VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.     

Centurion syndrome. Idiopathic anterior displacement of the medial canthus

Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25-30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor.     

Improved method for harvesting human Schwann cells from mature peripheral nerve and expansion in vitro

The pharmacological profile of a novel dual inhibitor, tepoxalin and of its carboxylic acid metabolite on cyclooxygenase and lipoxygenase pathways was evaluated by in vitro incubation with synovial tissue. Tissue specimens obtained at surgery in rheumatoid arthritis (RA, n = 10) or osteoarthritis (OA, n = 11) patients were incubated. Tepoxalin (10(-7), 10(-6), 10(-5) M) decreased eicosanoid release calculated in % of tyrode control for OA: LTC4 to 71-33%, 6-keto-PGF1a to 37-20%, PGE2 to 29-6%. For RA: LTC4 to 56-22%, 6-keto-PGF1a to 43-22%, PGE2 to 57-32%. Similarly, its metabolite (10(-7), 10(-5)M) decreased release in OA: LTC4 to 99 and 60%, PGE2 to 42 and 20%, 6-keto-PGF1a to 54 and 25%. In RA:LTC4 to 81 and 45%, PGE2 to 61 and 30%, 6-keto-PGF1a to 46 and 18%. Significance (P < 0.05) was achieved for all but 1 group (LTC4 metabolite at 10(-7)M vs tyrode). In summary a marked and dose dependent decrease of LT and PG release was obtained when incubating the dual inhibitor tepoxalin and its active carboxylic acid metabolite with synovial tissue at doses expected to be reached in the joint during therapy.     

Mass customization of medical devices and implants: state of the art and future directions

The medical field is one in which the need for customization can be clear cut, as providing tailored devices and implants for unique physiologies can provide for a better overall treatment than the use of 'off the shelf' devices and implants. Customization in the production of medical products can be roughly divided into consideration of medical devices, and of implantable parts or systems. The present paper outlines the current state of the art in both of these areas, presents details of projects that are ongoing at the University of Leeds and outlines future research directions.     

Nonlinear self-guiding and switching in an all-fiber device

We study the nonlinear propagation of light in optical fibers in the strong nonlinearity limit. In this limit, the transverse guiding properties are altered and cannot be decoupled from the longitudinal part of the wave equation. We consider a refractive index profile with no bound modes at low intensities and show that stable self-guiding occurs at a critical intensity. This critical intensity is a property of the guide and can be made much lower than the threshold for unstable self-focusing. We consider a particular design for which self-guiding occurs at three orders of magnitude lower than the self-focusing threshold.     

Personality and the predisposition to engage in risky or problem behaviors during adolescence.

Longitudinal data from a representative sample of 1,978 Black and White adolescents were used to examine the role of personality in multiple risk or problem behaviors. Results indicate that covariation among diverse behaviors (educational underachievement, delinquent behavior, substance use, sexual behavior) can be adequately modeled by a single higher order factor, and that impulsivity and avoidance coping serve as generalized risk factors for involvement in these behaviors. Whereas none of the personality variables examined explained change in problem behaviors once established, avoidance coping prospectively predicted involvement among a subgroup of adolescents with little or no prior involvement. Results suggest that dysfunctional styles of regulating emotions and emotionally driven behaviors are core features of risky or problem behaviors during adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Obtaining shorter regular expressions from finite-state automata

We consider the use of state elimination to construct shorter regular expressions from finite-state automata (FAs). Although state elimination is an intuitive method for computing regular expressions from FAs, the resulting regular expressions are often very long and complicated. We examine the minimization of FAs to obtain shorter expressions first. Then, we introduce vertical chopping based on bridge states and horizontal chopping based on the structural properties of given FAs. We prove that we should not eliminate bridge states until we eliminate all non-bridge states to obtain shorter regular expressions. In addition, we suggest heuristics for state elimination that leads to shorter regular expressions based on vertical chopping and horizontal chopping.