Becaplermin

Becaplermin is a recombinant human platelet-derived growth factor B-chain homodimer (rh-PDGF-BB) for topical treatment of full-thickness diabetic neuropathic ulcers and pressure ulcers. rh-PDGF-BB promotes wound healing, probably by increasing granulation tissue formation via increased migration and proliferation of cells, with subsequent extracellular matrix deposition. Accelerated healing has been demonstrated in healthy and healing-impaired animals and in patients with lower extremity diabetic neuropathic ulcers and pressure ulcers. Pharmacokinetic studies in humans have shown that systemic absorption of becaplermin after topical administration to ulcers is minimal. A clinical trial in patients with stage III or IV diabetic neuropathic ulcers of the lower extremities which had adequate perfusion showed that becaplermin 100 microg/g applied once daily in conjunction with a standardised programme of good wound care significantly increased the proportion of patients with complete healing of the ulcer and reduced the time to complete healing compared with placebo or good wound care alone. Becaplermin was also superior to placebo in patients with pressure sores. Becaplermin was well tolerated in clinical trials and the rate of discontinuation because of adverse events was similar to that among placebo recipients. Rash, which occurred in 2% of becaplermin and 2% of placebo recipients, may be attributable to the vehicle used.     

Antimycobacterial activities of oxazolidinones: a review

Oxazolidinones are a new class of totally synthetic antibacterial agents with wide spectrum of activity against a variety of clinically significant susceptible and resistant bacteria. These compounds have been shown to inhibit translation at the initiation phase of protein synthesis. DuP-721, the first oxazolidinone showed good activity against M. tuberculosis when given orally or parenterally to experimental animals but was not developed further due to lethal toxicity in animal models. Later two oxazolidinones, PNU-100480 and Linezolid, demonstrated promising antimycobacterial activities in the murine model. While Linezolid has been approved for clinical use, PNU-100480 was not been developed further. DA-7867 showed good in vitro and better in vivo efficacy than Linezolid but was poorly tolerated in rat toxicology studies. The antimycobacterial activity of AZD-2563 has not been explored. RBx 7644 had modest antimycobacterial activity while RBx 8700 has potent antibacterial and concentration dependent activity against all slow growing mycobacteria. It demonstrated better activity than RBx 7644 against MDR strains of M. tuberculosis along with intracellular activity. Toxicity, especially myelosuppression, has been an important limiting factor for development of an oxazolidinones. The GM-CSF assay has helped in selecting molecules with less myleosuppressive potential. We report, a review on the promising antituberculosis activities of the class oxazolidinones.     

Toxicity of ambient atmospheric particulate matter from the Lake Michigan (USA) airshed to aquatic organisms

Short-term chronic and acute aquatic bioassays are valuable tools in screening a variety of environmental samples. However, only a limited number of studies have used these methods for testing the toxicity of atmospheric particulate matter samples. Previous studies have shown that compounds known to have adverse biological effects, such as polycyclic aromatic hydrocarbons, are deposited in significant quantities into Lake Michigan (USA); however, these compounds comprise a small portion of the total particulate matter deposition. In the present study, a method is described for using Ceriodaphnia dubia, Selenastrum capricornutum (green algae), and MitoScan bioassays to compare the toxicities of reconstituted hard freshwater and methylene chloride extracts of atmospheric particulate matter collected at three locations around the southern shore of Lake Michigan in August 2000. The locations include an urban/industrial site in Milwaukee (WI, USA), an urban-impacted/industrial site in Porter (IN, USA), and a rural site in Bridgman (MI, USA). The bulk chemistry, including organic and elemental carbon, sulfate, nitrate, ammonium, and chloride, shows regional similarities over the sampling event, but the toxicities vary spatially by site, by extraction solvent, and by bioassay. Thus, the bioassays are sufficiently sensitive to show differences in toxicity among the atmospheric particulate matter extracts and have significantly different responses to the samples to enable an initial comparison of toxicity from the different sites.     

Cyclic sciatica caused by infiltrative endometriosis: MRI findings

Endometriosis, an important gynecological disorder of reproductive women, affects most commonly the ovaries and less frequently the gastrointestinal tract, chest, urinary tract, and soft tissues. Endometriosis classically appears on MRI as a mass with a large cystic component and variable signal intensities on T1- and T2-weighted images due to the presence of variable degradation of hemorrhagic products. Endometriosis in an atypical location, an infiltrative appearance and without cystic-hemorrhagic components has rarely been described. We report on a 33-year-old woman with cyclic sciatica due to histologically documented infiltrative endometriosis involving the area of the left sciatic notch.     

Role of medullary excitatory amino acid receptors in mediating the 10-Hz rhythm in sympathetic nerve discharge of cats

We tested the hypothesis that excitatory amino acid (EAA)-mediated transmission plays a role in generating the 10-Hz rhythm in sympathetic nerve discharge (SND) of baroreceptor-denervated, urethane-anesthetized cats. Microinjection of either an N-methyl-d-aspartate (NMDA) or non-NMDA receptor antagonist into any one of three medullary regions (lateral tegmental field, rostral, or caudal ventrolateral medulla) essentially eliminated the 10-Hz rhythm in inferior cardiac SND. We conclude that EAA receptors in the medulla are critical for generation of the 10-Hz rhythm.     

Quantification of posterior capsular opacification in digital images after cataract surgery

PURPOSE: To describe a software program developed to provide an objective assessment of the amount of posterior capsular opacification (PCO) in high-resolution digital images of the posterior capsule after cataract surgery. METHODS: Images are analyzed by a set protocol of defining the area of the posterior capsule, removing the Purkinje light reflexes by intensity segmentation, contrast enhancement, filtering to enhance low-density PCO, and variance analysis using a co-occurrence matrix to assess texture. The accuracy of the system was tested for validity and repeatability. RESULTS: The software developed has been demonstrated to be an objective method of quantifying PCO. In validation tests, the image analysis-derived measure of PCO showed good agreement with clinically derived measures of PCO. Clinicians assessed PCO on a computer screen image and also under slit lamp examination (Pearson correlation coefficient for both methods >0.92). The entire acquisition and analysis system was demonstrated to have a confidence limit for 2 SDs of 9.8% for group data. CONCLUSIONS: This system is capable of producing an accurate and reproducible measure of PCO that is relevant to assessing techniques of PCO prevention.