Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Localization of tissue transglutaminase in human carotid and coronary artery atherosclerosis: implications for plaque stability and progression

Although atherosclerosis progresses in an indolent state for decades, the rupture of plaques creates acute ischemic syndromes that may culminate in myocardial infarction and stroke. Mechanical forces and matrix metalloproteinase activity initiate plaque rupture, whereas tissue inhibitors of metalloproteinases have an important (albeit indirect) role in plaque stabilization. In this paper, an enzyme that could directly stabilize the plaque is described. Tissue transglutaminase (TG) catalyzes the formation of epsilon(gamma-glutamyl)lysine isopeptide bonds that are resistant to enzymatic, mechanical, and chemical degradation. We performed immunohistochemistry for TG in atherosclerotic human coronary and carotid arteries. TG was most prominent along the luminal endothelium and in the medium of the vessels with a distribution mirroring that of smooth muscle cells. Variable, often prominent, immunoreactivity for TG was also seen in the intima, especially in regions with significant neovascularization. Additionally, TG was detected in fibrous caps and near the "shoulder regions" of some plaques. A monoclonal antibody to the transglutaminase product epsilon(gamma-glutamyl)lysine isopeptide demonstrated co-localization with TG antigen. Transglutaminase activity was found in 6 of 14 coronary artery atherectomy samples. Cross-linking of TG substrates such as fibrinogen, fibronectin, vitronectin, collagen type I, and protease inhibitors stabilized the plaque. Furthermore, the activation of transforming growth factor-beta-1 by TG might be an additional mechanism for the promotion of plaque stabilization and progression by increasing the synthesis of extracellular matrix components.     

Use of nicardipine during pheochromocytoma removal

Key words  nicardipine - pheochromocytoma - hemodynamic and hormonal change     

Percutaneous gastrostomy tube placement in patients with ventriculoperitoneal shunts

Objective. The purpose of this study is to determine the risk of CNS and/or peritoneal infection in children with ventriculoperitoneal shunts in whom a percutaneous gastrostomy tube is placed. Materials and methods. We placed 205 gastrostomy or gastrojejunostomy tubes from January of 1991 to December 1996. Twenty-three patients (10 boys, 13 girls) had ventriculoperitoneal shunts at the time of placement. All shunts were placed at least 1 month prior to placement of the gastrostomy tube. The patients ranged in age from 8 months to 16 years with a mean age of 6 years, 9 months. Patient weight ranged from 2 kg to 60 kg. All 23 children required long-term nutritional support due to severe neurologic impairment. No prophylactic antibiotics were given prior to the procedure. Of the patients, 21/23 had a 14-F Sacks-Vine gastrostomy tube with a fixed terminal retention device inserted, using percutaneous fluoroscopic antegrade technique. Two of the 23 patients had a Ross 14-F Flexi-flo gastrostomy tube which required a retrograde technique due to a small caliber esophagus in these children. Results. All 23 children had technically successful placements of percutaneous gastrostomy (7) or gastrojejunostomy (16) tubes. Of the children, 21/23 (91 %) had no complications from the procedure. Two of 23 (9 %) patients demonstrated signs of peritonitis after placement of their gastrostomy tubes and subsequently had shunt infections. In both, children CSF culture grew gram-positive cocci. The antegrade technique was used in both children who developed peritonitis. Conclusion. Our study indicates children with ventriculoperitoneal shunts who undergo percutaneous gastrostomy are at greater risk for infection and subsequent shunt malfunction. Therefore, we recommend prophylactic antibiotic therapy to cover for skin and oral flora. Received: 5 August 1997 Accepted: 26 December 1997     

Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats

BACKGROUND: Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury. We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats. MATERIALS ANS METHODS: Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood. RESULTS: Arachidonic acid content and LTB(4) generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB(5) generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats. CONCLUSIONS: EPA supplementation depressed arachidonic acid content and LTB(4) generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema.     

Cyclic adenosine-3',5'-monophosphate stimulates the acute release of placental lactogen from human trophoblast cells

cAMP has been shown to be a second messenger in the release of many hormones and other secretory products. To determine whether cAMP also plays a role in the mechanism of release of human placental lactogen (hPL), we examined the effects of (Bu)2cAMP, isobutyl methylxanthine, forskolin, and cholera toxin on the acute release of hPL from an enriched fraction of hPL-producing trophoblast cells. Static cultures of trophoblast cells exposed to (Bu)2cAMP (5 mM) for 2 h released 2.6 times as much hPL as control cells (P less than 0.01) during the first 0.5 h of exposure. The increase in hPL release was followed by a decrease rate of release during the subsequent 1.5 h. Perifused trophoblast cells (1.5 X 10(6) exposed to 5 mM cAMP for 20 min released 3.2 times as much hPL as control cells. The rate of hPL increased markedly during the first 10 min of exposure, rapidly decreased toward control values during the remainder of the exposure period, and then declined to a subnormal rate for the next 30 min before returning to normal to control values. (Bu)2cAMP, however, had no acute effects on the release of human CG or the release of the cytosolic enzymes alkaline phosphatase and lactic dehydrogenase. The phosphodiesterase inhibitors theophylline (5 mM) and isobutyl methylxanthine (0.5 mM) and the adenylate cyclase activators forskolin (5 micrograms/ml) and cholera toxin (25 micrograms/ml) stimulated hPL release by 75-95%. These results strongly suggest that cAMP is a second messenger in the acute release of hPL.