Long-term type 1 diabetes mellitus creates a pro-atherogenic environment conducive to early atherosclerosis in rats.

INTRODUCTION: Experimental models are essential for clarifying the pathogenesis of atherosclerosis in the context of diabetes mellitus (DM). We aimed to evaluate the presence and the magnitude of several factors known to promote atherogenesis, and to assess the potential of a pro-atherogenic environment to stimulate the development of atherosclerotic lesions in a rat model of long-term type 1 DM. MATERIALS AND METHODS: Six control and five DM Wistar rats were evaluated. DM was induced at 11 weeks of age using streptozotocin (STZ; 60 mg/kg, intraperitoneal). Animals were monitored up to 38 weeks of age, when plasma glucose, lipid profile, and markers specific for systemic inflammation, endothelial dysfunction, and oxidative stress were measured. The amount of fat within the aortic wall was assessed semiquantitatively using Oil Red O staining. RESULTS: Diabetic rats presented significantly higher plasma glucose (p < 0.001), total cholesterol and triglycerides (both p = 0.02), high-sensitivity C-reactive protein (p = 0.01), and vascular endothelial growth factor (p = 0.04) levels, and significantly lower interleukin-10 (p = 0.04), superoxide dismutase (p < 0.01), and glutathione peroxidase (p = 0.01) levels than the control rats. Mild (grade 1) atherosclerotic lesions were observed in the aortic wall of 80% of the diabetic rats and in none of the control rats. CONCLUSIONS: This study presents a STZ-induced type 1 DM rat model with one of the longest follow-ups in the literature. In this model, long-term DM created a highly pro-atherogenic environment characterised by hyperglycemia, dyslipidemia, systemic inflammation, endothelial dysfunction, and oxidative stress that resulted in the development of early aortic atherosclerotic lesions.

Metformin plus temozolomide-based chemotherapy as adjuvant treatment for WHO grade III and IV malignant gliomas.

PURPOSE: Glioblastoma multiforme (GBM) remains one of the most devastating diseases known to man and affects more than 17,000 patients in the United States alone every year. This malignancy infiltrates the brain early in its course and makes complete neurosurgical resection almost impossible. Recent years have brought significant advances in tumor biology, including the discovery that many cancers, including gliomas, appear to be supported by cells with stem-like properties. In the current study we have investigated the effects of combining metformin with the standard treatment-of-care, as this drug, already used in the treatment of diabetes mellitus, has shown surprising results in the treatment of breast cancer, being also associated with lower mortality in several other malignancies. METHODS: The subjects of the current study were 8 patients with newly diagnosed high-grade gliomas, operated at the Department of Neurosurgery - Clinical University Emergency Hospital, Cluj Napoca. Tumor tissue cultures were established and characterized using immunofluorescence microscopy and PCR analysis and the sensitivity to metformin, epidermal growth factor (EGF) and temozolomide (TMZ) was tested. Microvascular density (MVD) assay was performed on the tumor samples. RESULTS: Seven of the 8 cases had a positive correlation between the number of endothelial cells, the phenotype of isolated tumor cells and the response to adjuvant chemoradiotherapy. The isolated tumor cells had a stem-like behavior, being resistant to conventional drugs. In most cases there was no statistical significant difference between TMZ alone and TMZ plus EGF arms, but there was a important difference between TMZ alone and TMZ plus metformin arms in 6 of the cases. CONCLUSION: New drugs and targeted molecular therapies are important for future therapeutics, but sometimes we must not exclude drugs already used in the clinic that might have remarkable results. Such is the case of metformin, a drug used for decades in the treatment of type 2 diabetes mellitus that has proven to enhance the effect of TMZ in the treatment of breast cancer and, starting with this paper, of brain cancer.

Experimental Model of Mixed Intestinal Infarction in Rabbit.

The article presents an experimental model of the mixed intestinal infarction obtained by ligaturing of the cranial mesenteric artery (CMA) and of the cranial mesenteric vein (CMV) in rabbit.

[Complications of palpebral epitheliomas: diagnostic, therapeutic, and prognostic implications]. / Complicatii ale epitelioamelor palpebrale--implicatii diagnostice, terapeutice si prognostice.

PURPOSE: To illustrate two cases of palpebral tumors that determined local complications, with consequences on the preoperative diagnosis and the surgical treatment (case 1) and on the functional prognosis of the eye (case 2). METHOD: The history and evolution of the cases, the surgical techniques, the histopathological reports and the anatomical and functional results are described and analyzed. RESULTS: In case 1, the extension of the tumor led to a considerable tissular defect that claimed for a long and hard surgery for the anatomical and functional repair of the region. In case 2, the vegetant evolution of the tumor determined the irritation of the cornea and consecutive corneal ulcer that perforated, with the functional loss of the eye. CONCLUSIONS: The two cases are revealing aspects that are less frequent in the ophthalmic practice. They signalize, besides the deffisient adresability of the patient, the problem of the "territorial dispute" over the palpebral surgery between different specialties.

Eosinophilic esophagitis.

Eosinophilic esophagitis is a chronic, immune-mediated disorder, isolated to the esophagus. Current theory suggests that the former may be caused by cell-mediated food hypersensitivity or may be a subset of eosinophilic gastrointestinal disease, an autoimmune disorder. During the last decade, the increasing prevalence of EoE has been recognized in pediatric populations. Reports support the efficacy of dietary restriction or corticosteroid therapy. Aditional research is needed to determine etiology, allow earlier clinical recognition and improve treatment. Because no single symptom, endoscopic finding or histopathologic feature is pathognomonic, the diagnosis can frequently be challenging. The current article reviews the possible etiology, clinical presentation, diagnosis, and treatment of this disorder, which has been called not only allergic esophagitis (which may be the most important cause), but also eosinophilic esophagitis, primary eosinophilic esophagitis, and idiopathic eosinophilic esophagitis.

Nervous structure of Meckel's diverticulum in children.

Meckel's diverticulum, being considered as the most frequent malformation of the digestive tract, has been largely presented in scientific papers, but a complete physiopathological mechanism for its natural history has not been yet described. We have studied the nervous system and the differences observed in eight Meckel's diverticulums with enteric or ectopic gastric mucosa, using specific immunohistochemical markers. It has been noted a significantly higher density of myenteric nerve fibers in areas with enteric mucosa compared with the areas with gastric heterotopias, while the transition zone had intermediate nerve fibers density. The ileal wall near the diverticulum had a myenteric plexus density similar to gastric mucosa intradiverticular area. The density of Meckel's diverticulum myenteric plexuses determines the local peristalsis. The enteric type mucosa diverticulums has more intense peristaltic activity which leads more frequent to intussusception or, in case of intraluminal obstruction, might be also involved in germ spreading and progression of infectious process. The lower density of Auerbach's plexus nerve fibers in cases with gastric heterotopia Meckel's diverticulum determines less effective drainage of diverticular content, favoring the contact of intradiverticular mucosa with acid secretion of gastric mucosa area. The gastric mucosa's defense mechanisms and the intense peristaltic activity in the zone with enteric mucosa offer a certain protection against the apparition of intradiverticular ulcerative lesions, which usually are observed on the ileum, near the diverticulum. The age related decreasing number of myenteric nerve fibers density explains the higher frequency of Meckel's diverticulum complications in children.

Granulomatous cheilitis of Miescher: the diagnostic proof for a Melkersson-Rosenthal syndrome.

BACKGROUND: The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is being characterized by the following triad: facial nerve palsy, swelling of the lips and fissured tongue. However, the monosymptomatic form is more common and the typical manifestation is facial edema and/or enlargement of the lips. CASE REPORT: We report a case of monosymptomatic MRS with a positive biopsy of granulomatous cheilitis. CONCLUSIONS: In the daily practice as a pediatrician, it is not usual to diagnose a patient as having MRS. We consider that this is partly because of misdiagnosis. We therefore believe that this case report will supply additional information, in the scope of recurrent facial paralysis and orofacial edema in both children and adults.

EBV in pediatric neoplasia--intensity of infection as independent prognostic factor.

RATIONALE: Cancer disease is continuously rising worldwide as far as its incidence is concerned. Efforts were made in order to identify the etiologic factors. A good example for exogenous factors is Epstein Barr virus (EBV) which is largely spread worldwide, over 90% of the adult general population being infected by it. EBV is believed to be implicated in Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, etc. OBJECTIVE: In this paper, we will try to present the experience of two centers in Cluj County involved in the treatment of pediatric cancer, focusing on the influence of the presence of Epstein Barr virus in the outcome of the neoplasia. METHODS AND RESULTS: we took into account the clinical data regarding histology, stage of the disease, titer of specific antibodies for EBV, serological and imagistic evaluations of the patients treated in a retrospective consecutive manner for 5 years--2005-2010. Regarding our cohort of 120 patients, we analyzed the items in the paper in detail together with the statistical analysis and searched for a link between the intensity of the infection of EBV and response, disease, free survival, toxicities of the treatment. DISCUSSION: there are few data concerning the influence of EBV regarding the outcome of pediatric neoplasia. The published studies suggest a positive influence of EBV especially in Hodgkin disease mixed cellular subtype. In this study, EBV negative patients do better than the EBV positive, but the infection with EBV protects the patients against hematological toxicities.

Experimental study on histological changes in the sinus membrane following sinus lift.

UNLABELLED: The aim of this study is to assess the histological changes in the sinus mucosa adjacent to the alloplastic material used for subantral augmentation. MATERIALS AND METHODS: The study included ten sheep and a dog. The first group of five sheep underwent a sinus lift procedure, using PerioGlas as an augmentation material; the second similar group of sheep was the control group. The dog underwent a sinus lift procedure, with PerioGlas augmentation, after the sinus membrane was intentionally perforated and two implants were placed in the same operative step. RESULTS: Scanning electron microscopy (SEM) of the sinus mucosa in the control group revealed cells without cilia between goblet cells. The cilia were uniformly arranged in sections in the same direction. Changes occurred in the sinus mucosa after grafting, such as drastic reduction of ciliated cells, which seemed to be replaced by goblet cells. In all sheep undergoing grafting, generalized fibrosis was found in the mucosal area that came into contact with PerioGlas. In two of the sheep in which grafting was performed, mucoid cysts with pseudo stratified ciliated epithelium were present. Even when the sinus mucosa was perforated (in the dog), the inflammatory process developed in the mucosa did not prevent the integration of the graft and implants. In conclusion, following the sinus lift procedure, changes occur in the sinus membrane to adapt to the new situation, without the appearance of chronic or acute suppurative processes.

The effect of distraction rate on bone histological and histomorphometrical properties in an ovine mandible model.

UNLABELLED: Lengthening the mandible by distraction osteogenesis (DO) is nowadays a well-recognized technique in maxillofacial surgery. This study compared two different distraction rates and evaluated histological and histomorphometrical properties of the distracted bone in an experimental ovine mandible model with the goal of elaborating a universally accepted distraction protocol. STUDY DESIGN: Tissue blocks of regenerated bone were harvested from twelve young adult sheep. DO was performed on the mandibular midline after five days of latency period. The sheep were divided into two groups. The first group underwent activation of 0.8 mm÷day during 12 days resulting in 9.6 mm of new bone while the second group followed a geometric rate pattern of 0.2 mm - three days, 0.4 mm - three days, 0.8 mm - three days and 1.6 mm - three days resulting in 9 mm of new bone. The regenerated bone was histologically and histomorphometrically analyzed after 30, 45 and 60 days of consolidation. The relative osteoid volume (OV÷TTV) was significantly increased in the geometric rate distraction group (p=0.015) comparing with linear distraction group while the relative bone volume (BV÷TTV) was significantly increased in the linear distraction group (p=0.019) compared to the geometric distraction group.

Normal hepatic growth: study of the proliferative capacity and apoptosis of the normal liver during childhood.

We explored the mechanism of normal hepatic growth in children by evaluating the proliferation index (with Ki-67 antibody) and apoptosis index (with the ApopTag kit). The proliferative index is almost constant, but the level of apoptosis is very low in childhood and increases with age. Thus the growth of the liver in children is not due to a high proliferation index, but to a very low apoptosis index.