Pharmacological Aspects of Vipera xantina palestinae Venom

In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation

Tumor interactions with soluble factors and the nervous system

In the genomic era of cancer research, the development of metastases has been attributed to mutations in the tumor that enable the cells to migrate. However, gene analyses revealed that primary tumors and metastases were in some cases genetically identical and the question was raised whether metastasis formation might be an inherent feature of certain tumor cells. In contradiction to this view, the last decade of cancer research has brought to light, that tumor cell migration, similar to leukocyte and fibroblast migration, is a highly regulated process. The nervous system plays an important role in this regulation, at least in two respects: firstly, neurotransmitters are known to regulate the migratory activity of tumor cells, and secondly, nerve fibers are used as routes for perineural invasion. We also summarize here the current knowledge on the innervation of tumors. Such a process might establish a neuro-neoplastic synapse, with the close interaction of tumor cells and nerve cells supporting metastasis formation

The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

Protein kinase C and clostridial neurotoxins affect discrete and related steps in the secretory pathway

1. The effects on catecholamine secretion of activation of protein kinase C and clostridial neurotoxins were examined in digitonin-permeabilized bovine adrenal chromaffin cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44281/1/10571_2004_Article_BF00711564.pd

On the Mathematical Constitution and Explanation of Physical Facts

The mathematical nature of modern physics suggests that mathematics is bound to play some role in explaining physical reality. Yet, there is an ongoing controversy about the prospects of mathematical explanations of physical facts and their nature. A common view has it that mathematics provides a rich and indispensable language for representing physical reality but that, ontologically, physical facts are not mathematical and, accordingly, mathematical facts cannot really explain physical facts. In what follows, I challenge this common view. I argue that, in addition to its representational role, in modern physics mathematics is constitutive of the physical. Granted the mathematical constitution of the physical, I propose an account of explanation in which mathematical frameworks, structures, and facts explain physical facts. In this account, mathematical explanations of physical facts are either species of physical explanations of physical facts in which the mathematical constitution of some physical facts in the explanans are highlighted, or simply explanations in which the mathematical constitution of physical facts are highlighted. In highlighting the mathematical constitution of physical facts, mathematical explanations of physical facts deepen and increase the scope of the understanding of the explained physical facts. I argue that, unlike other accounts of mathematical explanations of physical facts, the proposed account is not subject to the objection that mathematics only represents the physical facts that actually do the explanation. I conclude by briefly considering the implications that the mathematical constitution of the physical has for the question of the unreasonable effectiveness of the use of mathematics in physics