Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: evidence for blood-pressure independent effect

Compound 21 (C21), selective agonist of AT2 receptors, shows antinflammatory effects in hypertension and nephroprotection in diabetes. The aim of this study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague Dawley rats. Cyclosporine-A (15mg/kg/day, i.p.) and cyclosporine-A plus C21 (0.3 mg/kg /day, i.p) were administered for 1 and 4 weeks. Control groups was left without any treatment. Blood pressure (plethysmographic method) and 24 hour albuminuria were measured once a week. At the end of the experiments, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and IV collagen expression.After 1 and 4 weeks, the rats treated with cyclosporine showed a significant increase (p <0.01) in blood pressure, no significant changes in albuminuria, a significant increase (p <0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared to the control rats. Treatment with C21 did not modify the cyclosporine dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (p <0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared to rats treated with cyclosporine.The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases

Thoracic aorta: anatomy and pathology

The aorta is the largest elastic artery in the human body and is classically divided into two ana-tomical segments, the thoracic and the abdominal aorta, separated by the diaphragm. The thoracic aorta includes the aortic root, the ascending aorta, the arch, and the descending aorta. The aorta's elastic properties depend on its wall structure, composed of three distinct histologic layers: intima, media, and adventitia. The different aortic segments show different embryological and anatomical features, which account for their different physiological properties and impact the occurrence and natural history of congenital and acquired diseases that develop herein. Diseases of the thoracic aorta may present either as a chronic, often asymptomatic disorder or as acute life-threatening conditions, i.e., acute aortic syndromes, and are usually associated with states that increase wall stress and alter the structure of the aortic wall. This review aims to provide an update on the dis-ease of the thoracic aorta, focusing on the morphological substrates and clinicopathological cor-relations. Information on anatomy and embryology will also be provided

Surgical management of extrafollicular variant of adenomatoid odontogenic tumor in the maxillary posterior region

Background. Adenomatoid odontogenic tumor (AOT) is a relatively uncommon benign neoplasm of odontogenic epithelial origin, accounting for less than 5% of odontogenic tumors. Case Report. The reported case describes morphological characteristics, clinical course, radiographic and histopathological features, and surgical therapy of an extrafollicular variant of AOT in the maxillary posterior region. An asymptomatic swelling on the left side in the posterior region of the maxilla, gradually increased since approximately 12 months, developed in a 16-year-old Caucasian female patient. Radiographic images revealed a well-defined, unilocular radiolucency, with some small foci of radiopacity inside, and root resorption of the first and second molars. On the base of the histological examination of the specimen retrieved by incisional biopsy, the diagnosis of AOT was made, and the conservative surgical enucleation of the lesion was performed. Discussion. The present case was reported in agreement with an extensive review, in which it was recommended to discontinue reporting classic follicular cases because their clinicopathological profile was well-known, but to continue reporting well-documented cases of the extrafollicular variant, with indication of the exact position. Conclusion. The present case was reported in order to expand the knowledge about the clinical behavior and surgical treatment of the extrafollicular variant of AOT

The rationale for liquid biopsy in colorectal cancer: focus on circulating tumor cells

Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood, which represents a precious source of biological material derived from both primary and metastatic tumors, has been named a 'liquid biopsy'. While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system. The analysis of viable CTCs at DNA, RNA and protein levels, as well as their expansion in vitro, may allow deep investigation of the features of metastases-initiating cells

An atypical death from Rapunzel syndrome: a case report

Trichotillomania is a psychiatric disorder characterized by recurring urges to pulling out hairs, eyelashes, or down in other parts of the body. Trichophagia, which is the urge to ingesting the pulled-out hairs, can cause Rapunzel syndrome, an unusual disorder where gastric trichobezoars can be found in the small intestine. Trichobezoars, amorphous masses composed of undigested food formed by hairs, can obstruct the gastrointestinal tract up to simulating symptoms typical of bowel obstruction. Rapunzel syndrome, named after Grimm's tale, may cause death, especially in the pediatric population, being it seldom over the age of 6; moreover, developing countries and environmental and familiar issues are listed as uncertain risk factors. The present case report deals with the death of a 4-year-old female occurred after lunch and following a series of vomit events; while no traumatic or pathological findings were revealed at the external examination, the autopsy revealed three large trichobezoars localized in the stomach and the small intestine. Despite death was due to gastrointestinal obstruction for multiple trichobezoars and collateral bronchoaspiration of dietary material, histological findings were totally non-specific, meaning that it is sometimes difficult to conclude that death is related to the primary pathological condition

Could the super-pulsed CO2 laser be used for oral excisional biopsies?

Background. The main purpose of a biopsy is microscopic examination and diagnosis. Keeping the margins of specimens safe and readable is always fundamental to detecting marginal infiltrations or malignant transformation. Numerous options and tools have been introduced for biopsy procedures. Lasers are one of these options that provide many enhancements to clinical and surgical biopsy procedures in comparison to scalpels. Objectives. The aim of the present study is to quantify the thermal artefacts in histological specimens obtained using a CO2 laser from different oral mucosal lesions and to evaluate if the resulting thermal effect hinders the histological examination. This aim is accomplished through quantitatively and qualitatively assessing the thermal effect in both the epithelium and connective tissue. Material and methods. A super-pulsed CO2 laser (10,600 nm) was used to obtain 10 excision biopsy samples. The parameters were a power of 4.2 W in focused mode and a frequency of 80 Hz in super-pulse mode. The histological analysis was performed with an optical microscope. Computerized imaging software was utilized to quantitatively evaluate the thermal effect in both the epithelium and connective tissue expressed in microns. Results. The thermal effect of the CO2 laser was limited to the surgical resection margins in all the specimens and did not hinder the histological analysis. Thermal artefacts were observed in 3 specimens. The range of thermal effects in the epithelial tissue was between 184 μm and 2,292 μm, while in the connective tissue it was between 133 μm and 2,958 μm. Conclusions. The resulting thermal effects of using a CO2 laser did not hamper the histological evaluation. Utilizing a laser in biopsy procedures should be tailored. Not only should laser parameters and safety margins be taken into consideration but also the working time, clinical accessibility, and the nature and water content of the tissue

Subtotal resection of vestibular schwannoma: evaluation with Ki-67 measurement, magnetic resonance imaging, and long-term observation

Purpose The aim of this study was to compare the postoperative clinical and radiological data of patients with vestibular schwannomas who were initially managed by near total resection (NTR) or subtotal resection (STR). The Ki-67 analysis results were compared with tumor regrowth to determine the presence of a correlation between this proliferative index and postoperative tumor regrowth. Study Design Seventeen adult patients (7 male, 10 female) were retrospectively reviewed. Nine (52.9%) and eight (47.1%) patients underwent NTR and STR, respectively. Postoperative clinical and radiological data associated with vestibular schwannoma growth were compared with the Ki-67 immunohistochemical analysis results. Results Evidence of clinically significant regrowth was observed in four (23.5%) patients. Patients who underwent NTR had a lower rate/incidence of tumor regrowth than did patients who underwent STR. Patients with a higher Ki-67 index had the highest tumor regrowth rates. Conclusions Our study indicates that assessment of the Ki-67 index may be useful for determining the probability of regrowth of vestibular schwannomas when only partial removal is accomplished

Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression

Purpose Down-regulation of thyroid hormone receptor beta (THRβ) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRβ mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical–biological features. Methods Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRβ gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRβ. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart. Results THRβ transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRβ expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression. Conclusions Our results demonstrate that down-regulation of THRβ is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Nonischemic left ventricular scar and cardiac sudden death in the young

Nonischemic Left Ventricular Scar (NLVS) is a pattern of myocardial injury characterized by midventricular and/or subepicardial gadolinium hyper enhancement at cardiac magnetic resonance, in absence of significant coronary artery disease. We aimed to evaluate the prevalence of NLVS in juvenile sudden cardiac death and to ascertain its aetiology at autopsy. We examined 281 consecutive cases of sudden death of subjects aged 1 to 35 years of age. NLVS was defined as a thin, grey rim of subepicardial and/or midmyocardial scar in the left ventricular free wall and/or the septum, in absence of significant stenosis of coronary arteries. NLVS was the most frequent finding (25%) in sudden deaths occurring during sports. Myocardial scar was localized most frequently within the left ventricular posterior wall, and affected the subepicardial myocardium, often extending to the midventricular layer. On histology it consisted of fibrous or fibro-adipose tissue. Right ventricular involvement was always present. Patchy lymphocytic infiltrates were frequent. Genetic and molecular analyses clarified the aetiology of NLVS in a subset of cases. ECG recordings were available in over half of subjects. The most frequent abnormality was the presence of low QRS voltages (< 0,5 mV) in limb leads. In serial ECG tracings, the decrease in QRS voltages appeared, in some way progressive. NLVS is the most frequent morphologic substrate of juvenile cardiac sudden death in sports. It can be suspected based on ECG findings. Autopsy study and clinical screening of family members are required to differentiate between Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia and chronic acquired myocarditis