Milos Z. Milosavljevic

Galectin-3 Plays an Important Pro-inflammatory Role in the Induction Phase of Acute Colitis by Promoting Activation of NLRP3 Inflammasome and Production of IL-1β in Macrophages

BACKGROUND AND AIMSnGalectin-3 [Gal-3] is an endogenous lectin with a broad spectrum of immunoregulatory effects: it plays an important role in autoimmune/inflammatory and malignant diseases, but the precise role of Gal-3 in pathogenesis of ulcerative colitis is still unknown.nnnMETHODSnWe used a model of dextran sulphate sodium [DSS]-induced acute colitis. The role of Gal-3 in pathogenesis of this disease was tested by evaluating disease development in Gal-3 deficient mice and administration of Gal-3 inhibitor. Disease was monitored by clinical, histological, histochemical, and immunophenotypic investigations. Adoptive transfer was used to detect cellular events in pathogenesis.nnnRESULTSnGenetic deletion or pharmacological inhibition of Gal-3 significantly attenuate DSS-induced colitis. Gal-3 deletion suppresses production of pro-inflammatory cytokines in colonic macrophages and favours their alternative activation, as well as significantly reducing activation of NOD-like receptor family, pyrin domain containing 3 [NLRP3] inflammasome in macrophages. Peritoneal macrophages isolated from untreated Gal-3(-/-) mice and treated in vitro with bacterial lipopolysaccharide or DSS produce lower amounts of tumour necrosis factor alpha [TNF-α] and interleukin beta [IL-1β] when compared with wild type [WT] cells. Genetic deletion of Gal-3 did not directly affect total neutrophils, inflammatory dendritic cells [DCs] or natural killer [NK] T cells. However, the total number of CD11c+ CD80+ DCs which produce pro-inflammatory cytokines, as well as TNF-α and IL-1β producing CD45+ CD11c- Ly6G+ neutrophils were significantly lower in colons of Gal-3(-/-) DSS-treated mice. Adoptive transfer of WT macrophages significantly enhanced the severity of disease in Gal-3(-/-) mice.nnnCONCLUSIONSnGal-3 expression promotes acute DSS-induced colitis and plays an important pro-inflammatory role in the induction phase of colitis by promoting the activation of NLRP3 inflammasome and production of IL-1β in macrophages.

Deletion of IL-33R attenuates VEGF expression and enhances necrosis in mammary carcinoma

Interleukin-33 (IL-33)/IL-33 receptor (IL-33R, ST2) signaling pathway promotes mammary cancer growth and metastasis by inhibiting anti-tumor immunity. However, the role of IL-33/IL-33R axis in neoangiogenesis and tumor necrosis is not elucidated. Therefore, the aim of this study was to investigate the role of IL-33/IL-33R axis in mammary tumor necrosis. Deletion of IL-33R (ST2) gene in BALB/c mice enhanced tumor necrosis and attenuated tumor growth in 4T1 breast cancer model, which was associated with markedly decreased expression of vascular endothelial growth factor (VEGF) and IL-33 in mammary tumor cells. We next analyzed IL-33, IL-33R and VEGF expression and microvascular density (MVD) in breast tumors from 40 female patients with absent or present tumor necrosis. We found significantly higher expression of IL-33, IL-33R and VEGF in breast cancer tissues with absent tumor necrosis. Both, IL-33 and IL-33R expression correlated with VEGF expression in tumor cells. Further, VEGF expression positively correlated with MVD in perinecrotic zone. Taking together, our data indicate that IL-33/IL-33R pathway is critically involved in mammary tumor growth by facilitating expression of pro-angiogenic VEGF in tumor cells and attenuating tumor necrosis. These data add an unidentified mechanism by which IL-33/IL-33R axis facilitates tumor growth.

Evaluation of brivaracetam: a new drug to treat epilepsy

ABSTRACT Introduction: High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters. Areas covered: Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy. It reduces baseline-adjusted focal seizure frequency per week from 7.3 to 12.8% over placebo. Adverse events rate in patients with brivaracetam is not higher than in patients with placebo. Expert opinion: Brivaracetam is an important step forward in the treatment of therapy-resistant partial-onset seizures with or without secondary generalization. Its development was systematic and targeted. Due to its efficacy and excellent safety profile, it is likely that brivaracetam will be often prescribed. In future, efficacy and safety of brivaracetam should be tested in monotherapy settings and also in the first-line therapy of partial-onset seizures.

Total Endoprothesis of Hip Joint: Characteristics and Application in Patients in the Central Region of Serbia

Total hip arthroplasty is a surgical procedure in which the hip joint is replaced with an artificial one. Performance of this procedure requires knowledge of the anatomical features of the joint, the characteristics of the endoprosthesis, and the needs and pathological and physiological characteristics of the patient. This retrospective analysis includes the data contained in 874 medical histories of patients of both sexes implanted with a unilateral total hip endoprosthesis who were treated at the Orthopedic Clinic of the Clinical Center, Kragujevac, from January 1st, 2009 to December 1st, 2014. Analysis of the data revealed that 69.3% of the patients were women. The most common type of implanted prosthesis was the cementless one, and the most frequent indication was degenerative joint damage. Total arthroplasty of the hip joint has become one of the most common interventions in orthopedic surgery. The increasing need for this method of treatment required the development of new biomaterials, as well as new types of prosthesis, which, in the future, will decrease the occurrence of adverse reactions and complications during and after implantation of the prosthesis, as well as extending their useful life.

Appendicular endometriosis: Case presentation and review of the literature

Endometriosisis an estrogen-dependent inflammatory disease which occurs in 5-50% of women in the reproductive period. May be asymptomatic or can cause extensive gynecological disorders, from pelvic pain to infertility in 45% of patients. The patient, aged 23, was admitted to hospital Surgery Clinic, because of pain in the lower right part of the abdomen, with a high temperature of 39 degrees, pain and disgust, without vomiting. Pain was present last 4 days, and the other symptoms have occurred in the last 24 hours. Clinical examination, painful sensitivity was found with abdominal tightness, particularly pronounced in the lower right quadrant of the abdomen. Findings of rectal and vaginal examination were normal. Laboratory findings were in normal range, except for C-reactive protein in the presence of leukocytosis. Computed tomography of the abdomen it was noticed, retrocecal, enlarged appendix diameter 20 mm. Laparotomy, under general endotracheal anesthesia were identified, retrocecal, oedematous- enlarged appendix, dark brown in color, with no signs of peritonitis. Right ovary and the terminal portion of the small intestine were macroscopically visible without macroscopic changes. Appendectomy was performed, and the operative material was sent for histopathological analysis. Standard microscopic examination with immunohistochemical analysis confirmed the diagnosis of acute appendicitis with endometriosis. The postoperative course was regular and the patient was discharged from hospital on the fifth day in a good general condition. Endometriosis of the appendix is very rare and can be a cause of acute appendicitis. Preoperative diagnosis is almost impossible, and the importance of the precise histological analysis is particularly high among women treated for infertility.

Prenatally diagnosed fetal omphalocele at 11 week gestation — a case report

Omphalocele is the most common congenital defect of the abdominal wall and in a large percentage of cases it is associated with chromosomal anomalies. In this case report during the regular ultrasound examination at 11 weeks of gestation, omphalocela, whose scope was 90% of fetal abdomen, was diagnosed. Karyotype analysis showed the presence of chromosomal aberrations 47 XX + 18 (Edwards syndrome). After the presentation of the severity of congenital anomalies and characteristic of the Edwards syndrome patient decided to terminate the pregnancy.

A rare case of coexistent intralobar and extralobar pulmonary sequestration

In the pathology of respiratory tract, sequestration presents as a non-functional lung tissue with no communication with tracheobronchial tree. It represents a rare congenital bronchopulmonary and vascular malformation, which occurs at a frequency of 0.1 to 6%. Intralobar and extralobar sequestrations are extremely rare congenital anomalies, especially if they occur at the same time in a patient. Proper diagnosis and appropriate surgical therapy, in the absence of associated anomalies, provide an excellent prognosis. In this paper, we are describing the simultaneous presence of intralobar sequestration (ILS) in the lower lobe of the left lung and extralobar sequestration (ELS) which is positioned on the aortic arch, in a 53 years old man. Two years post surgery, there is no recurrence or any patomorphological and functional disorders in the respiratory tract.

Synovial sarcoma of carotid space

Synovial sarcomas are malignant tumors of mesenchymal origin, extremely rarely located in the area of the head and neck. Histologically they can be monophasic, biphasic or poorly differentiated with numerous differential diagnostic dilemmas. A 54-year-old male with synovial sarcoma of the carotid space is presented. The patient refused suggested postoperative radiotherapy and, nine months after the primary surgery, local relapse was verified. Following surgical resection of the local relapse, postoperative radiotherapy treatment was utilized. Ten months after the second surgery, secondary deposits in the lungs were radiographically confirmed, and local recurrence was noticed again. Treatment was continued with symptomatic therapy and eleven months later patient died. Synovial sarcomas of the carotid space are extremely rare, with complex surgical approaches and pathohistological differential diagnostic dilemmas. Diagnosis requires determination of the immunophenotype of the tumor cells, whereas therapy requires an aggressive surgical approach and postoperative radiotherapy.

Jejunogastric intussusception as complication of gastric surgery

Intussusception in adults is a very rare entity that occurs in only 5% of all intestinal obstructions. Most often, in 66% of cases, intussusception is localized to the small intestine, while jejunogastric intussusception is very rare and occurs in 0,1%. Since the first case of jejunogastric intussusception after gastrojejunostomy was described by Bozzi in 1914, fewer than 200 isolated cases of postoperative intussusception after gastric surgery have been reported.Here we present a case of anterograde jejunogastric intussusception, 15 years after radical subtotal gastrectomy with Billroth II anastomosis in a 71-year-old man.