Biomedical subjects

E W Wolf

Publications and source records attributed to E W Wolf.

16 recordsLinked to original sources

PubMed1998

Responses of human basilar and other isolated arteries to novel nitric oxide donors.

The adducts of nitric oxide (NO), diethylamine/NO (DEA/NO) and diethylenetriamine/NO (DETA/NO), are new NO donors that spontaneously release NO in aqueous solutions. These donors may have therapeutic advantages over sodium nitroprusside (SNP), which depends on metabolism to yield NO. This study was performed to define and compare the pharmacodynamic properties of these NO donors on isolated rings of human, canine, and porcine basilar arteries and further to compare canine and porcine common carotid arteries precontracted with KCl. The median effective concentration (EC50) and the basic effect of 100 microM were determined for each NO donor. On basilar arteries, DEA/NO was the most potent but the maximal dilatation produced by 100 microM did not persist for 60 min, whereas that of DETA/NO and SNP did. DETA/NO was more potent than SNP on all three species of basilar arteries but was the least potent on peripheral (carotid) arteries. Methylene blue in equimolar concentrations significantly inhibited the vasorelaxant effects of DEA/NO and DETA/NO, suggesting a common mechanism of action. Of the NO donors studied, the pharmacodynamic properties of DETA/NO seemed most relevant clinically as a cerebrovascular dilator in being more potent than SNP while producing sustained vasorelaxation.

Animals↗

PubMed1998

Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor.

OBJECT: Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen++ +-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). METHODS: The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 micromol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 micromol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 micromol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-micromol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8. The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 micromol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen. CONCLUSIONS: This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

Analysis of Variance↗

PubMed1996

Morphological differentiation of N1E-115 neuroblastoma cells by dimethyl sulfoxide activation of lipid second messengers.

Quantitative changes in the lipid second messenger diacylglycerol (DAG) were studied in the rat neuroblastoma N1E-115 following exposure to the differentiating agent dimethylsulfoxide (DMSO). Relatively high basal levels of DAG are present in these cells, and addition of 2% DMSO elicited a biphasic increase in DAG levels, dependent on the presence of extracellular Ca2+. Exposure to DMSO also elicited a rapid increase in inositol phosphate and a slight increase in phosphatidic acid (PA), trailing that of DAG. The molecular species (MS) of DAG were analyzed. Within 60 s of DMSO application there were transient increases of DAG representative of phosphatidylinositol (PI) hydrolysis. At longer intervals, more DAG originated from phosphatidylcholine. The MS composition of newly formed PA resembled that of PI and native DAG. Inhibition studies indicated that DAG is formed in the DMSO-treated cells by phospholipases C and that PA formed later is a result of DAG phosphorylation and not activity of phospholipase D (PLD). Undifferentiated cells exhibited an active PLD pathway. In contrast, PLD in DMSO-differentiated cells was not active. In examining the involvement of the sphingomyelin pathway, DMSO exposure was found to increase ceramide levels with a concomitant decrease in sphingomyelin. Addition of the exogenous, soluble analog C6-ceramide to undifferentiated cells resulted in dramatic reductions in DAG and PA levels and PLD activity. These results indicate that DMSO treatment inactivates PLD while activating phospholipases C and the sphingomyelin pathway, suggesting a "switch" between signal transduction pathways in the undifferentiated and differentiated states of N1E-115.

Calcium↗

PubMed1994

Osteopetrosis. A case report.

Osteopetrosis congenita is invariably a fatal disease that is diagnosed within the first decade of the child's life. Although some steps have been taken to overcome this disease by bone marrow transplantation, further research is needed to determine the long-term effectiveness of this treatment. Osteopetrosis tarda is often detected as an incidental finding. Many cases are asymptomatic, yet many patients do suffer from general bone pain, infections, and repeated incidents of pathologic fractures. Such cases may present within the bones of the foot. Treatment is directed at addressing the pathology that may have resulted from the disease state. Osteopetrosis tarda, although rare, can affect the foot. Steps toward treatment of the primary disease entity are still being taken; however, recognition and treatment of the pathology is the primary goal in the adequate treatment of these patients.

Adult↗

PubMed1991

Isolated posterior fibular malleolar fracture. Case report and literature review.

The authors describe a case involving an isolated posterior fibular malleolar fracture in an 80-year-old female, which was identified on multiple lateral radiographs of the involved ankle and confirmed by computed tomography. The patient was treated conservatively with 10 weeks of walking cast immobilization, resulting in poorly acceptable radiographic and clinical results. The authors review the anatomy of the area of involvement. A literature review, the clinical case study, and a discussion of the difficulty in evaluation of these types of fibular fractures are presented along with a protocol for the diagnosis and treatment of these fractures.

Aged↗

PubMed1984