Blueberry flavonoids inhibit matrix metalloproteinase activity in DU145 human prostate cancer cells.

Regulation of the matrix metalloproteinases (MMPs), the major mediators of extracellular matrix (ECM) degradation, is crucial to regulate ECM proteolysis, which is important in metastasis. This study examined the effects of 3 flavonoid-enriched fractions (a crude fraction, an anthocyanin-enriched fraction, and a proanthocyanidin-enriched fraction), which were prepared from lowbush blueberries (Vaccinium angustifolium), on MMP activity in DU145 human prostate cancer cells in vitro. Using gelatin gel electrophoresis, MMP activity was evaluated from cells after 24-hr exposure to blueberry fractions. All fractions elicited an ability to decrease the activity of MMP-2 and MMP-9. Of the fractions tested, the proanthocyanidin-enriched fraction was found to be the most effective at inhibiting MMP activity in these cells. No induction of either necrotic or apoptotic cell death was noted in these cells in response to treatment with the blueberry fractions. These findings indicate that flavonoids from blueberry possess the ability to effectively decrease MMP activity, which may decrease overall ECM degradation. This ability may be important in controlling tumor metastasis formation.     

Gastroduodenal ulceration following active immunization with prostaglandin E2 in dogs. Role of gastric acid secretion

In this study we present evidence to suggest that gastroduodenal mucosal defects may occur in gastric fistula dogs actively immunized with PGE2-thyroglobulin conjugate. One of four PGE2-immunized dogs developed a chronic pyloroduodenal ulcer with penetration into the pancreas and the other three had endoscopic evidence of gastric and/or duodenal erosions. In contrast, no gastroduodenal mucosal defects were seen in control dogs immunized with thyroglobulin alone. Occurrence of gastroduodenal ulcers or erosions was temporally related to formation of specific antibody to PGE2 suggesting that PGE2 antibody may be responsible for lesion formation. An increase in gastric acid secretion was not observed in PGE2-immunized dogs. Thus, it is likely that mucosal defects occur as a result of an impairment of PGE2-mediated mucosal defense mechanisms. Since gastroduodenal lesions can be visualized by endoscopy, the dog may prove to be useful in studying the role of endogenous PG in ulcer diseases.     

Atp-activated ionic permeability in smooth muscle cells isolated from the guinea pig urinary bladder

Smooth muscle cells from the guinea pig urinary bladder were investigated by voltage clamping at the plasma membrane and using an intracellular perfusion technique. Applying adenosine triphosphate (ATP) at a concentration greater than 3 × 10^–8 M and at a membrane potential of –100 to –30 mV produced a rise in fast inward transmembrane current. A similar effect was exerted by adenosine diphosphate (ADP) and -, -, and ,-methylene ATP. Application of guanosine triphosphate, inosine triphosphate, adenosine monophosphate (AMP), and adenosine failed to activate this current. It was found that AMP blocks ATP receptors competitively. No pharmacological differences were found between the latter ATP receptors and those of rat sensory neurons. The ATP receptors were rapidly desensitized and recovered their sensitivity to agonists extremely slowly. Speed of desensitization was reduced by a decrease in ATP concentration.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 1, pp. 95–100, January–February, 1987.     

Additive and independent responses in a single receptor: aspartate and maltose stimuli on the tar protein

The aspartate and maltose responses of E. coli are mediated through a single membrane receptor, yet the responses are independent and additive. Both stimuli cause methylation of the same 4 glutamic acid residues. More extensive methylation occurs when a cell that has adapted to one stimulus is exposed to the second, or when both stimuli are added simultaneously. The degree of methylation, as well as receptor migration on two-dimensional gels, demonstrates that only one type of protein is involved, rather than two different receptors arising from differential processing of a single gene. A conformational "push-pull" mechanism in which binding of stimulus and covalent modification, producing opposing stresses, can explain these diverse results.     

Fibronectin-degrading proteases from the membranes of transformed cells

The local degradation of fibronectin substrata by Rous sarcoma virus-transformed chick embryonic fibroblasts requires cell-contact-related metalloendoprotease and serine-protease activities. Using fibronectin-containing SDS gels, two large proteases with apparent molecular weights of 120K and 150K were found only in the membrane fraction of transformed cells and were absent in normal cells. Both 120K and 150K proteases were active at neutral pH, but showed preferential inhibitor sensitivities of serine and metal proteases, respectively. The 150K protease appeared to account for most of the proteolytic activity since metalloendoprotease inhibitors completely blocked proteolytic activity of the 150K in fibronectin gels, more than 80% of the fibronectin-degrading activity of solubilized membranes, and largely suppressed the appearance of fibronectin degradation spots in cultures of transformed cells.     

Vaginal treatment with a prostaglandin F2 alpha derivative (alfaprostol) for inducing labor in pregnancy at term

The effectiveness and acceptability of Alfaprostol (an analog of PGF2 alpha) in inducing labor were assessed in 20 pregnant women at term. All subjects had no spontaneous uterine activity before treatment and the mean (M +/- SE) Bishop score was 2.45 +/- 0.21. The drug was administered by vaginal route at the dose of 10 mg every 3 hours. Regular uterine contractions appeared in all patients and delivery occurred in 85% of the patients after a mean time of 9h50min +/- 0h55min following the start of treatment. The mean dose of Alfaprostol utilized to achieve delivery was 29.4 +/- 2.0 mg. No major side effects were noted in the mothers and their fetuses at any time during treatment. Two patients exhibited vomiting. The Apgar score of all newborns at birth was 8 or more. These results suggest the usefulness of Alfaprostol to induce labor in pregnant women at term, as it has oxytocic activity without adverse effects on either the mother or the fetus.     

Evaluation of the single radial-immunodiffusion assay for measuring the glycoprotein content of rabies vaccines

The glycoprotein content of rabies vaccines containing the Pitman-Moore strain of rabies virus was measured by the single radial immunodiffusion assay and correlated with vaccine potency. The variability of this assay was 6.3% for a single vaccine lot tested over a one-year period. Using sera prepared against rabies virus glycoprotein from different strains of virus, the assay gave different values. These differences could be eliminated by using a homologous vaccine strain as an internal reference. Single radial-immunodiffusion values for Pitman-Moore vaccines correlated with the manufacturers' NIH potency assay, but required a mathematical transformation to convert values from one assay to the other. Single radial-immunodiffusion values for Street Alabama Dufferin and Flury-LEP vaccines did not correlate with NIH values. Modification of the single radial immunodiffusion technique and the feasibility of using this assay for the determination of rabies vaccine potency are discussed.     

Short- and long-term effects of proallatotoxin (ethoxyprecocene II) on Rhodnius prolixus females

Oogenesis and oviposition can be inhibited in female of Rhodnius prolixus by means of short-term experiment (first reproductive cycle) of a single dose of ethoxyprecocene II given by ingestion. The inhibition is dose-dependent as measured by oocyte growth, egg maturation and egg deposition. In a long-term experiment (second and third reproductive cycles) egg production and oogenesis can be partially or totally re-established by subsequent blood meals without ethoxyprecocene II. These findings suggest that in female R. prolixus, damage caused to corpus allatum by ethoxyprecocene II, in certain cases, is not irreversible.     

Preparation of scirpentriol and triacetoxyscirpenol in good yield from cultures of Fusarium sambucinum NRRL 13495

Crude extracts of filtrates of cultures of Fusarium sambucinum NRRL 13495 were acetylated or hydrolyzed. After chromatography on cartridge columns of silica gel and recrystallization three times from mixtures of ethyl acetate and hexane, 3,4,15-triacetoxyscirpenol (435 +/- 10 mg/liter of filtrate; mean +/- standard error [n = 3]) and the parent alcohol scirpentriol were isolated (261 +/- 29 mg/liter of filtrate; mean +/- standard error [n = 3]) in 68 and 53% yield for a 130- and 14-fold improvement, respectively, over prior reports.