Cystamine Preparations Exhibit Anticoagulant Activity

Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl)-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination

Clinical pharmacology of antifungal agents to overcome drug resistance in pediatric patients

peer reviewedINTRODUCTION: Antifungal resistance is an emerging problem that increases morbidity and mortality in immunosuppressed pediatric patients, who suffer from invasive fungal diseases. Optimal pharmacological management is critical for the successful treatment of invasive fungal infections by resistant strains. AREAS COVERED: This paper reviews the mechanisms of resistance of different classes of antifungal agents and the current understanding of pediatric antifungal pharmacology for overcoming antifungal resistance in children based on laboratory and clinical studies in the English literature. The therapeutic choices against fungal pathogens with intrinsic or acquired resistance are further reviewed. EXPERT OPINION: There is a paucity of data in the pediatric population regarding the epidemiology of the resistant organisms to different antifungal agents. It is also unknown if there are more prevalent molecular mechanisms that promote antifungal resistance. Selection and dosages of the most effective antifungal agent for overcoming the antifungal resistance is crucial. However, there are limited studies guiding the optimal dosage and duration of treatment for management of emergent antifungal resistance. Further studies are warranted to elucidate the optimal pharmacology of the current antifungal agents against resistant organisms and to advance the development of new antifungal agents

Effects of Parasitic Crustacea on Hosts

This chapter summarises our understanding of the direct effects that parasiticcrustaceans have on their invertebrate and vertebrate hosts. At the individual hostlevel, the effects of infection with parasitic Crustacea with respect to host pathologicalchanges and the development of disease states are reasonably well understood. However,we have a much poorer understanding of how infection affects the physiological,immunological and reproductive status of hosts, with much of what is known arisingfrom studies of sea lice (caligid copepods) infections of salmonids. Quantifyingsublethal impacts of parasitic Crustacea infection on the biology and ecology of hostsis especially challenging even under controlled laboratory conditions. This is due to thecomplex and poorly understood interactions between parasite, host and environmentaldeterminants, which ultimately influence the outcome and magnitude of the effect.There is very limited information on the effects that parasitic Crustacea have on theirhosts at a population level, as well as on the indirect effects that they may have onspecies that interact with their hosts (community level effects). Our relatively goodunderstanding of effects of sea lice on salmonids has been brought about due to thelarge economic impact that these parasites have on farmed salmonids and the necessityto develop new methods for their control. Unfortunately, the progress for other parasitesand hosts is much slower which is in part due to the lack of experimental systems,research tools and funding

Cottoning on to Cotton (Gossypium Spp.) in Arabia and Africa during Antiquity

International audienceThe occurrences of cotton in texts and in the archaeological record (seeds, fibres and textiles) demonstrate the emergence of cotton production centres in north-eastern Africa and western Arabia during the 1st\textendash4th centuries AD, which is concurrent with an increase of cotton trade. These finds could correspond to any of the two Old World domestic cotton species: Gossypium arboreum L., probably domesticated in the Indus valley and traded since the 3rd millennium BC, or Gossypium herbaceum L., an African species about which very little is known, beside its presence in Nubia during Antiquity. Our paper reviews the archaeobotanical, textile and textual data from north-eastern Africa and western Arabia, with specific attention to several sites located in Central Sudan (Muweis), Lower Nubia (Qasr Ibrim), western Egypt (Kellis, Amheida) and north-western Arabia (Madâ'in Sâlih/Hegra). The intention of this review is to a) document how cotton production was integrated into agrarian and trade economies and b) examine current hypotheses regarding the diachronic distribution of the two species. The results highlight the importance of cotton in different agrosystems from the 1st\textendash2nd centuries AD. In Central Sudan, Nubia and Dakhleh oasis, cotton cultivation appeared together with other new tropical/sub-tropical crops, such as sorghum ( Sorghum bicolor) and pearl millet (Pennisetum glaucum subsp. glaucum). This was not the case in north-western Arabia. It seems that cotton production occurred at first as small-scale experiments before scaling up during the 3rd century AD, in conjunction with the spread of the water-wheel in the Nile valley. Cotton in Nubia, and possibly in other neighbouring areas, probably belonged to the African species G. herbaceum, which was in all likelihood domesticated in southern regions, perhaps Ethiopia. We suggest that the increase of exchanges across the Indian Ocean during Antiquity created a favourable context for the emergence of cotton production and its relative expansion before the Islamic period