Apoptosis as a mechanism for burn-induced gastric mucosal injury

ABSTRACTIntroduction: Severe thermal burns disturb tissue homeostasis of many organs, but the exact mechanisms of gastric mucosa changes are not yet clear. Various cellular mechanisms, such as cell activation, mitochondrial dysfunction, free oxygen radicals and cytokine overproduction may be involved in this process.Aim: The aim of this study was to assess the levels of malondialdehyde (MDA), apoptotic proteins Bax and Bcl-2 in normal gastric mucosa and to test the hypothesis that oxidative stress activation induces apoptotic processes in the stomach after experimental thermal trauma.Materials and Methods: Under anesthesia, the shaved rats` dorsum was exposed to 90° C bath for 10 s to induce third-degree burn injury, involving 30% of the total body surface area. We determined the tissue level of MDA, a lipid peroxidation marker, by spectrophotometric method and the apoptosis of epithelial cells in gastric mucosa, which was immunohistochemically determined at the level of Bcl-2 and Bax in burn trauma.Results: The gastric MDA level was higher (p<0.01) in the burned group compared to the control group 24 hours after thermal injury. The gastric mucosa in the treated group showed congestion, degenerative changes in the surface epithelium, focal destruction of glandular epithelium with formation of acute erosions. Bax expressed moderately in epithelial cells, predominantly in the basal parts of the gastric glands, while in the control group protein content was localized in the same region, but it was weak. Bcl-2 protein in the control group revealed nuclear expression in surface epithelium, while in the basal layer of gastric mucosa the expression was moderate and mainly cytoplasmic. In the burned group, Bcl-2 expression was more diffuse, nuclear and cytoplasmic, but cytoplasmic expression was weak.Conclusion: Thermal skin trauma induces gastric mucosal injury through the activation of lipid peroxidation, increase of pro-apoptotic Bax protein expression and decrease of anti-apoptotic Bcl-2 protein expression in epithelial cells. We suggest that apoptosis is a possible mechanism for structural changes in the gastric mucosa

ANGIODYSPLASIA OF THE SMALL INTESTINE AND COLON: A REPORT OF THREE CASES.

INTRODUCTION: Angiodysplasia is a rare lesion (0.82% prevalence) characterised by enlarged, abnormally dilated blood vessels in the mucous or submucous sheath of the gastrointestinal tract. This condition clinically manifests with acute or chronic bleeding from the gastrointestinal tract. Typically the diagnosis is based on endoscopic findings and histological characteristics of the distorted vascular structures. Angiodysplasia is quite a common finding in elderly patients. However, the reasons for the anomaly observed with advancing age are yet to be revealed. CASE REPORT: The aim of this report is to highlight three cases of intestinal angiodysplasia histologically confirmed in patients at 47, 60 and 66 years of age.   Histological examination using light microscopy revealed different in size and shape dilated, filled with blood vessels surrounded by oedematous, inflamed stroma in the mucosal and submucosal layer of the intestine. CONCLUSION: Angiodysplasia is considered to be the second most common cause of gastrointestinal bleeding. This makes an adequate histologically confirmed diagnosis of this anomaly crucial for a patient`s quality of life

Effects Of Melatonin Suplementation On Body Mass Index In A Diet-Induced Obesity Rat Model

Introduction: Оbesity has been labelled as a “non-infectious pandemic of our time”. It increases the risk of several debilitating diseases, including cardiovascular disorders, diabetes mellitus, tumors, and other pathologies. Up to date both therapeutic and preventive approaches have been largely unsuccessful. At the present time body mass index (BMI) is considered the most common anthropometric method to diagnose obesity. According to a variety of in vivo and in vitro studies, exogenous melatonin has a pronounced effect on carbohydrate and lipid metabolism. Furthermore, supplementation with melatonin improves oxidative stress and insulin resistance preventing hypertrophy of the adipose tissue and body weight gain.Aim: We evaluated the effect of melatonin supplementation on BMI and retroperitoneal fat mass in diet-induced obesity rat model.Materials and Methods: Male Wistar rats (n = 32), provided with standard rat chow and tap water freely available, were randomly divided into four groups as follows: control group – rats received standard rodent diet and tap water; melatonin group – rats received standard rodent diet and tap water, and melatonin administered per os (4 mg/kg/24h); fructose group – rats received standard rodent diet and tap water supplemented with 20% fructose; and fructose plus melatonin group – rats received standard rodent diet and tap water supplemented with 20% fructose, and melatonin administered per os (4 mg/kg/24 h). At the end of the experimental period, the animals were sacrificed, zoometric measurements were taken and BMI was calculated.Results: Statistically significant differences were observed between the anthropometric parameters of the experimental groups. When compared with the control group, fructose-supplemented rats showed a remarkable increase in retroperitoneal fat mass and BMI. In contrast, groups supplemented with melatonin showed significant reductions in these parameters.Conclusion: Melatonin supplementation reduces fructose-induced obesity. In particular, body weight, retroperitoneal fat mass and BMI were remarkably decreased in melatonin-treated groups

Experimental Study on the Effects of Melatonin Supplementation on Obesity-Induced Endothelial Dysfunction // Изследване на ендотелната дисфункция при експериментален модел на затлъстяване и суплементация с мелатонин

Obesity is a medical and social problem due to associated comorbidities. It is believed that endothelial dysfunction (ED) links the latter with obesity and triggers the development of cardiovascular disorders (CVD). Furthermore, ED precedes the development of CVD. For this reason, scientific research is putting much effort into finding new and efficient therapeutic approaches for possible therapeutic approaches to ED. Both oxidative stress (OS) and chronic inflammation play an essential role in the pathogenesis of ED. Hence, an efficient therapeutic approach may be linked to the application of endothelial protectors with antioxidant and anti-inflammatory properties. Application of the latter may reveal mechanisms involved in endothelial protection and ways of correction. Currently, scientific literature provides insufficient data on the possibilities of detection, prevention and correction of reversible stages of ED. This makes experimental animal studies a promising research field. We developed a research hypothesis to establish reversible ED in a fructose-induced experimental model of obesity and melatonin supplementation and to explain the link between pathological remodelling of a. abdominalis, markers of OS and chronic obstructive low-grade inflammation. The present study aims to elucidate molecular mechanisms of both endothelial damage and protection in an experimental model of obesity, along with possible therapeutic strategies.Затлъстяване е медико-социален проблем поради съпътстващите коморбидни състояния. Патогенетичен фактор свързващ, затлъстяването с тези компликации се счита развитието на ендотелна дисфункция (ЕД). Последната, на фона на затлъстяване, се смята за отключващ механизъм за развитие на ССЗ. Търсенето на възможности за терапевтично въздействие върху ЕД е перспективните направления в профилактиката и лечението на кардиометаболитните заболявания. Функциите на ендотела се нарушават преди морфологичните и клиничните признаци на ССЗ. Оксидативен стрес (ОС)и хронично възпаление играят важна роля в развитието на ЕД. Проучванията в тази насока представляват предизвикателство от научна гледна точка. Изследването на ендотелопротектори с антиоксидантни и противовъзпалителни свойства, би могло да разкрие механизми за протекция/корекция на вече съществуваща ЕД. В литература са представени изследвания, които са недостатъчни за да се направи комплексна оценка за увреждането на ендотела в обратими прояви на ЕД. Перспективно направление е възможността да се моделира ЕД при животни. Ние създадохме хипотеза с цел да установим обратими прояви на ЕД и комплексната функционална връзка между промените в стената на аорта, маркери на ОС и хронично нискостепенно възпаление при фруктозо-индуциран модел на затлъстяване и суплементация с мелатонин. С настоящото проучване целим изясняване на молекулярните механизми на увреждане и протекция на ендотела при затлъстяване и възможности за терапевтично повлияване

Radiation-induced low grade fibromyxoid sarcoma of the larynx: a case report and literature review

Low grade fibromyxoid sarcoma (LGFMS) is an uncommon variant of fibrosarcoma with high risk of local recurrence, immense metastatic potential and frequently protracted period between tumour presentation and metastasis. This unusual malignancy rarely affects the region of the head and neck which makes cases of laryngeal LGFMS extremely infrequent. To date, LGFMS of the larynx has been scatteredly mentioned in the literature. Neither incidence nor causes and risk factors for laryngeal LGFMS have been clarified so far. To the authors’ knowledge, this is the first case report that discusses the clinical course, imaging diagnosis, histopathological evaluation and surgical approach to radiation-induced laryngeal LGFMS.We present a case of a 70-year-old man who developed a LGFMS after previous radiotherapy (RT) for squamous cell carcinoma (SCC) of the larynx. The latency period between the time of radiation exposure and the diagnosis of LGFMS was twenty-seven months. After re-confirming the diagnosis with second biopsy and extensive imaging evaluation the patient was subjected to an open partial resection of the larynx. Owing to the rarity of the tumour, there is no established protocol with follow-up recommendations.This case highlights the importance of considering the RT history of the patient in order to monitor radiotherapy-related complications, including the occurrence of LGFMS

Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic Injury in Experimental Burns

Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn model. We hypothesized that melatonin gastric protection may be related to the activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30% total body surface area (TBSA) rat burn model, melatonin (10 mg/kg, i.p.) was injected immediately and 12 h after thermal skin injury. Via light immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)). Thermal trauma in burned animals, compared with the controls, increased the expression of pro-apoptotic Bax protein (1.37 (0.94–1.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06–1.23), p &lt; 0.001) in epithelial cells, and elevated Bax/Bcl-2 ratios (p &lt; 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98–1.61) and 1.16 (1.01–1.25), p &lt; 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74–0.96), p &lt; 0.01) and upregulated Nrf2 (1.55 (1.52–1.65), p &lt; 0.001) levels. It also augmented Bax (1.68 (1.5–1.8), p &lt; 0.001) and Bcl-2 expressions (1.96 (1.89–2.01), p &lt; 0.0001), but reduced Bax/Bcl-2 ratios (p &lt; 0.05). Our results suggest that experimental thermal trauma induces oxidative gastric mucosal injury. Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid peroxidation attenuation, and Bax/Bcl-2 ratio modification as well