Behavioural, metabolic, and endothelial effects of the TNF-α suppressor thalidomide on rats subjected to chronic mild stress and fed an atherogenic diet.

There is accumulating evidence suggesting that depression is a risk factor for cardiovascular diseases. This study aimed to examine the hypothesis that the proinflammatory cytokine TNF-α would partially explain the link between depression and atherosclerotic endothelial changes. Rats were distributed among 6 groups: (i) control group; (ii) group subjected to chronic mild stress (CMS); (iii) group fed a cholesterol-cholic acid-thiouracil (CCT diet); and (iv) CMS group fed the CCT diet and treated with the vehicle for 8 weeks. The last 2 groups were subjected to CMS-CCT and received thalidomide (THAL) or imipramine (IMIP). Rats were assessed behaviorally (sucrose preference, open field, and forced-swimming tests). TNF-α protein was assessed from the serum, aorta, and liver. Aortic TNF-α gene expression (assessed using RT-PCR), serum lipid profile, and insulin levels were measured. Endothelial function was assessed in isolated aortic rings. The THAL and IMIP groups showed ameliorated CMS-CCT-related behavioral changes. CMS-CCT-induced metabolic and endothelial dysfunctions were improved in the THAL group but were worsened in the IMIP group. RT-PCR showed a significant reduction of aortic TNF-α mRNA expression in the THAL and IMIP treatment groups. These data paralleled the findings for aortic immunohistochemistry. The THAL group, but not the IMIP group, showed improved CMS-CCT-induced changes in the vascular reactivity of the aortic rings. Thus, TNF-α provides a target link between depression, metabolic syndrome, and endothelial dysfunction. This could open a new therapeutic approach to address the comorbidities of depression.

Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression.

Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0.55% and 7.32%) (P<0.001). A highly significant correlation was noted between Tr ODI and the tumor grade, the nodal status, and the stage among adenocarcinomas. In conclusion, colonic tumors arise in a field of crypts with aberrations in CcOI expression. This aberration is linked to biologically aggressive tumors. CcOI immunostaining may be applied on mucosal samples from patients with colonic adenomatous polyps and patients with previous cancer colon resection to determine individuals who are in need for frequent colonoscopies and/or chemopreventive strategies. Future follow-up studies are warranted to determine the level of expression predictive of recurrence or progression.

Histopathological and electron microscopic study for different grades of inferior oblique muscle overaction.

PURPOSE: To correlate between the clinical degree of inferior oblique muscle (IO) overaction and the histopathological changes of the muscle. SETTINGS: Departments of Ophthalmology and Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. PATIENTS AND METHODS: Biopsies from 12 IO muscles were taken during strabismus surgery for cases of IO muscle overaction. One biopsy from a normal IO was taken as a control. All samples were examined under light microscopy and transmission electron microscopy. RESULTS: In light microscopy, all cases showed histopathological changes, in the form of degenerated and regenerating muscle fibers, increased fibrofatty infiltration, and mild variability of muscle fiber size. Hypertrophied nerve bundles also appeared in biopsies from patients with grade II and grade III IO overaction. Endomysial and perimysial fibrosis, mononuclear inflammatory infiltrates, and focal fatty infiltration were seen in biopsies from cases of grade III IO overaction. In electron microscopy, ultrastructural examination revealed an increased number of mitochondria associated with some degree of mitochondrial pleomorphism. Hypercontracted fibers, vacuoles, and fat droplets were also noticed. CONCLUSION: IO overaction is always accompanied by histopathological changes that differ in severity according to the clinical grading of the overaction. Changes in nerve fibers can also occur in severe cases.

Sensitivity and specificity of computed tomography and magnetic resonance imaging in the diagnosis of isolated sphenoid sinus diseases.

OBJECTIVES/HYPOTHESIS: The sphenoid sinus is uncommonly affected by inflammatory or neoplastic lesions. Initial onset of isolated sphenoid sinus diseases (ISSD) is generally asymptomatic. The objectives of this study were to estimate the sensitivity and specificity of computed tomography (CT) and magnetic resonance imaging (MRI) in diagnosing ISSD and establish guidelines to declare hidden ISSD through correlation of radiological diagnosis to final pathological diagnosis. STUDY DESIGN: A prospective cohort study. METHODS: There were 66 patients with isolated sphenoid sinus lesions presenting to Ain-Shams University Hospitals, Cairo, Egypt. Provisional diagnosis of ISSD was done by CT and MRI, followed by histopathologic and immunohistochemical staining, and if needed microbiological examination of resected specimens to establish the final diagnosis. RESULTS: Patients were classified into four groups according to the type of lesion: inflammatory, neoplastic, bony dysplastic disorders, and sphenoid sinus roof defect-related lesions. Radiological imaging provided the greatest diagnostic information and guided management. The sensitivity of CT and MRI in diagnosing inflammatory lesions was 95% versus 61%, whereas those of the neoplastic group were 72% and 100%, respectively. In the osseous group the sensitivity was 100% for both CT and MRI, whereas in sphenoid sinus roof defect the sensitivity was 50% and 100% for CT and MRI, respectively. CONCLUSIONS: Because of CT's superiority in defining the bony margins and MRI's superior soft tissue resolution, CT and MRI should be used in a complementary manner in the evaluation of isolated sphenoid sinus disease in addition to mapping the lesion better and identifying intracranial and intraorbital extension. The use of one modality only should be restricted to straightforward lesions.