tubo-ovarian abscesses, surgical treatment was performed. Lower midline laparotomy with bilateral adnexectomy and abdominal lavage with 4000 ml normal saline were done. The outcome of peritonitis was evaluated using the Mannheim peritonitis index (MPI=17 – low risk of morbidity and mortality). The histopathological examination revealed the diagnosis of bilateral endometriotic cysts complicated with acute inflammation, with associated acute inflammation of both fallopian tubes. Microbiological cultures from the purulent fluid were negative.Conclusions. Although the occurrence of abscesses within an ovarian endometrioma is an extremely rare finding in clinical practice, it has to be considered by gynaecologists because it might result in a surgical emergency that can be life-threatening. Being aware of the risk factors of abscesses within an endometrioma can lead to an early diagnosis of this rare condition and help to avoid serious complications.

The role of ENOS polymorphism (C774T) in the progression of acute peritonitis and the formation of complications

In order to determine the role of ENOS (C774T) gene polymorphism in the progression of acute peritonitis and the formation of complications, a clinical and biochemical study of 40 patients with acute peritonitis was conducted. As a result of the study, it was proved that the early period of acute peritonitis is characterized by the development of endogenous intoxication, intensification of oxidative phenomena, hypercoagulation of the homeostasis system and inhibition of fibrinolysis, and in patients with acute peritonitis, carriers of the pathological TT genotype of the endothelial nitric oxide synthase gene, more pronounced deviations of homeostatic parameters are observed. Key words: acute peritonitis, genotype, DNA diagnostics, genetic testing of genotypes.

Population pharmacokinetics of intra-peritoneal gentamicin and the impact of varying dwell times on pharmacodynamic target attainment in patients with acute peritonitis undergoing peritoneal dialysis

While the use of intraperitoneal (i.p.) gentamicin is common in the treatment of peritoneal dialysis (PD)-related infections, the ability of these regimens to attain pharmacodynamic target indices of interest in blood and dialysate has not been widely reported. Pharmacokinetic (PK) data was obtained and analyzed from a multiple-dose PK study of i.p. gentamicin with 24 patients who received the drug at 0.6 mg/kg dose of body weight. The probability of target attainment (PTA) for indices of treatment success (i.p. peak/MIC ratio >10) and toxicity (plasma AUC < 120 mg*h/L) was determined for 0.3 to 1.2 mg/kg i.p. regimens every 24 h for dwell times of 2 to 6 hours and for the duration of 2-week course. In the peritoneum, successful PTA was achieved by all of the simulated regimens up to an MIC of 1 mg/L, and by doses equal to or greater than 0.6 mg/kg up to the MIC of 2 mg/L. At the susceptibility break point of 4 mg/L only the highest dose of 1.2 mg/kg is likely to provide adequate PTA. Probability of achieving exposure below the threshold of 120 mg*h/L in the daily AUC in plasma seems acceptable for all regimens at or below 0.6 mg/kg. Based on the model we developed, a gentamicin dose of 0.6 mg/kg is sufficient to treat organisms with an MIC of ≤2 mg/L without the risk of significant systemic exposure. The 1.2 mg/kg dose necessary to reach the pharmacodynamic target for efficacy at the clinical break point of 4 mg/L is likely to produce early toxic levels of exposure that is expected to be detrimental to the renal system.

P-BN10 Seasonal Variation of Presentation of Perforated Peptic Ulcer Disease: An Overview of Patient Demographics, Management and Outcomes in Northern Ireland

Background Perforated peptic ulcer disease is one of the most common causes of acute peritonitis. It carries significant mortality and morbidity. Several previous studies have reported a seasonal variation in presentation of patients with perforated ulcers. Here we present this study from a Northern Irish perspective on perforated peptic ulcers. Methods A retrospective cohort study was conducted on perforated peptic ulcer patients who presented to Altnagelvin Area Hospital emergency department between 2015 to 2020. Data on patient demographics, clinical presentation, investigations, management and outcomes were collected. Primary outcome was to investigate if seasonality was associated with incidence of perforated peptic ulcers. Follow-up data was also collected. Seasons were defined as per UK Met Office. Results Results: A total of 50 patients presented with perforated PUD. Male:female ratio was approximately 3:2. Peaks were noted in spring and winter. April was the most common month for presentation followed by December. Smoking was the most common risk factor followed by alcohol abuse. 14 patients (28%) were either very frail or had contained perforations and were conservatively managed. 3 deaths were noted (6%). 13 patients (26%) required ICU admission at some stage in their management. Conclusions Slight seasonal variation was noted in presentation of perforated peptic ulcers in our study with more common incidence in winter and spring months. The month of April was noted to have the peak incidence of the disease in our study.

A gastrointestinal Stromal Tumor of the Small Bowel Presenting as an Acute Peritonitis: A Case Report

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract, GISTs of the small bowel presenting as an acute peritonitis are rare, which necessitates emergency surgery. Presentation of Case: A 44-year-old women presented with severe abdominal pain and nausea. Physical examination revealed a tenderness and muscular defense around the lower abdomen. Laboratory data showed an elevated white blood cell count and C-reactive protein level. An enhanced computed tomography (CT) scan showed a 8 × 10 cm cystic mass in the lower abdomen, which contained air. Emergency laparotomy showed a giant perforated tumor that arose from the ileum, the tumor and affected segment of ileum were resected. the tumor was diagnosed as GIST in low-risk category, and imatinib mesylate was initiated, The patiente had an uneventful postoperative course and remains well. Discussion and Conclusion: Such rare cases can be diagnosed and treated properly with careful clinical evaluation, Computed tomography (CT) is the gold standard for imaging that is used to characterize any abdominal mass. Surgical resection is still the first-line treatment for patients with primary localized and resectable small bowel GIST and adjuvant chemotherapy with imatinib mesylate is indicated in patients with high-risk small bowel GIST.

Morphological features of the large intestine in experimental acute generalized peritonitis against the background of streptozotocin-induced diabetes

The work is a fragment of the research project “Pathogenetic features of the allergic and inflammatory processes course and their pharmacocorrection”, conducted by the Department of Pathological Physiology, Danylo Halytskyi Lviv National Medical University (state registration No. 0116U004503). The aim of the work: to study the morphological features of the colon in the dynamics of the development of experimental acute peritonitis on the background of streptozotocin-induced diabetes mellitus. Materials and Methods. The experiment used 48 white male rats. Diabetes mellitus in experimental animals was simulated by a single intraperitoneal injection of streptozotocin (Sigma) at a rate of 60 mg/kg, acute disseminated peritonitis – the introduction of 0.5 ml of 10 % filtered fecal suspension into the abdominal cavity. A morphological study of the colon in animals removed from the experiment on the first, third and seventh days of acute peritonitis on the background of concomitant diabetes mellitus was performed. Results and Discussion. Morphological examination of the colon of animals on the first day of experimental acute peritonitis in conditions of concomitant streptozotocin-induced diabetes mellitus revealed an increase in the size of the crypts due to stroma edema and lymphohistiocytic infiltration, slight perivascular edema in the subclavian edema. On the third day, thickening of the mucous membrane of the colon, a sharp increase in the depth of the crypts, uneven blood supply to the vessels in the submucosal layer with a predominance of perivascular edema were verified. On the seventh day, a decrease in the thickness of the mucous membrane due to the expansion of the crypts was visualized. Part of the epitheliocytes was in a phase of increased secretory activity, the other part was dystrophically altered, which stimulated increased lymphocytic and histiocytic infiltration. These changes were accompanied by activation of reactive processes and hyperplasia of lymphoid follicles on the first day of peritonitis on the background of streptozotocin-induced diabetes mellitus, and as the severity of purulent inflammation – hypoplasia of the lymphoid tissue and a decrease in local reactivity(the third and seventh days of the development of acute peritoneal burning in conditions of combined pathology).

Antimicrobial, Antibiofilm, and Anti-persister Activities of Penfluridol Against Staphylococcus aureus

Staphylococcus aureus has increasingly attracted global attention as a major opportunistic human pathogen owing to the emergence of biofilms (BFs) and persisters that are known to increase its antibiotic resistance. However, there are still no effective antimicrobial agents in clinical settings. This study investigated the antimicrobial activity of penfluridol (PF), a long-acting antipsychotic drug, against S. aureus and its clinical isolates via drug repurposing. PF exhibited strong bactericidal activity against S. aureus, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 4–8 and 16–32 μg/ml, respectively. PF could significantly inhibit biofilm formation and eradicate 24 h preformed biofilms of S. aureus in a dose-dependent manner. Furthermore, PF could effectively kill methicillin-resistant S. aureus (MRSA) persister cells and demonstrated considerable efficacy in a mouse model of subcutaneous abscess, skin wound infection, and acute peritonitis caused by MRSA. Notably, PF exerted almost no hemolysis activity on human erythrocytes, with limited cytotoxicity and low tendency to cause resistance. Additionally, PF induced bacterial membrane permeability and ATP release and further caused membrane disruption, which may be the underlying antibacterial mechanism of PF. In summary, our findings suggest that PF has the potential to serve as a novel antimicrobial agent against S. aureus biofilm- or persister-related infections.