Clinical guidelines in early detection of oral squamous cell carcinoma arising in oral lichen planus: a 5-year experience

In recent years, studies on the malignant potential of oral lichen planus (OLP) provided clinical evidence that patients affected by OLP have an increased risk to develop oral squamous cell carcinoma (OSCC); nevertheless, controversies still exist as to whether OLP has inherent predisposition to become malignant, or not. We believe extremely careful management of OLP patient is mandatory, and the aim of this paper is to illustrate our clinical guidelines in evaluating the possible risk of transformation in OLP lesions. Five-hundred and two patients (311 women and 191 men) affected by OLP regularly undergo follow-up examination in our Department. Patients' ages range from 18 to 83 years, with a mean of 55.4 years (57.5 for women and 53.9 for men); minimal follow-up period is 4 months, with a maximum of 12 years. In our group of OLP patients in the past 5 years we detected 24 carcinomas: excluding three cases in which diagnoses of OLP and OSCC were synchronous and three patients who had a history of tobacco use, thus possible malignant transformation of OLP would appear to be 3.7%. Clinical criteria used in our follow-up allowed us to detect 28.5% of tumours as in situ OSCC, 38% as microinvasive OSCC, 28.5% as stage I OSCC and 4.7% as stage II OSCC, with a remarkable improvement in prognosis compared to our previous study in which we adopted different criteria.     

Beneficial effects of ACE-inhibition with zofenopril on plaque formation and low-density lipoprotein oxidation in watanabe heritable hyperlipidemic rabbits

The effects of angiotensin-converting enzyme (ACE)-inhibition with zofenopril on the development of atherosclerosis and low-density lipoprotein (LDL) oxidation were determined in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Rabbits received either placebo (n = 6) or 0.5 mg/kg/day of zofenopril (n = 6). After 6 weeks of treatment, the computer-assisted analysis revealed that zofenopril reduced the aortic and common carotid corrected cumulative lesion area by 34% and 39%, respectively (p < 0.05 vs placebo-treated group). The intimal/medial ratio of the largest fatty streaks was 0.426+/-0.158 in the zofenopril-treated group and 0.875+/-0.238 in the placebo-treated group (p < 0.05). Furthermore, we found in the zofenopril-treated group smaller lesions with an intimal/medial ratio of zofenopril also reduced plasmatic LDL oxidation, as shown by significant reduction of malondialdehyde content (p < 0.01) and relative agarose gel mobility (p < 0.05), as well as by the prolongation of the lag-time (p < 0.05). Compared to zofenopril-treated rabbits, arterial sections of the placebo-group had significant increase in the intimal presence of macrophages-derived foam cells (p < 0.05), ox-LDL (p < 0.01), and native LDL (p < 0.01) detected by immunocytochemistry with RAM-11, MDA2 and NP1533975 monoclonal antibodies, respectively. To investigate the amount of platelet accumulation in the atherosclerotic plaque we also measured platelet-associated radioactivity. Autologous platelets were labeled with 111Indiumoxine and injected intravenously. After 2 hours, WHHL were sacrificed and arterial sections were counted for platelet-associated radioactivity. In the placebo-treated group, platelet radioactivity was 0.52+/-0.12 equivalent of radioactivity per mg of tissue in the common carotid and 0.25+/-0.18 in the abdominal aorta; in contrast, rabbits treated by zofenopril had 0.20+/-0.12 in the common carotid and 0.06+/-0.01 in the abdominal aorta. These data indicate that ACE-inhibition with zofenopril has antiatherosclerotic and antioxidant effects in WHHL-rabbits. Our results also shows that these effects could be linked to a reduced wall-associated platelet deposition at the site of atherosclerotic lesions.     

Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucocorticoid receptor in vivo

Histamine, vascular endothelial growth factor, acetylcholine, oestrogen as well as fluid shear stress activates a mechanism that recruits heat shock protein 90 to the endothelial nitric oxide synthase. The interaction between Hsp90 and eNOS enhances the activation of the enzyme in cells and in intact blood vessels leading to NO production. Intraplantar administration of carrageenan (50 microl paw(-1)) to mice causes an oedema lasting 72 h. Geldanamycin (0.1, 0.3, 1 mg kg(-1)), a specific inhibitor of Hsp-90, that inhibits endothelium-dependent relaxations of the rat aorta, mesentery and middle artery inhibits carrageenan-induced mouse paw oedema in a dose dependent manner. Co-administration to mice of dexamethasone (1 mg kg(-1)) with geldanamycin (0.3 mg kg(-1)) at anti-inflammatory dose causes a loss of the total anti-inflammatory effect of each agent alone. RU 486 (10 mg kg(-1)), a well known glucocorticoid receptorial antagonist, does not inhibit oedema formation but prevents the anti-inflammatory action of dexamethasone (1 mg kg(-1)). Similarly, RU 486 prevents the anti-inflammatory action of geldanamycin (0.3 mg kg(-1)). In conclusion we have described for the first time that geldanamycin, an inhibitor of Hsp90 dependent signal transduction, is anti-inflammatory in vivo implying that Hsp90 is critical for pathways involved in carrageenan-induced paw oedema. In addition the ability of GA to block NO release and reduce oedema formation suggests a therapeutic rationale for specific inhibitors of Hsp90 as potential anti-inflammatory drugs.     

Type 1 diabetic mice are protected from acetaminophen hepatotoxicity.

Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t1/2, increased volume of distribution (Vd), and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of 14C-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via 3H-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair.     

Fine-needle aspiration cytology of angiolymphoid hyperplasia with eosinophilia: a case report with electron microscopy and immunohistochemistry

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon vascular inflammatory lesion usually involving the dermis or subcutaneous tissue of the head-neck region of middle-aged women. Histologically, this lesion shows a florid proliferation of vessels lined by particular endothelial cells and an inflammatory infiltrate composed of lymphocytes and eosinophils. The fine-needle aspiration (FNA) cytology of a nodular lesion in the retroauricolar region of a 18-yr-old woman showed spindle-shaped and polygonal cells with vesicular nuclei and deeply eosinophilic cytoplasm containing well-defined vacuoles in a background of eosinophils and lymphocytes. These features were consistent with a proliferation of epithelioid endothelial cells, and a diagnosis of ALHE was suggested. The histology confirmed the preoperatory diagnosis, and ultrastructural and immunohistochemical studies further demonstrated the endothelial nature of epithelial-appearing cells. Because the clinical appearance of the lesion may mimic a large number of benign and malignant diseases, a preoperatory diagnosis of ALHE is rarely made. The FNA cytology may represent a simple and reliable method with which to study and diagnose proliferations of epithelioid endothelial cells.     

Biological characterization of recombinant human follicle stimulating hormone isoforms.

It has been established that follicle stimulating hormone (FSH) circulates in the bloodstream as a heterogeneous population of molecules. Individual FSH isoforms, while displaying identical amino acid sequences, differ in their extent of post-translational modification. As a result of these variations, the FSH isoforms exhibit differences in overall charge, degree of sialic acid or sulphate incorporation, receptor binding affinity and plasma half-life. Taking advantage of the fact that these forms can be separated from each other on the basis of their charge, we have evaluated in rats the metabolic clearance rates of the acidic [with an isoelectric point (pI) 4.8) isoforms of recombinant human FSH (rhFSH) obtained after chromatofocusing. The less acidic isoform group was found to have a faster clearance from the circulation in rats as compared with the acidic isoform group. This finding is in agreement with the lower bioactivity in vivo (as determined by the Steelman-Pohley assay) of the less acidic isoform group, compared with the acidic one. The mass spectra of the two groups of isoforms showed a difference in the sialic acid content thus highlighting the importance of these residues on the in-vivo activity of FSH. Conversely, when the two groups of isoforms were tested in vitro by using the Y1 human FSH receptor (Y1 hFSHR) assay and a reporter gene assay, no significant differences in the biological activities between these preparations were detected when test concentrations were based on mass.     

Predictive factors of urinary retention following prostate brachytherapy

PURPOSE: To evaluate the incidence and duration of urinary retention requiring catheterization and the factors predictive for these end points. METHODS AND MATERIALS: Two hundred eighty-two patients treated with prostate brachytherapy alone were evaluated. Clinical and treatment-related factors examined included: age, baseline International Prostate Symptom Score (IPSS), presence of comorbidity, planning ultrasound target volume (PUTV), postimplant prostate CT scan volume, the CT:PUTV ratio, number of seeds inserted, number of needles used, use of neoadjuvant hormones, procedural physician, clinical stage, Gleason score, and pretreatment PSA. Dosimetric quality indicators were also examined. RESULTS: Urinary obstruction after prostate brachytherapy developed in 43 (15%) patients. The median duration of catheter insertion was 21 days (mean 49, range 1-365). Univariate analysis demonstrated that presence of diabetes, preimplant volume, postimplant volume, CT:PUTV ratio, number of needles, and dosimetric parameters were predictive for catheterization. However, in multivariate analysis, only the baseline IPSS, CT:PUTV ratio, and presence of diabetes were significant independent predictive factors for catheterization. CONCLUSION: Baseline IPSS was the most important predictive factor for postimplantation catheterization. The extent of postimplant edema, as reflected by the CT:PUTV ratio, predicted for need and duration of catheterization. The presence of diabetes was predictive for catheterization, but may relate to the absence of prophylactic steroids, and therefore requires further evaluation.