Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Modulation of dihydroxyphenylacetaldehyde extracellular levels in vivo in the rat striatum after different kinds of pharmacological treatment

We recently identified the direct product of dopamine (DA) by monoamine-oxidase (MAO) activity, dihydroxyphenylacetaldehyde (DOPALD) in the trans-striatal dialysate. Based on these findings, in this work, we directly measured the variations in DOPALD levels after various kinds of pharmacological treatment in rat striatal extracellular fluid. Using both reversible and irreversible MAO inhibitors, we found that MAO-A inhibition suppressed, whereas MAO-B inhibition did not modify DOPALD levels in the dialysate. The vesicular DA uptake blocker Ro 4-1284 led to an increase in extracellular DA and DOPALD, whereas the increase in extracellular DA obtained after administration of the plasma membrane DA uptake blocker GBR-12909 occurred without concomitant changes in DOPALD extracellular levels. Microinfusions of DA through the dialysis probe or systemic administration of L-DOPA increased striatal DOPALD to a greater extent compared with other DA metabolites, both in intact and in 6-hydroxydopamine (6-OHDA)-lesioned striatum. This study indicates that the direct product of MAO activity within the rat striatum derives from the activity of the isoenzyme MAO-A. The assay of DOPALD, together with DOPAC, represents a reliable tool to measure directly, in freely moving animals, DA oxidative metabolism. As recent studies have shown that microinfusions of exogenous DOPALD might induce cell death, pharmacological modulation of DOPALD levels might also be relevant for an understanding of the mechanisms involved in DA neurotoxicity.     

Diagnostic and referral accuracy of family doctors in melanoma screening: effect of a short formal training.

Little is known about ability of family doctors in the diagnosis and management (decision as to dermatologic referral) of pigmented skin lesions. We sought to evaluate the impact of a short formal training on diagnostic and referral accuracy of family doctors in melanoma screening. A formal 4-h training session was given to a sample of 41 practising family doctors working in the Florence health district, Tuscany, Italy. Before and after the course, a diagnostic test with a series of clinical images of pigmented skin lesions including four invasive melanomas (mean thickness, 1.5 mm; range, 0.8-2.2) was performed (open intervention study). Although only 46.8% of observations yielded a correct melanoma diagnosis at baseline, 96.1% of melanoma observations were correctly associated with intention to refer the lesion to dermatologist. After training, the percentage of correct melanoma diagnosis significantly increased (76.2%, P=0.01) while no further improvement was found as to sensitivity of referral (94.8%, P=0.58). Compared to baseline, post-training evaluation showed a significant reduction of benign lesions sent to dermatologist: the percentage lowered from 52.1 to 35.8% (P=0.0014) for melanocytic nevi and from 38.6 to 17.5% (P<0.001) for benign non-melanocytic lesions (pigmented seborrheic keratoses, dermatofibromas, and vascular lesions). Grouping these two diagnostic categories, the overall specificity in dermatology referral increased from 55.0% at baseline to 73.1% after training (P<0.001). In conclusion, attendance at a 4-h formal training session was able to increase the specificity of family doctors as to dermatologist referral of suspicious lesions (less false-positive referral of benign lesions) without significant loss in sensitivity concerning melanoma.     

Therapeutic studies in NZB/W mice. I. Synergy of azathioprine,cyclophosphamide and methylprednisolone in combination

This study compares different immunosuppressive regimens in the treatment of the lupus-like nephritis of NZB/W mice. Groups of 5-month-old female NZB/W mice were given azathioprine, cyclophosphamide and methylprednisolone in all one-, two- and three-drug regimens, each drug in the relatively low dose of 1.5 mg/kg/day. Treatment for 3 months with one or two drugs resulted in modest suppression of NZB/W disease. Mice receiving all three drugs had significantly less proteinuria, lower titers of anti-DNA antibody and less severe, histologically evident renal involvement than mice treated with one or two drugs. Survival at 1 year was 10% for untreated controls, 44% for one-drug-treated, 37% for two-drug-treated and 86% for the three-drug-treated mice. The survival for the three-drug regimen was significantly longer than any other group (P < 0.01). The three-drug regimen was synergistic, since mice treated with each drug at three times the dose had significantly more proteinuria after 3 months of treatment and lowered 1 year survival (33%). The beneficial effects of triple-drug therapy were attained without increased toxicity. This study represents the first controlled evaluation of single versus combination therapy in a model of autoimmune disease. Based on these results, a controlled evaluation of triple-drug therapy in human systemic lupus erythematosus appears warranted.     

Systematic review of existing guidelines for NAFLD assessment

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis an...     

Fatal Ingestion of Plastic Resin Catalyst

A 46-year-old man ingested approximately 50 ml of a plastic resin catalyst He developed persistent gastrointestinal bleeding, renal and hepatic failure, pneumonitis, and septicemia, and died four weeks later. Autopsy revealed chronic esophagitis and gastritis with massive intraluminal gastrointestinal hemorrhage. This case emphasizes the potential danger of ingestion of such substances.     

Retinal Laser Damage Thresholds as a Function of Image Diameter

The eyes of rhesus monkeys were exposed to argon (514.5 nm) and ruby (694.3 nm) laser irradiation using various retinal image diameters which were estimated by microphotometric techniques. The experimental design for both wavelengths produced image diameters of 40μ to 50μ for the “minimal” case and approximately 500μ to 1,000μ for the larger irradiance series employed. Extramacular retinal exposure sites were examined by ophthalmoscopic and histopathological techniques. Flat preparations of the pigmented epithelium and sensory layers of the retina were utilized in the confirmation of damage at low power levels. All data were statistically analyzed to establish trends, and results were compared for the wavelengths employed. Results indicate that retinal damage is primarily dependent on energy distribution as a function of image diameter and exposure duration.