US-guided paraumbilical vein puncture: an adjunct to transjugular intrahepatic portosystemic shunt (TIPS) placement.

Transjugular intrahepatic portosystemic stent-shunt placement has shown great promise as a means of protal decompression in patients with severe portal hypertension. Passage of a needle from the hepatic venous system into the portal venous system during this procedure may be technically difficult; while it would be advantageous to precisely target the portal vein, most methods of localization are themselves technically difficult, risky, or time-consuming. The authors describe a method of localization of the portal vein that, when feasible, appears to be both safe and technically simple. This method involves percutaneous catheterization of a paraumbilical portosystemic collateral vein under sonographic guidance.

Studies on the mechanism of action of A80915A, a semi-naphthoquinone natural product, as an inhibitor of gastric (H(+)-K+)-ATPase.

A semi-naphthoquinone natural product, A80915A, produced by Streptomyces aculeolatus was found to be a potent inhibitor of gastric (H(+)-K+)-ATPase, the enzyme responsible for acid secretion in the stomach. Enzyme activity was measured by potassium-stimulated hydrolysis of ATP or p-nitrophenolphosphate with enzyme prepared from the stomach fundic mucosa of pigs. Concentration-dependent inhibition was observed with an IC50 of about 2-3 microM for both ATPase and p-nitrophenylphosphatase. A Hill plot indicated that the enzyme has two binding sites for A80915A. Inhibition was not affected by the presence of the reducing agent dithiothreitol, indicating a lack of involvement of enzyme sulfhydryl groups. A 30-min incubation of enzyme with increasing drug concentrations followed by a 10-fold dilution did not alter the IC50, indicating that A80915A does not covalently modify the enzyme. Coincubation of enzyme with 3.8 microM A80915A resulted in time-dependent inhibition. The rate of inhibition was slowed significantly by the presence of 20 mM potassium, rubidium and ammonium but not by 20 mM sodium, lithium and choline, or by 40 mM sucrose. The level of inhibition was influenced by the order of addition of potassium and drug to the enzyme. Taken together, these studies indicate that inhibition by A80915A is dependent on the conformation of gastric (H(+)-K+)-ATPase and that potassium slows the rate of inhibition by converting the enzyme to a conformation where the drug binding site is not as accessible. The mode of action of A80915A is distinct from that of two well characterized proton pump inhibitors, omeprazole and SCH 28080.

Symptomatic native arterial occlusions: early experience with "over-the-wire" thrombolysis.

"Over-the-wire" thrombolysis was successfully accomplished in eight patients with symptomatic lower-extremity ischemia. The authors used a 5-F catheter with multiple side holes designed to pulse-spray urokinase directly over the guidance of a 0.035-inch guide wire. The mean occlusion length was 11.5 cm (range, 5-27 cm). Complete thrombolysis was achieved after delivery of a mean of 480,000 IU of urokinase in a mean infusion time of 48 minutes. One embolic complication was successfully treated with the catheter-wire system. No bleeding complications occurred. Over-the-wire thrombolysis is an alternative method of administering urokinase for the treatment of arterial occlusions.

Mechanism of phorbol ester activation of calcium-activated, phospholipid-dependent protein kinase.

Tumor-promoting phorbol esters activated a calcium-activated, phospholipid-dependent protein kinase by direct complexation with this protein kinase and phospholipid in the presence of divalent cations and this complexation was identical to association of kinase/receptor activity with cell membranes. Treatment of isolated mouse spleen lymphocytes with phorbol ester tumor promoters resulted in a rapid shift in the subcellular localization of both the phorbol ester receptor and a calcium-activated, phospholipid-dependent protein kinase activity. Both activities shifted from almost entirely soluble to largely membrane-associated, which is consistent with a single protein possessing both activities. Activation of partially purified kinase/receptor activity by phorbol ester or calcium alone or in combination occurred in parallel to the formation of a complex between the kinase/receptor and phospholipid. Magnesium also was important both for complex formation and for activation of the protein kinase. Although phorbol ester did not appear to affect the affinity of the kinase/receptor for phospholipid, it did increase the extent of formation of a stable complex between the receptor and the phospholipid. These observations support the hypothesis that the cell membrane is the locus of action of both the phorbol esters and the calcium-activated, phospholipid-dependent protein kinase activity.