Intestinal Barrier Dysfunction, Bacterial Translocation and Inflammation: Deathly Triad in Sepsis

Sepsis, as a complex entity, comprises multiple pathophysiological mechanisms which bring about high morbidity and mortality. The previous studies showed that the gastrointestinal tract is damaged during sepsis, and its main symptoms include increased permeability, bacterial translocation (BT), and malabsorption. BT is the invasion of indigenous intestinal bacteria via the gut mucosa to other tissues. It occurs in pathological conditions such as disruption of the intestine’s ecological balance and mucosal barrier permeability, immunosuppression, and oxidative stress through transcellular/paracellular pathways and initiate an excessive systemic inflammatory response. Thereby, recent clinical and preclinical studies focus on the association between sepsis and intestinal barrier dysfunction. This chapter overviews the current knowledge about the molecular basis of BT of the intestine, its role in the progress of sepsis, detection of BT, and actual therapeutic approaches

Cholesterolosis in routine histopathological examination after cholecystectomy: What should a surgeon behold in the reports?

AbstractIntroduction: Cholecystectomy is one of the most common surgical procedures. Postoperative investigation of cholecystectomy specimen has a great value since histopathological reports may document some entities with significant clinical consequences. The aim of this study was to evaluate the association between cholesterolosis and the reports indicating some histopathological alterations in symptomatic cholecystitis. Methods: This paper is based on a retrospective study. Histopathological reports of 432 cholecystectomy specimens between January 2011 and June 2013 were reviewed. Three reports were excluded due to perioperative diagnosis of cancer. Reports of 429 cholecystectomy specimens of the acute and symptomatic chronic cholecystitis patients were analyzed. Standardization of the reporting was questioned. Age, gender, histopathological wall thickness of gallbladder, reporting rates of acute inflammation, cholesterolosis, polypoid lesions, epithelial hyperplasia, gastric or intestinal metaplasia, dysplasia and incidental cancer were investigated and compared between patients with and without cholesterolosis. Reported rates of histopathological findings were comparable between patients under and over 60 years old and patients with and without reported cholesterolosis. Results: Reported histopathological findings were presented as acute inflammation in 46 (10.7%), cholesterolosis in 79 (18.4%), gallbladder polypoid lesions in 7 (1.6%), epithelial hyperplasia in 16 (3.7%), metaplasia of any type in 34 (7.9%) of 429 patients. Dysplasia was excluded whereas one incidental gallbladder carcinoma was reported. Epithelial hyperplasia and metaplasia were found to be related to age. Gallbladder wall thickness was decreased with cholesterolosis. However, only a correlation between cholesterolosis and gender or metaplasia was noted. Conclusion: Recent study suggests that cholesterolosis is somehow associated with metaplasia. Thus, surgeons should carefully interpret the histopathology reports based on unusual or exceptional findings corresponding to the cholecystectomy specimens. Any abnormal finding in the reports should be investigated in terms of the progress of the pathology and also its clinical consequences

Massive inguinoscrotal bladder hernia causing hydronephrosis: Two cases

• Complete bladder herniation are very rare compared to incomplete bladder herniation. • Massive scrotal cystocele is usually defined with voiding symptoms. • CT, ultrasonography and retrograde cystogram should be performed to determine the involvement of the bladder in cases of massive inguinoscrotal hernias. • In massive scrotal hernia cases, bladder can protrude with the ureter causing hydronephrosis on the affected side. • It is necessary to place urinary catheter to empty the urinary bladder to manage the pain and to decrease the risk of injury of bladder during the surgery

A rare complication of inguinal hernia: Small bowel perforation due to falling down while walking

Small bowel perforation can occur either spontaneously or due to traumatic causes. Non-traumatic spontaneous small bowel perforation can be caused by various reasons including infectious, inflammatory, congenital, metabolic, vascular or neoplastic origins. Small bowel injury due to blunt trauma is a rare phenomenon compared to other intraperitoneal organ injuries, and frequently appears in high-energy trauma. Yet, even low-energy trauma can cause small bowel perforation in the presence of an inguinal hernia. Several cases of small bowel perforation after abdominal trauma or direct trauma to the hernia site are previously reported, however perforation of the small bowels following a low-energy trauma, such as a fall while marching, is a rare condition. A 65-year-old male admitted to the ER following a sudden onset of severe abdominal pain after 4hours following a fall while marching. Physical examination revealed a reduced right indirect inguinal hernia. There was diffuse tenderness and defense in the abdomen. The patient was operated due to the acute abdomen after 6hours following a falling down, and primary repair was performed. The patient was discharged on the fifth postoperative day. With this case report, it is aimed to increase the awareness of the surgeons regarding this rare complication.</p

Pharmacological Protection against Ischemia-Reperfusion Injury by Regulating the Nrf2-Keap1-ARE Signaling Pathway.

Ischemia/reperfusion (I/R) injury is associated with substantial clinical implications, including a wide range of organs such as the brain, kidneys, lungs, heart, and many others. I/R injury (IRI) occurs due to the tissue injury following the reestablishment of blood supply to ischemic tissues, leading to enhanced aseptic inflammation and stimulation of oxidative stress via reactive oxygen and nitrogen species (ROS/RNS). Since ROS causes membrane lipids’ peroxidation, triggers loss of membrane integrity, denaturation of proteins, DNA damage, and cell death, oxidative stress plays a critical part in I/R pathogenesis. Therefore, ROS regulation could be a promising therapeutic strategy for IRI. In this context, Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates the expression of several factors involved in the cellular defense against oxidative stress and inflammation, including heme oxygenase-1 (HO-1). Numerous studies have shown the potential role of the Nrf2/HO-1 pathway in IRI; thus, we will review the molecular aspects of Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response element (ARE) signaling pathway in I/R, and we will also highlight the recent insights into targeting this pathway as a promising therapeutic strategy for preventing IRI

Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research.

Background: Intestinal ischemia is a highly morbid and mortal condition with no specific treatment. The present study aimed to investigate the effects of cyclooxygenase (COX) inhibition synchronized with nitric oxide (NO) release and endothelin (ET) receptor blockade on oxidative stress, inflammation, vasoconstriction, and bacterial translocation which occur during ischemia-reperfusion (I/R) injury in in-vivo rat intestinal I/R model. Materials and methods: 36 male Wistar rats were randomly divided into six groups (n = 6). Superior mesenteric artery blood flow (SMABF) was recorded; SMA was occluded for 30 min; SMABF was re-recorded at the beginning of the reperfusion phase. Rats were sacrificed after the reperfusion period of 60 min. Blood and tissue samples were obtained. Acetylsalicylic acid (ASA), NO-ASA, flurbiprofen (FLUR), and Tezosentan (TS) were administered 15 min after ischemia. Histopathological examination, bacterial translocation, and biochemical analysis were performed in plasma and tissue samples. Results: SMABF difference, mean Chiu's score and bacterial translocation were increased in the I/R group and decreased in the treatment groups. Plasma LDH, transaminases, intestinal fatty acid-binding protein (I-FABP), TNF-alpha, ICAM-1, interferon-gamma (IFN-gamma) and proinflammatory cytokine panel; tissue lipid peroxidation, MPO, xanthine oxidase (XO), NO, NF-kB levels and the expression of TNF-alpha were significantly elevated in the I/R group and markedly decreased in the treatment groups. The tissue antioxidant status was decreased in the I/R group and increased in the treatment groups. Conclusion: It is suggested that NO-ASA, TS, and FLUR can be introduced as promising therapeutics to improve intestinal I/R injury