Leishmanial superoxide dismutase: A possible target for chemotherapy

Leishmania tropica promastigotes stimulate macrophages to produce activated oxygen as measured by luminol-enhanced chemiluminescence. Exogenous superoxide dismutase and catalase inhibit this by 95%, implying that both superoxide and hydrogen peroxide are generated. Whereas leishmania have undetectable levels of catalase, and very little glutathione peroxidase, they have relatively high amcunts of superoxide dismutase (23 units/mg protein). The leishmanial superoxide dismutase is cyanide-insensitive but azide- and peroxide-sensitive, suggesting that the enzyme may be iron-containing. Furthermore, the leishmanial superoxide dismutase is insensitive to diethyldithiocarbamate, which inhibits vertebrate enzymes. Thus, leishmania may contain a superoxide dismutase which is different from its host's enzyme. A specific inhibitor of this enzyme might serve as an antileishmanial agent.     

Early steps of picornavirus infection

Picornaviridae is a large family of viruses that cause a variety of infectious diseases in humans and animals. It includes important viruses such as poliovirus, hepatisis A virus and foot and mouth disease virus. Early steps of infection play important roles in determining the host range and the target organs for each virus. Here, I review the recent advances in the studies of cellular receptors for picornaviruses, mechanisms of cell entry and viral uncoating.     

Cell biology: watching the first steps of podosome formation

Podosomes and invadopodia are actin-rich structures that have come under intense scrutiny over the past several years due to their critical roles in cell migration and invasion. Examination of the initial stages of podosome formation has revealed an important role for the phosphoinositide PI(3,4)P(2) in anchoring the scaffold protein Tks5 to the plasma membrane.     

The first steps of transposable elements invasion: parasitic strategy vs. genetic drift

Transposable elements are often considered as selfish DNA sequences able to invade the genome of their host species. Their evolutive dynamics are complex, due to the interaction between their intrinsic amplification capacity, selection at the host level, transposition regulation, and genetic drift. Here, we propose modeling the first steps of TE invasion, i.e., just after a horizontal transfer, when a single copy is present in the genome of one individual. If the element has a constant transposition rate, it will disappear in most cases: the elements with low-transposition rate are frequently lost through genetic drift, while those with high-transposition rate may amplify, leading to the sterility of their host. Elements whose transposition rate is regulated are able to successfully invade the populations, thanks to an initial transposition burst followed by a strong limitation of their activity. Self-regulation or hybrid dysgenesis may thus represent some genome-invasion parasitic strategies.     

Toxoplasma gondii infection in horses. A review

This review updates those written by Dubey and Beattie in 1988 (1988a) and by Tenter et al in 2000, on pathological and epidemiological aspects of Toxoplasma infection in horses. Under natural conditions, seroprevalence may variate from 0% up to 90%. This wide variation may be due to the sensitivity of the serological methods, to the age of animals, to the geographical area, and even to the hygienic condition of the farms and farm management. With few exceptions, horses are considered one of the less sensitive specie to the pathogenic effect of Toxoplasma gondii. In fact, neither under experimental nor under natural condition a genuine pathologic picture related to the toxoplasmic infection has been described. In one occasion the organism has been isolated from an eye condition and in others a connection between a higher frequency of unspecified pathological conditions and a positive response to serological test for Toxoplasma has been speculated. Diaplacental transmission and the following abortion have been only occasionally reported, and at least in one case in a quite trustworthy way, therefore it must be considered possible, though rare. Although infection of humans due to the consumption of horse meat has never been reported, the existence of a possible risk arouses by the demonstration of the presence of parasite stages in either naturally or experimentally infected horses, which resulted to be infective for mice and/or cats.     

The first steps towards hearing: mechanisms of otic placode induction

The entire inner ear, together with the neurons that innervate it, derive from a simple piece of ectoderm on the side of the embryonic head the otic placode. In this review, we describe the current state of the field of otic placode induction. Several lines of evidence suggest that all craniofacial sensory organs, including the inner ear, derive from a common "pre-placodal region" early in development. We review data showing that assumption of a pre-placodal cell state correlates with the competence of embryonic ectoderm to respond to otic placode inducing signals, such as members of the fibroblast growth factor (FGF) family. We also review evidence for FGF-independent signals that contribute to the induction of the otic placode. Finally, we review recent evidence suggesting that Wnt signals may act after FGF signaling to mediate a cell fate decision between otic placode and epidermis.     

NMR spectroscopic analysis of the first two steps of the pentose-phosphate pathway elucidates the role of 6-phosphogluconolactonase.

The pentose-phosphate pathway provides reductive power and nucleotide precursors to the cell through oxidative and nonoxidative branches, respectively. 6-Phosphogluconolactonase is the second enzyme of the oxidative branch and catalyzes the hydrolysis of 6-phosphogluconolactones, the products of glucose 6-phosphate oxidation by glucose-6-phosphate dehydrogenase. The role of 6-phosphogluconolactonase was still questionable, because 6-phosphogluconolactones were believed to undergo rapid spontaneous hydrolysis. In this work, nuclear magnetic resonance spectroscopy was used to characterize the chemical scheme and kinetic features of the oxidative branch. We show that 6-phosphogluconolactones have in fact a nonnegligible lifetime and are highly electrophilic compounds. The delta form (1-5) of the lactone is the only product of glucose 6-phosphate oxidation. Subsequently, it leads to the gamma form (1-4) by intramolecular rearrangement. However, only the delta form undergoes spontaneous hydrolysis, the gamma form being a "dead end" of this branch. The delta form is the only substrate for 6-phosphogluconolactonase. Therefore, 6-phosphogluconolactonase activity accelerates hydrolysis of the delta form, thus preventing its conversion into the gamma form. Furthermore, 6-phosphogluconolactonase guards against the accumulation of delta-6-phosphogluconolactone, which may be toxic through its reaction with endogenous cellular nucleophiles. Finally, the difference between activity of human, Trypanosoma brucei, and Plasmodium falciparum 6-phosphogluconolactonases is reported and discussed.     

Post-stroke infection: A systematic review and meta-analysis

Background  

stroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.     

Parasitic infection of the bovine perinate: A review

Factors affecting the frequency and outcome of infection of the bovine perinate are reviewed in relation to 18 recognized parasitic entities.     

Farnesyltransferase as target for non-cytotoxic anti-cancer agents: first steps]

Farnesylation is a key maturation step involved in the ras-dependent transformation of cells. This acylation step is catalyzed by protein: farnesyltransferase, a soluble enzyme. The present work describes the use of a new HPLC method of measurement of this enzymatic activity using the K-ras-derived CVIM tetrapeptide as substrate. The method is used to check the activity catalyzed by cytosols issued from various types of cancer cells. J82, a human bladder cancer cell line was retained for measurement of the inhibitory potency of a few peptide sequences and will be used as starting biological material for the purification of the enzyme. This HPLC method presented herein has the main advantages over other published methods of being automatisable and versatile, because it can be used with a wide spectrum of peptide substrates. Results presented herein are only first studies and need some more structural observations. The obtention of the cancer cell line-derived, partially purified farnesyltransferase will hopefully lead us to the discovery of specific inhibitors with potential non-cytotoxic anti-cancer activities.     

Polio vaccine: the first 50 years and beyond. Summary of the meeting and next steps.

A conference on "Polio vaccine: the first 50 years and beyond" was held in Toronto, Canada, June 2005. The purpose of the conference was to bring together regulators, manufacturers, academics and public health authorities to celebrate the accomplishments of the past 50 years, to consider the challenges of achieving and sustaining polio eradication and to review standardization and regulatory issues around existing and new polio vaccines. In the final session of the conference the following summary of the meeting was presented.