The Chemical Protecting Group Concept Applied in Crosslinking of Natural Tissues with Glutaraldehyde Acetals

This work describes the results of the controlled crosslinking of collagen matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde acetals and lysine protonation due to the acidic conditions of acetal formation. Materials crosslinked by this approach were characterized by thermal stability comparable to those obtained by conventional procedures with mechanical properties expected for bioprosthesis manufacture and with a higher stability toward collagenase hydrolysis. The integrity of the microfibrillar structure was confirmed by optical and scanning electronic microscopy. The results indicate that the glutaraldehyde acetals procedure may be of potential use for the crosslinking of bovine pericardium used in the manufacture of bioprosthetic devices. Advantages may be related to the production of materials with homogeneous crosslinking distributions, associated with better definition in the nature of the chemical link that they introduce, due to a better distribution of glutaraldehyde within the tissue matrix before the crosslinking reaction is allowed to occur. As a result, materials with improved biological and mechanical properties are expected.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

Ganglioside-induced enhancement of behavioral recovery after bilateral lesions of the entorhinal cortex

Previous research has shown that exogenous gangliosides improve recovery of learned alternation after unilateral lesions of the entorhinal cortex. Since this recovery is thought to depend upon axonal sprouting, it has been hypothesized that ganglioside-induced improvement may be due to enhanced sprouting. The present study examined the effects of ganglioside treatments on learned alternation after bilateral entorhinal lesions. Whereas control rats exhibited a severe impairment postoperatively, ganglioside-treated (50 mg/kg total brain gangliosides; i.m.) rats committed significantly fewer errors and perseverative errors, and reached criterion sooner. The two groups exhibited comparable rates of daily improvement in performance. Since bilateral entorhinal lesions preclude the sprouting which is important for recovery of alternation, the ganglioside-induced improvement observed in the present study appears to be independent of sprouting.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

Use of Cyclooxygenase Inhibitors and Risk of Melanoma in High-Risk Patients

Background Results from in vitro and animal studies suggest that cyclooxygenase (COX) inhibitors may reduce the risk of melanoma, but among humans, the evidence remains limited.
Objective In a pilot retrospective cohort, to determine the relationship between the use of COX inhibitors and the incidence, recurrence, and metastases of melanoma in high-risk patients.
Methods Reviewing computerized records at the Miami Veterans Affairs Medical Center, we retrospectively examined the association between COX inhibitor use and melanoma incidence, recurrence, and metastases in high-risk subjects: white subjects previously diagnosed with melanoma (1996–2003). We evaluated three potential outcomes: new melanoma diagnosis, recurrence of a previous melanoma, and melanoma metastasis.
Results Eighty-three subjects with melanoma were included. There was one metastasis among 28 subjects prescribed COX inhibitors, whereas four new melanomas (7.3%), two melanoma recurrences, and six metastases (10.9%) occurred among 55 patients not prescribed COX inhibitors. Although no individual outcomes measures reached statistical significance, combining the three measures, these were significantly lower in users of COX inhibitors compared with nonusers (1 vs 12;  p = .05  ). After adjustment for age and tumor depth of invasion, COX inhibitor users had significantly lower rates of melanoma outcome measures (odds ratio 0.08; 95% confidence interval 0.01–0.77;  p = .03  ).
Conclusion Potential exists for chemoprevention of melanoma among high-risk patients.     

Guidelines for Community-Acquired Pneumonia Within Disease Management Programs

Several national and international organizations have developed and published guidelines for the treatment of patients with community-acquired pneumonia (CAP). Guidelines from Europe, the US, Canada and Latin America classify patients in different groups based on the severity of pneumonia, site of care and presence of risk factors for resistant organisms. The initial antibacterial therapy is designed to cover only the likely organisms able to infect a particular group of patients. An evaluation of current guidelines indicates that there are significant similarities in regard to classification of patients and initial antibacterial therapy. One objective of this review is to present the clinician with a practical approach to antibacterial selection based on current published guidelines for CAP.Although most of the care recommended in guidelines is evidence-based and associated with better clinical outcomes and/or decreased healthcare cost, there is still a significant gap between recommended care and actual care of patients with CAP. Dissemination of guidelines at the local level has proved to have a minimal effect in changing local practices. To bring the local care of patients with CAP closer to the care recommended in guidelines, it is necessary to have an appropriate plan for guideline implementation. This review provides the clinician and other healthcare decision-makers with a methodology for implementation of national guidelines at the local hospital level.