The analgesic activity of crotamine, a neurotoxin from Crotalus durissus terrificus (South American rattlesnake) venom: a biochemical and pharmacological study

Crotamine, a 4.88 kDa neurotoxic protein, has been purified to apparent homogeneity from Crotalus durissus venom by gel filtration on Sephadex G-75. When injected (i.p. or s.c.) in adult male Swiss mice (20-25 g), it induced a time-dose dependent analgesic effect which was inhibited by naloxone, thus suggesting an opioid action mechanism. When compared with morphine (4 mg/kg), crotamine, even in extremely low doses (133.4 microg/kg, i.p., about 0.4% of a LD50 is approximately 30-fold more potent than morphine (w/w) as an analgesic. On a molar basis it is more than 500-fold more potent than morphine. It is also much more potent than the lower molecular weight crude fractions of the same venom. The antinociceptive effects of crotamine and morphine were assayed by the hot plate test and by the acetic acid-induced writhing method. Therefore, both central and peripheral mechanisms should be involved. Histopathological analysis of the brain, liver, skeletal muscles, stomach, lungs, spleen, heart, kidneys and small intestine of the crotamine injected mice did not show any visible lesion in any of these organs by light microscopy. Since crotamine accounted for 22% (w/w) of the desiccated venom, it was identified as its major antinociceptive low molecular weight peptide component.     

4-hydroxynonenal specifically inhibits c-myb but does not affect c-fos expressions in HL-60 cells

4-Hydroxynonenal, an aldehyde produced from lipid peroxidation of cellular membranes, inhibits growth and induces differentiation of HL-60 human leukemic cell line. Since it is highly unstable in the culture medium, its effectiveness is increased when added repeatedly to the cell suspension. We have previously demonstrated that HNE inhibits c-myc but not N-ras expression in HL-60 cells. Here we investigate its effect on the expression of c-myb and c-fos, two early genes involved in the induction of myeloid and monocytic differentiation. Moreover, since c-fos is directly correlated with the intracellular level of cAMP, we also analysed the cAMP concentration after aldehyde treatment. HNE significantly inhibits c-myb expression during and after repeated treatments. A single administration of 1 microM HNE decreases c-myb mRNA at 1 hour whereas 10 microM HNE inhibits c-myb expression from 3 to 6 hours after treatment, and then the expression returns to the control level. By contrast, c-fos expression and intracellular cAMP concentration do not show any significant change after HNE treatments.     

Current aspects of creation of expert systems in aviation medicine

Topical directions of developing the medical expert systems (MES) are considered. The problems to be solved by using programming and informational means as part of MES are discussed. A classification of the knowledge of expert physicians who directly deal with decision making is proposed. The characteristics of the developed MES well appreciated by the results of their operation are given. They show new trends associated with the update of medical knowledge and the developmental level of information technologies.     

Trends in the management of truncal valve insufficiency

Expression of c-fos-like immunoreactivity has been used as a marker for neuronal activation and is elevated in the periaqueductal gray following stressful and noxious stimuli, and opioid withdrawal. The present study examined the staining of c-fos-like immunoreactivity following opiate withdrawal or swim-stress (2.5-3 min at 21 degrees C) in periaqueductal gray neurons of the rat which had projections to and through the rostral ventromedial medulla identified by microinjection of the retrograde tracer, Fast Blue, into the nucleus raphe magnus prior to development of morphine dependence. Both naloxone-precipitated withdrawal and swim-stress increased numbers of neurons expressing c-fos-like immunoreactivity in periaqueductal gray. Naloxone-precipitated withdrawal did not increase the number of double-labelled neurons in periaqueductal gray suggesting that neurons excited during opioid withdrawal do not project to the ventromedial medulla. In contrast, swim-stress produced increases in double-labelled neurons in periaqueductal gray suggesting that many periaqueductal gray neurons activated by swim-stress project to the ventromedial medulla. These findings suggest that naloxone-precipitated withdrawal does not activate ventrolateral periaqueductal gray neurons which are involved in descending inhibitory pathways, consistent with behavioural observations that naloxone-precipitated withdrawal is qualitatively opposite to electrical and chemical stimulation of the ventrolateral periaqueductal gray. The results are also consistent with a role of descending projections from periaqueductal gray in stress-induced antinociception.     

Study of the browning and gelation kinetics in a concentrated sheep milk and sucrose system

Browning and gelation kinetics of a sheep milk and sucrose model system with 70% total solids (simulating dulce de leche) and the influence of temperature and sucrose content on this process were studied. The Kubelka–Munk index and subjective heat stability tests were used to monitor nonenzymatic browning and to determine gelation time. Browning and gelation processes showed different kinetics where gelation was shown to occur much faster than browning. Both independent variables (temperature and sucrose content) had a significant influence in both processes, where temperature had the higher impact.     

Ethanolic extraction of sunflower oil in a pulsing extractor

Oil extraction by ethanol from partially defatted prepressed sunflower seeds in pulsed and nonpulsed extractors was compared. The oil yield was increased by 8.7% after short extraction periods (up to 6.06 residence times) with a pulsing flow, which was probably due to reduction in the axial dispersion that induces a greater concentration gradient between the miscella surrounding the solid and the bulk miscella.     

Comparison between the conventional anaerobic digestion of sewage sludge and its combination with a chemical or thermal pre-treatment concerning the removal of pharmaceuticals and personal care products.

Many novel treatment technologies, usually representing a pre-treatment prior to the biological degradation process, have been developed in order to improve the recycling and reuse of sewage sludge. Among all the methods available, a chemical (alkaline) and a thermal treatment have been considered in this study. The behaviour of 13 substances belonging to different therapeutic classes (musks, tranquillisers, antiepileptic, anti-inflammatories, antibiotics, X-ray contrast media and estrogens) has been studied during the anaerobic digestion of sewage sludge combined with these pre-treatments (advanced operation) in comparison with the conventional process. Two parameters have been analysed: the temperature (mesophilic and thermophilic conditions) and the sludge retention time. While organic matter solubilization was higher with the alkaline process (55-80%), no difference between both pre-treatments was observed concerning volatile solids solubilization (up to 20%). The removal efficiencies of solids and organic matter during anaerobic digestion ranged from 40-70% and 45-75%, respectively. The higher removal efficiencies of pharmaceuticals and personal care products were achieved for the antibiotics, Naproxen and the natural estrogens (>80%). For the other compounds, the values were in the range 20-70%, except for Carbamazepine, which was not removed at any condition tested.