Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase.

BACKGROUND AND PURPOSE: Inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of the endogenous cannabinoid (CB) receptor ligand anandamide (AEA), are effective in a number of animal models of pain. Here, we investigated a series of isoflavones with respect to their abilities to inhibit FAAH. EXPERIMENTAL APPROACH: In vitro assays of FAAH activity and affinity for CB receptors were used to characterize key compounds. In vivo assays used were biochemical responses to formalin in anaesthetized mice and the 'tetrad' test for central CB receptor activation. KEY RESULTS: Of the compounds tested, biochanin A was adjudged to be the most promising. Biochanin A inhibited the hydrolysis of 0.5 microM AEA by mouse, rat and human FAAH with IC(50) values of 1.8, 1.4 and 2.4 microM respectively. The compound did not interact to any major extent with CB(1) or CB(2) receptors, nor with FAAH-2. In anaesthetized mice, URB597 (30 microg i.pl.) and biochanin A (100 microg i.pl.) both inhibited the spinal phosphorylation of extracellular signal-regulated kinase produced by the intraplantar injection of formalin. The effects of both compounds were significantly reduced by the CB(1) receptor antagonist/inverse agonist AM251 (30 microg i.pl.). Biochanin A (15 mg.kg(-1) i.v.) did not increase brain AEA concentrations, but produced a modest potentiation of the effects of 10 mg.kg(-1) i.v. AEA in the tetrad test. CONCLUSIONS AND IMPLICATIONS: It is concluded that biochanin A, in addition to its other biochemical properties, inhibits FAAH both in vitro and peripherally in vivo.

Multifetal pregnancy reduction: psychodynamic implications.

New reproductive technologies, such as advanced infertility treatments, may have significant implications for women's psychological experience of pregnancy and motherhood. This paper examines some of the psychodynamic implications of multifetal pregnancy reduction, a medical procedure in which some of the fetuses in a multiple pregnancy are aborted while other fetuses are carried to term. Forty-four women who had undergone pregnancy reductions were interviewed about their emotional experience of this medical intervention and their subsequent pregnancies. A qualitative analysis of their experience was conducted from five psychoanalytically-informed vantage points: drive theory, ego psychology, object relations theory, self psychology and a developmental perspective. Women experienced having to abort some of their fetuses as a stressful and distressing life event, and a fourth of the women experienced bereavement reactions which impaired their functioning for at least two weeks. Conscious and unconscious responses to the procedure included ambivalence, guilt, and a sense of narcissistic injury, increasing the complexity of their attachment to the remaining babies. However, the achievement of the developmental goal of parenting healthy birth children helped most women feel that they had made the right decision for themselves and their families. Further research is indicated, including interviews before the reduction and long-term follow-up of mothers and surviving children.

Comparison of colon cleansing methods in preparation for colonoscopy.

Colonoscopy cleansing regimens were evaluated in 197 patients randomized in two study phases to one of four methods: group 1 (64 patients), 3-day clear liquid diet; group 2 (40 patients), 3-day minimum-residue diet; group 3 (44 patients), 1-day minimum-residue diet; group 4 (49 patients), Golytely. Groups 1-3 also received laxatives and enemas before colonoscopy. Physician assessment by endoscopists unaware of the method of colon cleansing favored group 4 (p less than 0.001), with good to excellent preparations achieved in 69% of group 1, 80% of groups 2 and 3, and 92% of group 4. Group 4 patients also experienced less abdominal distress (p less than 0.01). Breath hydrogen and methane levels were measured in groups 3 and 4 both before and after preparation. The decrease in pre- to postprep levels of hydrogen and methane were not significantly different between the groups and postprep gas concentrations were below combustible levels in both groups. There were no clinically significant differences between the four groups for any of the other measured hematologic or biochemical parameters. It is concluded that Golytely is a safe, effective method of colon cleansing, well tolerated by patients.

Veres needle in the pleural space.

The Veres needle is designed to allow entry into body cavities without trauma to underlying organs. Its major use has been in the induction of a pneumoperitoneum for peritoneoscopy. An initial successful evaluation of its use was in the pleural space of dogs. A subsequent analysis of complications in 69 thoracenteses using the Veres needle and 152 thoracenteses using a conventional needle favored the Veres needle (P = .05). We believe that the Veres needle is a safe and technically superior instrument for thoracentesis and that it deserves further application and study.

Radionuclide esophageal transit: an evaluation of therapy in achalasia.

We measured quantitative esophageal transit, expressed as percentage of esophageal retention, before and after pneumatic dilatation in two patients with achalasia. In the sitting position they ingested a 500 ml liquid meal containing 500 muCi technetium Tc 99m sulfur colloid. Radioactivity counts of the entire esophagus were plotted at five-minute intervals for 30 minutes. In five normal control subjects the esophagus essentially cleared in less than one minute. Both patients with achalasia had definite retention 30 minutes before dilatation and had quantitative improvement after dilatation. Radionuclide scintigraphic esophageal transit probably correlates better than other parameters with the physiologic degree of obstruction in achalasia.

Transluminal expandable nitinol coil stent grafting: preliminary report.

A method is described for the percutaneous catheter placement of expandable nitinol coil stents for the nonoperative restoration and maintenance of patency in internal flow pathways, especially the lumina of blood vessels and biliary ducts.