The psychology of gastric bypass surgery.

BACKGROUND: This article discusses the importance of psychological evaluation of gastric bypass (GBP) surgery candidates and post-surgical psychological support services, using the Center for Weight Reduction Surgery at Montefiore Medical Center as a model. The study of psychological predictors of post-operative outcome is in its beginning stages, and the small body of literature on this topic is reviewed. METHODS: 115 GBP surgery candidates completed a clinical interview and a self-report measure, the MMPI-2. RESULTS AND CONCLUSIONS: A high prevalence of psychopathology and personality disturbance was found in this population. The impact that psychological disturbance may have on post-operative outcome is discussed. The authors also provide a qualitative analysis of the psychological themes commonly found among this population, as well as psychosocial interventions that have been found helpful.

Youth suicidal behavior: assessment and intervention.

In this article, the authors review the research on risk assessment of suicidal adolescents and describe the small body of randomized-clinical-treatment trials for this population. Research has yielded a fairly consistent set of direct and indirect risk factors for suicidal behavior in adolescents. The authors describe a variety of measures commonly used to assess these risk factors. Treatment studies targeting suicide are sparse for all ages. In the adult literature, evidence suggests clozapine, depot flupenthixol, lithium, and dialectical behavior therapy (DBT) are significantly more effective in decreasing suicidal behavior than placebo or Treatment as Usual. For adolescents, it is difficult to draw conclusions about treatment efficacy. In general, control conditions are just as effective at reducing suicidal behavior as experimental conditions. While some novel interventions for suicidal adolescents are described, there is a desperate need for more research to be conducted in order to advance this burgeoning field.

Purification and crystallization of rhizopuspepsin: the use of nickel chelation chromatography to select for catalytically active species.

A new method to obtain pure zymogen-derived peptidases is presented. The key strategy is to install a polyhistidine peptide tag on the N-terminus of the propeptide sequence of a zymogen. After expression, purification, and folding of the protein, autocatalytic posttranslational cleavage and filtration through a nickel affinity column gives pure, functional peptidase. This method takes advantage of the nickel affinity chromatography system that removes both zymogen peptide and nonfunctional folded peptidase without the need to use external enzymes to remove, often incompletely, the resulting fusion peptide. This technique was used to prepare the aspartic peptidase rhizopuspepsin. His-tagged rhizopuspepsinogen was expressed, and the desired protein was isolated as inclusion bodies and refolded. The proenzyme was purified by normal methods and then the relatively pure proenzyme was activated via intramolecular proteolysis at low pH. The propeptide and any inactive rhizopuspepsinogen were removed via affinity chromatography. This procedure yields a highly active rhizopuspepsin in 99% purity, which was demonstrated by PAGE, protein sequencing, and X-ray crystallography (1.5 A) of the isolated peptidase. A new fluorescent assay system is introduced for rhizopuspepsin, utilizing the substrate KPVSY(4-NO(3)-F)RL. The kinetics constants were K(m) = 3.4 microM +/- 0.31 and k(cat) = 55 +/- 1.0 s(-1).

[Polish students of the University of Halle - Wittenberg at the turn of XVII-XVIII centuries]. / Polscy studenci w Uniwersytecie Halle - Wittenberg na przelomie XVII-XVIII wieku.

The author had made a research study of the archives of the Martin Luther University in Halle Wittenburg (Germany) in search of students of Polish nationality or background. The edited version of the archives from years 1690-1730 and the original archives 1822-1931 were examined. The first part edited by Fritz Junke "Matrikel der Martin Luther Universitat Halle Wittenberg" in 1960 consists of the names of students and the names of their hometown. It does not contain the faculty of studies nor the nationality. The original archives of the years 1822-1931 contained the lists of students issued each semester as well as some personal files of a number of graduate students. They are original acts of students too. The following article refers to the archives of the year of 1690-1730. The study of the archives of the year 1822-1931 will follow.

Inactivation of cell surface receptors by pheophorbide a, a green pigment isolated from Psychotria acuminata.

The inhibition of cytokine and monoclonal antibody binding cell surfaces caused by an extract of Psychotria acuminata, a medicinal plant used in the traditional medicine of the people of Belize (Central Africa), was attributed to the presence of pheophorbide a and pyropheophorbide a. Since the binding of tumor necrosis factor-alpha, interleukin-8, complement factor 5a as well as epidermal growth factor to target cells was dramatically reduced, the inhibition was not receptor or cytokine specific. In addition, the respective binding of radiolabeled monoclonal antibodies CL203 and R15.7 to the cell surface antigens intracellular cell adhesion molecule-1 and lymphocyte function-associated antigen-1 beta-chain was decreased by pretreatment of cells with pheophorbide a as well. In all cases, the inhibition by pheophorbides was dependent on the simultaneous presence of light, indicating causative involvement of a photodynamic process. These observations are not unique to pheophorbides and can be extended to porphyrins as well as to other photodynamic agents. Cytotoxicity resulting from photodynamic therapy (PDT) has been documented by many studies. Our investigations suggest that the inactivation of cell surface receptors contributes not only to an antitumor effect of PDT but also to the systemic immunosuppression, a serious side effect of PDT.

Effect of the 7-amino substituent on the inhibitory potency of mechanism-based isocoumarin inhibitors for porcine pancreatic and human neutrophil elastases: a 1.85-A X-ray structure of the complex between porcine pancreatic elastase and 7-[(N-tosylphenylalanyl)amino]-4-chloro-3- methoxyisocoumarin.

A series of new acyl, urea, and carbonate derivatives of 7-amino-4-chloro-3-methoxyisocoumarin were synthesized and evaluated as irreversible inhibitors of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE). Inhibition of HNE is directly related to the hydrophobicity of the substituent on the 7-amino group. The N-Tos-Phe derivative (19) is the best HNE inhibitor with a second-order rate constant kobs/[I] = 200,000 M-1 s-1. The closest analogue in this series, the 3,3-diphenylpropionyl derivative 5, had a kobs/[I] = 130,000 M-1 s-1 with HNE. In contrast to the Tos-Phe derivative 19, phenylacetyl derivative 2 and carbonates 22 and 25 gave extremely stable enzyme-inhibitor complexes with deacylation half-lives longer than 48 h with both elastases. N-Phenylurea derivative 25 was the best inhibitor for PPE with a second-order rate constant kobs/[I] = 7300 M-1 s-1. The crystal structure of a complex of PPE with N-tosyl-Phe derivative 19 was determined at 1.85-A resolution and refined to a final R factor of 16.9%. The isocoumarin forms an acyl enzyme with Ser-195, while His-57 is near the inhibitor, but not covalently linked. The Tos-Phe makes a few hydrophobic contacts with the S' subsites of PPE, but appears to be interacting primarily with itself in the PPE structure. This region of HNE is more hydrophobic and modeling indicates that the inhibitor would probably make additional contacts with the enzyme.

Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity.

Taxol has shown good in vivo antitumor activity in a number of test systems. The formulation of taxol for antitumor testing has been difficult. Esterification at either C-2' or C-7 resulted in loss of in vitro tubulin assembly activity but not cytotoxicity. These observations suggested that esters at C-2' and/or C-7, which would tend to promote water solubility, might serve as useful prodrugs of taxol. The reaction of taxol with either succinic anhydride or glutaric anhydride in pyridine solution at room temperature gave the crystalline mono 2'-adducts 1b and 1f, respectively. Salts of these acids (1b, 1f, 1i) were formed by the addition of 1 equiv of the corresponding base, followed by evaporation and/or freeze-drying of the solvent(s). The salts had improved antitumor activity as compared to the free acids. The triethanolamine and N-methylglucamine salts showed greatly improved aqueous solubility and were more active than the sodium salts. The glutarate series was preferred because of the higher activity and the higher yields obtained. 2'-Glutaryltaxol (1f) was coupled with 3-(dimethylamino)-1-propylamine, using CDI, to form in excellent yield the amino amide 1o. The hydrochloride salt (1p) showed good solubility and was extremely potent and active. At 10 mg/kg, in the B16 screen, 1p gave a T/C of 352 with 5 out of 10 cures. In the MX-1 breast xenograft assay, this prodrug gave values of -100 at doses of 40 and 20 mg/kg, with all live animals being tumor free.

Pyrrolizidine alkaloids from Cynoglossum creticum. Synthesis of the pyrrolizidine alkaloids echinatine, rinderine, and analogues.

Reinvestigation of Cynoglossum creticum led to the isolation of the previously reported echinatine [1] and heliosupine [2] as well as rinderine [3], 7-angelylheliotridine [4] and a new alkaloid, cynoglossamine [5]. The structures have been determined by spectral means (ir, ms, 1H-13C HETCOR nmr), comparison with literature data and authentic samples, and/or syntheses. In addition, 1 and all three of its isomers 3, 6, and 7 and other semisynthetic analogues (8-13) were prepared and characterized.

Anonamine, C19H27NO7, neosenkirkine, C19H27NO6, and hydroxysenkirkine, C19H27NO7.CH3OH. Macrocyclic secopyrrolizidine alkaloids from Senecio anonymus Wood.

lambda(Mo K alpha) = 0.71069 A, T = 298 K. Anonamine (I) (12,21-dihydroxy-4-methyl-4,8-secosenecionan-8,11,16-trione): C19H27NO7, Mr = 381.2, monoclinic, C2, a = 24.247 (7), b = 8.766 (2), c = 9.072 (1) A, beta = 99.21 (2) degrees, U = 1903.3 (8) A3, Z = 4, Dm = 1.32 (1), D chi = 1.330 g cm-3, mu(Mo K alpha) = 1.09 cm-1, F(000) = 816. Neosenkirkine (II) (12-hydroxy-4-methyl-4,8-secosenecionan-8,11,16-trione): C19H27NO6, Mr = 365.2, monoclinic, C2, a = 24.45 (1), b = 8.781 (2), c = 9.029 (2) A, beta = 98.99 (3) degrees, U = 1915 (1) A3, Z = 4, Dm = 1.27 (1), D chi = 1.267 g cm-3, mu(Mo K alpha) = 1.01 cm-1, F(000) = 784. Hydroxysenkirkine (III) [12,18-dihydroxy-4-methyl-4,8-secosenecionan-8, 11,16-trione-methanol (1/1)]: C19H27NO7.CH3OH, Mr = 413.2, orthorhombic, P2(1)2(1)2(1), a = 9.052 (3), b = 13.150 (4), c = 17.404 (8) A, U = 2071 (1) A3, Z = 4, Dm = 1.33 (1), D chi = 1.325 g cm-3, mu(Mo K alpha) = 1.10 cm-1, F(000) = 888. Full-matrix least squares refinement converged at R values of 0.042, 0.043 and 0.051 for 3163, 2894 and 2896 reflections for (I), (II), (III), respectively. All three crystals exhibit hydrogen bonds, including intramolecular O11...HO12 and intermolecular O8...HO12. In addition, intermolecular hydrogen bonds appear in (I) between O21...HO21' and in (III) between O8...HOCH3. The observed N...C8 distances across the eight-membered otonecine rings were 2.200, 2.245 and 1.712 A in (I), (II) and (III) respectively.

Semisynthetic pyrrolizidine alkaloid N-oxide antitumor agents. Esters of heliotridine.

The C-9 and C-7 monoesters and C-7, C-9 diesters of heliotridine with (S)-(+) and (R)-(-)-2-hydroxy-2-phenylbutyric acid were prepared, converted into their N-oxides, and compared with the corresponding C-9 monoesters of retronecine in the in vivo P388 lymphocytic leukemia screen. Relative in vitro cytotoxicities of some of the free bases and their corresponding N-oxides were also measured against the A204 rhabdomyosarcoma cell line by using the soft agar colony forming assay. Stereochemistry at C-7 of the necine and at C-2' of the necine acid appears to have a significant effect on the antitumor activity in this system. In the heliotridine series, the configuration of the necic acid has a pronounced effect on the site selectivity (C-7 vs C-9) in esterification with carbodiimidazole. An explanation for this site selectivity is offered.

Macrocyclic pyrrolizidine alkaloids from Senecio anonymus. Separation of a complex alkaloid extract using droplet counter-current chromatography.

Ten 12-membered macrocyclic pyrrolizidine alkaloids, all of them esters of the necines, retronecine or otonecine, have been isolated from Senecio anonymus. The separation, carried out by droplet counter-current chromatography, afforded senecionine [1], integerrimine [2], retrorsine [3], senkirkine [5], neosenkirkine [6], otosenine [10], hydroxysenkirkine [7], and a new alkaloid given the trivial name anonamine [9]. Traces of usaramine [4] and another new alkaloid, hydroxyneosenkirkine [8], were detected by 1H nmr. In addition, the previously unreported 3a beta-hydroxy-4-ethoxy-2,6-perhydroindoledione [11] was isolated. X-ray structures were obtained for neosenkirkine [6], hydroxysenkirkine [7], anonamine [9], and [11]. 1H-13C heteronuclear shift correlated nmr (HETCOR) provided unambiguous chemical shift assignments for 13C-nmr data. Antitumor activity was assayed using the A204-rhabdomyosarcoma cell line in soft agarose.

Synthesis of pyrrolizidine alkaloids indicine, intermedine, lycopsamine, and analogues and their N-oxides. Potential antitumor agents.

(-)- and (+)-trachelanthic and (-)- and (+)-viridifloric acids were synthesized and their isopropylidene derivatives were regiospecifically coupled, at C-9, with (-)-retronecine obtained by hydrolysis of monocrotaline, isolated from Crotalaria spectabilis. Hydrolysis, followed by oxidation, led to the N-oxides of indicine, intermedine, lycopsamine, and the new nonnatural product, respectively. Each of these analogues was screened in the P388 lymphocytic leukemia system at the same time as indicine N-oxide, and the results were compared. Other related analogues were prepared and similarly screened and the results compared with those from indicine N-oxide.