Arterial pressure suffices to increase liver stiffness

Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis. The effect of vasodilating glycerol trinitrate (GTN) on LS was also studied. Pressures in the abdominal aorta and caval and portal veins were measured in real time with the PowerLab device (AD Instruments, Dunedin, New Zealand). Baseline LS values in all rats (3.8 ± 0.5 kPa, n = 25) did not significantly differ from those in humans. Epinephrine and norepinephrine drastically increased mean arterial pressure (MAP) from 82 to 173 and 156 mmHg. Concomitantly, LS almost doubled from 4 to 8 kPa, while central venous pressure remained unchanged. Likewise, portal pressure only showed a slight and delayed increase. In the TAA-induced fibrosis model, LS increased from 9.5 ± 1.0 to 25.6 ± 14.7 kPa upon epinephrine injection and could efficiently be decreased by GTN. We finally show a direct association in humans in a physiological setting of elevated cardiac output and MAP. During continuous spinning at 200 W, MAP increased from 84 ± 8 to 99 ± 11 mmHg while LS significantly increased from 4.4 ± 1.8 to 6.7 ± 2.1 kPa. In conclusion, our data show that arterial pressure suffices to increase LS. Moreover, lowering MAP efficiently decreases LS in fibrotic livers that are predominantly supplied by arterial blood.

Purification and Characterization of Nitrate Reductase (NAR) from Pseudomonas sp. SH7 Isolate

Sixty five soil samples and fifteen water samples were collected from different places in which previously explosions were occurred in Iraq. Seven isolates showed ability to utilize 0.1mM trinitrotoluene (TNT) and/or 0.2mM glycerol trinitrate (GTN) as a sole carbon and nitrogen source and one of these isolates showed the highest nitrate reduction which was classified and coded as Pseudomonas sp. SH7. The highest nitrate reductase activity extracted by sonication while optimum conditions for enzyme production in minimal media pH 7 containing 0.25mM GTN at 35oC for 3 days under aerobic condition. Nitrate reductase was purified by 40-60% ammonium sulphate, ion exchange and gel filtration. Nitrate reductase molecular weight determined by SDS-PAGE was 115 kD. The characterization of purified enzyme activity and stability was higher at a pH between 6.5-7.5 and. Maximum activity was at 35oC and stable at 30-40oC for 15 min., while for heat sensitivity 100% activity observed at 45oC for 20 min. Treatment with 200 µM azide and 500 µM cyanide inhibited the activity by 76 and 91% respectively.

The Blood-Brain Barrier in Migraine Treatment

Salient aspects of the anatomy and function of the blood-barrier barrier (BBB) are reviewed in relation to migraine pathophysiology and treatment. The main function of the BBB is to limit the access of circulating substances to the neuropile. Smaller lipophilic substances have some access to the central nervous system by diffusion, whereas other substances can cross the BBB by carrier-mediated influx transport, receptor-mediated transcytosis and absorptive-mediated transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment have been examined with the pressurized arteriography method. The drugs, given both luminally and abluminally, provide important notions regarding antimigraine site of action, probably abluminal to the BBB. The problems with the BBB in animal models designed to study the pathophysiology, acute treatment models and preventive treatments are discussed with special emphasize on the triptans and calcitonin gene-related peptide (CGRP). The human experimental headache model, especially the use of glycerol trinitrate (the nitric oxide model), and experiences with CGRP administrations utilize the systemic administration of the agonists with effects on other vascular beds also. We discuss how this can be related to genuine migraine attacks. Our view is that there exists no clear proof of breakdown or leakage of the BBB during migraine attacks, and that antimigraine drugs need to pass the BBB for efficacy.