Immunohistochemical Characterization of Canine Prostatic Intraepithelial Neoplasia

The development of prostate cancer is believed to be a multistep process, progressing sequentially from normal epithelium, to prostatic intraepithelial neoplasia (PIN) and, finally, to invasive neoplasia. Malignant stem cells within the basal cell layer of the prostatic epithelium are believed to play an important role in the failure of androgen-ablation therapy that occurs in the most advanced form of prostate cancer. The aim of the present study was to immunohistochemically characterize the lesions of canine PIN. Prostatic tissue from five dogs with PIN was compared with normal prostate tissue from nine further dogs. There was an increase in the number of basal epithelial cells in lesions consistent with PIN as defined by expression of the nuclear protein p63. These lesions had elevated expression of proliferating cell nuclear antigen (PCNA) and heterogeneous labelling for the nuclear androgen receptor (AR). These findings suggest that the basal cells present in PIN may play a role in canine prostate carcinogenesis and that the proliferation of these cells occurs despite the heterogeneous expression of the AR. (C) 2009 Elsevier Ltd. All rights reserved.

Immunohistochemical Analysis of Proliferating Cell Nuclear Antigen (PCNA) in Dental Follicles of Impacted Third Molars

This study investigated the immunodetection of PCNA in epithelial components of dental follicles associated with impacted third molars without radiographical and morphological signs of pathosis. A total of 105 specimens of dental follicles associated with impacted third molars with incomplete rhizogenesis (between Nolla`s stage 6 and 9) were surgically removed from 56 patients. Epithelial cell proliferating was determined by using immunohistochemical labeling. Statistical analysis was performed using the Fisher exact test. Of the 105 dental follicles collected, 6 were PCNA-positive (approximate to 6%). The specimens with squamous metaplasia and epithelial hyperplasia had higher rates of positivity for PCNA, as well as those with proliferative remnants of odontogenic epithelium. In conclusion, this study shows that dental follicles at this stage of development have low proliferative potential, but suggests that squamous metaplasia, hyperplasia of the epithelial lining and presence of proliferative odontogenic epithelial rests in the connective tissue may be early signs of developing lesions of odontogenic origin.

Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver

Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM. Journal of Endocrinology (2011) 211, 55-64

Complement 4 phenotypes and genotypes in Brazilian patients with classical 21-hydroxylase deficiency

The aim of this work was to analyse C4 genotypes, C4 protein levels, phenotypes and genotypes in patients with the classical form of 21-hydroxylase deficiency. Fifty-four patients from 46 families (36 female, 18 male; mean age 10.8 years) with different clinical manifestations (31 salt-wasting; 23 simple-virilizing) were studied. Taq I Southern blotting was used to perform molecular analysis of the C4/CYP21 gene cluster and the genotypes were defined according to gene organization within RCCX modules. Serum C4 isotypes were assayed by enzyme-linked immunosorbent assay. The results revealed 12 different haplotypes of the C4/CYP21 gene cluster. Total functional activity of the classical pathway (CH50) was reduced in individuals carrying different genotypes because of low C4 concentrations (43% of all patients) to complete or partial C4 allotype deficiency. Thirteen of 54 patients presented recurrent infections affecting the respiratory and/or the urinary tracts, none of them with severe infections. Low C4A or C4B correlated well with RCCX monomodular gene organization, but no association between C4 haplotypes and recurrent infections or autoimmunity was observed. Considering this redundant gene cluster, C4 seems to be a well-protected gene segment along the evolutionary process.

Three-dimensional description and mathematical characterization of the parasellar internal carotid artery in human infants

Inside the `cavernous sinus` or `parasellar region` the human internal carotid artery takes the shape of a siphon that is twisted and torqued in three dimensions and surrounded by a network of veins. The parasellar section of the internal carotid artery is of broad biological and medical interest, as its peculiar shape is associated with temperature regulation in the brain and correlated with the occurrence of vascular pathologies. The present study aims to provide anatomical descriptions and objective mathematical characterizations of the shape of the parasellar section of the internal carotid artery in human infants and its modifications during ontogeny. Three-dimensional (3D) computer models of the parasellar section of the internal carotid artery of infants were generated with a state-of-the-art 3D reconstruction method and analysed using both traditional morphometric methods and novel mathematical algorithms. We show that four constant, demarcated bends can be described along the infant parasellar section of the internal carotid artery, and we provide measurements of their angles. We further provide calculations of the curvature and torsion energy, and the total complexity of the 3D skeleton of the parasellar section of the internal carotid artery, and compare the complexity of this in infants and adults. Finally, we examine the relationship between shape parameters of the parasellar section of the internal carotid artery in infants, and the occurrence of intima cushions, and evaluate the reliability of subjective angle measurements for characterizing the complexity of the parasellar section of the internal carotid artery in infants. The results can serve as objective reference data for comparative studies and for medical imaging diagnostics. They also form the basis for a new hypothesis that explains the mechanisms responsible for the ontogenetic transformation in the shape of the parasellar section of the internal carotid artery.