Isolated stab wound to the artery of Adamkiewicz: case report and review of the literature

Bis(1H-pyrazol-1-yl)- and bis(1H-imidazol-1-yl)pyrimidines were synthesized and evaluated for cytoprotective effects. Among them, 4,6-bis(1H-pyrazol-1-yl)pyrimidine (3) showed a potent inhibitory effect on the HCl.ethanol-, ethanol-, and water immersion stress-induced gastric lesions in rats, and a very low acute toxicity. One of the major factors responsible for the cytoprotective effects of 3 is the increase in the bicarbonate secretion. This compound appears to be a promising cytoprotective drug for the treatment of gastric mucosal ulcers.     

Ischemia and reperfusion in pancreas

Ischemic diseases of heart and brain are the primary causes of mortality in industrialized nations. The ischemic injury with the consecutive reperfusion is responsible for the disturbance of microcirculation with ensuing tissue damage and organ dysfunction. Recent evidence suggests that oxygen-derived free radicals and activated polymorphonuclear leukocytes produced in ischemic tissue are instrumental in the development of ischemic cell injury. In pancreas, ischemia/ reperfusion is proposed as a potentially damaging factor accounting in part for the pathogenesis of acute pancreatitis. Apart from ischemia/reperfusion injury, the kallikrein-kinin system mediates acute inflammation associated with enhanced capillary permeability and accumulation of polymorphonuclear leukocytes, cardinal features of ischemia/reperfusion injury also in acute pancreatitis. Therefore, it seems reasonable to use bradykinin-antagonists to influence postischemic reperfusion injury of the pancreas. In the following, we describe the pathophysiology of ischemia/reperfusion injury with special reference to the pancreatic microcirculation and morphological changes as observed in a model of complete and reversible ischemia. Furthermore, we will discuss the effects of two bradykinin-antagonists (HOE 140 and CP-0597) on functional integrity of the pancreas after ischemia/ reperfusion.     

Behavioral and biomedical research: a partnership for better health

In the last decade, global use of contraceptive methods has increased. About 50% of couples of childbearing age use a modern contraceptive method. This evolution and a positive change in attitude towards male contraception has encouraged research in fertility regulation to enlarge and to improve acceptance of the contraceptive mix. Current injectable contraceptives interfere with the menstrual cycle. Research is exploring ways to minimize such secondary effects by reducing the total hormone dose and by changing the way the active product is delivered (e.g., microspheres). An injectable prototype is an analogue of levonorgestrel (HRP 002). A new IUD is made of leather suspended by a nylon suture which has been inserted into the uterine muscle. RU-486, often used to interrupt early pregnancy, is being tested as an oral contraceptive (OC). It inhibits secretion of gonadotropins and ovulation. It holds promise as an OC with no estrogen component. Since it also inhibits endometrial development and thus prevents implantation, it may someday be used for emergency contraception (i.e., postcoital contraception). New contraceptive implants under study include Norplant RII (2 rods of levonorgestrel lasting for 3 years), Implanon (desogestrel), and Capranor (biodegradable implant lasting 2 years). The female condom consists of a flexible polyurethane sheath with a flexible ring at each end. It has the potential to protect against sexually transmitted diseases since it covers the labial lips and is impermeable to HIV. France and Switzerland have both approved its use. It will enter the UK market at the end of the year. Approval for marketing has been sought in the US.     

Structural model of the outer vestibule and selectivity filter of the Shaker voltage-gated K+ channel

A new generation of structural models were developed of the outer vestibule and ion-selective portion of the voltage-gated Shaker K+ channel. Some features of these models are similar to those that we have developed previously [Durrel S. R. and Guy H. R. (1992) Biophys. J. 62, 238-250; Guy H. R. (1990) In Monovalent Cations in Biological Systems (Pasternak C. A., Ed.), pp. 31-58, CRC Press, Boca Raton, FL; Guy H. R. and Durell S. R. (1994) In Molecular Evolution of Physiological processes (Fambrough D., Ed.), pp. 197-212, The Rockefeller University Press, NY; Guy H. R. and Durell S. R. (1995) In Ion Channels and Genetic Diseases (Dawson D., Ed.), pp. 1-16, The Rockefeller University Press, NY] and other features were modified to make the models more consistent with recent experimental findings. The first part of the P segment is postulated, as always, to form a short alpha helix that spans only the outer portion of the membrane. The helix is tilted so that its C-terminal is nearer the pore than its N-terminal. The latter part of the P segment, P2, is postulated to have a relatively elongated conformation that is positioned approximately parallel to the axis of the pore. Four of the P2 segments assemble to form an ion-selective region that has two narrow regions; one formed by the Y445 side-chains at the outer entrance of the pore and one formed by the backbone of the T442 residues near the innermost part of the P segments. The S6 segment is postulated to form two alpha helices. The first S6 helix packs next to the P segments in our models. The NMR structures of two scorpion toxins, charybdotoxin and agitoxin 2, have been docked into the models of the outer vestibules. The shape of the outer vestibule has been modeled so that specific toxin-channel residue-residue interactions correspond to those that have been identified experimentally.     

Vibrio cholerae Hcp, a secreted protein coregulated with HlyA

Hcp is a 28-kDa secreted protein of Vibrio cholerae regulated coordinately with the hemolysin, HlyA. Both proteins show a dependence on HlyU for expression, suggesting that Hcp may be secreted by V. cholerae in vivo. We have identified and sequenced two genes for Hcp, designated hcpA and hcpB (hemolysin-coregulated protein). The genes encode identical amino acid sequences. Both express a 28-kDa protein, despite open reading frames with only a 19-kDa capacity, suggesting that the Hcp protein runs aberrantly on polyacrylamide gel electrophoresis. There is no cleavage involved in secretion of Hcp from the cell, suggesting a novel mechanism of secretion. An hcp null mutant was constructed, and this strain displayed no deficiency in virulence or colonization in the infant mouse cholera model. From sequence data and primer extension analysis, we predict that the hcp promoter is the sigma 54 type, with a candidate integration host factor binding site upstream. Although hcp and hlyA are coregulated by HlyU, there are no obvious similarities between their promoters. We predict that an intermediate regulator may be involved in the activation of hcp by HlyU. This raises the possibility that HlyU is part of a regulatory cascade.     

ECAT ART - a continuously rotating PET camera: performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department

The past decade has been characterized by few advances regarding the pathophysiology and prevention but many changes in the clinical treatment of patients with preeclampsia. Specifically, recommendations have been made for home or day-care management of a select group of patients with mild gestational hypertension or preeclampsia. Moreover, three randomized clinical trials revealed that expectant management with close monitoring of maternal and fetal conditions is possible in a select group of patients with severe preeclampsia at less than 34 weeks' gestation. In addition, the efficacy of magnesium sulfate in the prevention and control of eclamptic convulsion has been validated in randomized controlled trials performed worldwide. In contrast, recent randomized trials failed to demonstrate any major benefit from the routine use of low-dose aspirin in pregnancy, whereas a recent meta-analysis found calcium supplementation during pregnancy to be effective in reducing the risk of hypertension.