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Biomedical subjects

G Palmisano

Publications and source records attributed to G Palmisano.

15 recordsLinked to original sources
PubMed2001

Azomethine ylide cycloaddition/reductive heterocyclization approach to oxindole alkaloids: asymmetric synthesis of (-)-horsfiline.

The intermolecular [3 + 2] annulation of azomethine ylides with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed pi-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)-2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.

Alkaloids↗
PubMed2001

Molecular analysis of patients with relapsed or refractory intermediate-high grade non-Hodgkin's lymphoma with bone marrow infiltration undergoing peripheral blood progenitor cell transplantation.

BACKGROUND AND OBJECTIVES: IgH gene rearrangement studies with a polymerase chain reaction (PCR) technique can detect the persistence of clonal cells at molecular level during the remission phase. This persistence of clonal cells can be used to establish the relationship between minimal residual disease (MRD) and clinical outcome. We have developed a three-step single strand conformational polymorphism PCR strategy which is able to detect clonal B lymphoid cells at a frequency as low as 1 clonal cell in 10(6) normal cells. DESIGN AND METHODS: Twenty patients with intermediate or high-grade B non-Hodgkin's lymphoma (NHL) were evaluated. Patients were pre-treated with a median of two (range 1-4) conventional chemotherapy lines before high-dose cyclophosphamide (HDCY). All patients had their bone marrow (BM) involved by disease (median 10%; range 5-50%). Nineteen patients were offered high-dose therapy followed by peripheral blood progenitor cells (PBPC) autografting. RESULTS: MRD analysis was performed for each patient at the end of conventional chemotherapy and every three months after high dose therapy. All these patients achieved complete response (CR) after high dose therapy (HDT). Six patients relapsed after a median time of 24.5 months. All the studied apheresis samples were positive at the molecular analysis. All 6 patients still positive at the molecular analysis after PBPC autografting relapsed. The remaining 13 patients who were negative maintained CR. INTERPRETATION AND CONCLUSIONS: Whereas the detection of clonal cells in the apheresis samples did not predict an unfavorable outcome, the disappearance of the clonal rearranged band from the BM sample after HDT proved to be a favorable prognostic factor and was associated with long-lasting disease-free status

Adult↗
PubMed2000

[GdPCP2A(H(2)O)(2)](-): a paramagnetic contrast agent designed for improved applications in magnetic resonance imaging.

A novel ligand based on a pyridine-containing macrocycle bearing two acetic and one methylenephosphonic arms (PCP2A) has been synthesized. An efficient synthesis of PCP2A is based on the macrocyclization reaction between 2,6-bis(chloromethyl)pyridine and a 1,4, 7-triazaheptane derivative bearing a methylenephosphonate group on N-4. The Gd(III) complex of PCP2A displays characteristic properties which make it a very promising contrast agent for improved applications in magnetic resonance imaging. In fact it shows (i) a very high stability constant (log K(GdPCP2A) = 23.4) which should guarantee against the in vivo release of toxic free Gd(III) ions and free ligand molecules and (ii) a relaxivity that is about 2 times higher than the values reported for contrast agents currently used in the clinical practice. Its high relaxivity is the result of the presence of two water molecules in the inner coordination sphere and a significant contribution from water molecule(s) hydrogen bonded to the phosphonate group. Moreover, the inner sphere water molecules are involved in an exchange with the bulk water which is relatively fast. This property is important for the attainment of an even higher relaxivity once the molecular reorientation rate of the [GdPCP2A(H(2)O)(2)](-) moiety is lengthened by means of conjugation to a macromolecular substrate.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2000

Non-covalent conjugates between cationic polyamino acids and GdIII chelates: a route for seeking accumulation of MRI-contrast agents at tumor targeting sites.

Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of 1H- and 31P-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (1H and 17O) properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.

Chelating Agents↗
PubMed2000

Ternary Gd(III)L-HSA adducts: evidence for the replacement of inner-sphere water molecules by coordinating groups of the protein. Implications for the design of contrast agents for MRI.

Two novel gadolinium(III) chelates based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their relaxometric and luminescent properties thoroughly investigated. They contain two water molecules in the inner coordination sphere in fast exchange with the bulk solvent and bear either a p-bromobenzyl or a p-phosphonatomethylbenzanilido substituent for promoting further interaction with macromolecular substrates. Upon interaction with human serum albumin the expected relaxation enhancement is not observed owing to displacement of the two inner-sphere water molecules of the complexes by a donor atom (likely from a carboxylate group) on the protein and possibly the phosphate anion of the buffered solution, respectively. We modeled the observed behavior by measuring the decrease of the relaxation rate of the water protons upon addition of malonate anion to aqueous solutions of the complexes. Conversely, no change in the hydratation state of the Gd(III) center for both complexes has been observed when the substrate for the formation of the macromolecular adduct is represented by poly-beta-cyclodextrin.

Contrast Media↗
PubMed1999

An expeditious procedure for the isolation of ingenol from the seeds of euphorbia lathyris

A short and practical process for the isolation of ingenol (1a) from an agricultural commodity (the seeds of Euphorbia lathyris) is described. Macrocyclic diterpene esters are obtained as byproducts, and the esterification pattern of the Euphorbia factors L2 (3), L3 (4a), and L8 (4b) was established by 2D NMR measurements. Full spectroscopic data for these compounds are reported.

Journal Article↗
PubMed1996

Synthesis and evaluation of phorboid 20-homovanillates: discovery of a class of ligands binding to the vanilloid (capsaicin) receptor with different degrees of cooperativity.

A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [3H]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assay used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.

Animals↗
PubMed1993

Phase diagram of (R)- and (S)-4-hydroxy-2-pyrrolidone mixtures: a new case of a conglomerate-forming system.

The phase diagram of (R)- and (S)-4-hydroxy-2-pyrrolidone presents a conglomerate in the racemic mixture. The enthalpy of melting extrapolated by the Schröder-van Laar-Le Chatelier equation [change in enthalpy (delta H) = 28410 J/mol; melting temperature (TA) = 429.9 K; solidus temperature (Ts) = 395.4 K] and the value determined by differential scanning calorimetry (delta H = 28494 J/mol; TA = 429.6 K; Ts = 394.6 K) are in excellent agreement. The experimental entropy of the mixing of enantiomers is 5.69 J/mol.K. The conglomerate nature of the racemic mixture was confirmed by X-ray and IR spectroscopy. The presence of solvates was also observed.

Calorimetry, Differential Scanning↗
PubMed1992

Differential DNA binding properties of three human homeodomain proteins.

The products of three human homeobox containing (HOX) genes, 2C, 3C and 4B, were produced in insect cells using the Baculovirus expression system and purified to near homogeneity. In this system we observed that the DNA binding forms of the three proteins are not glycosylated. HOX 3C and 4B are phosphorylated in insect cells, while HOX 2C is not. The three HOX proteins bind to a DNA sequence known to be a target site for Antennapedia protein with a very similar affinity (Kd = 1-2 x 10(-9) M). We then measured their binding properties to four human sequences present in the HOX 3D, 4C, 1C and 4B promoters. Two of these sequences have been reported to be binding sites for HOX proteins. HOX 2C, 3C and 4B behaved quite differently, showing low affinity for promoters of genes located upstream from their own gene in the HOX clusters and a higher affinity for regulatory sequences of their own gene and downstream HOX genes.

Animals↗
PubMed1992

Autoxidation of tetrazepam in tablets: prediction of degradation impurities from the oxidative behavior in solution.

The major route of degradation of tetrazepam (1) is oxidation to 7-chloro-5-(3-keto-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2-one (3) via the stable 7-chloro-5-(3-hydroperoxy-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H -1, 4 benzodiazepin-2-one (2). Minor degradation products are 7-chloro-5-(1,2-epoxycyclohexan-1-yl)-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2-one (5) and 7-chloro-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2,5-dione (4), resulting from cleavage of the C-C bond between the cyclohexene ring and the benzodiazepine ring. After 48 h, AIBN (2,2'-azobis[2-methyl-propanenitrile]) in acetonitrile at 40 degrees C produced qualitatively the same impurities as those observed in the stability study of tablets of 1. Other stress tests (thermal stress at 80 degrees C, heavy metal oxidation, hydrogen peroxide, acid-catalyzed oxidation) caused qualitatively different profiles of degradation.

Anti-Anxiety Agents↗
PubMed1989

Diagnosis of ectopic pregnancy using transvaginal ultrasound scanning.

A new technique was developed for transvaginal ultrasound scanning in the routine evaluation of women with suspected early ectopic pregnancy. This approach enables us to detect early pregnancies that could not be visualized previously with routine abdominal ultrasound. Transvaginal scanning shows the location of the gestational sac very clearly, whether it is within or outside the uterus. Our introduction of this technique into the evaluation process has reduced patients' risk by minimizing delays in diagnosis and treatment and also has shortened hospital stays, thereby reducing costs.

Adolescent↗
PubMed1987

Plasma oxytocin increases in the human sexual response.

The purpose of this study was to determine whether plasma oxytocin (OT) levels change during human sexual responses and, if so, to demonstrate the temporal pattern of change. Plasma OT levels were measured by RIA before, during, and after private self-stimulation to orgasm in normal men (n = 9) and women (n = 13). Blood samples were collected continuously through indwelling venous catheters. The subjects pressed a signal to indicate the start and finish of orgasm/ejaculation. Objective assessment of sexual arousal and orgasm was obtained by measuring blood-pulse amplitude and electromyographic activity, recorded continuously throughout testing from an anal device containing a photoplethysmograph and electromyograph electrodes connected to a polygraph located in an adjacent room. These measures allowed collection of data from men and women of changes in blood flow and muscle activity in the lower pelvic/pubic area. Plasma OT levels increased during sexual arousal in both women and men and were significantly higher during orgasm/ejaculation than during prior baseline testing. We suggest that the temporal pattern of secretion could be related to smooth muscle contractions of the reproductive system during orgasm.

Adult↗
PubMedDate not supplied

Novel paramagnetic macromolecular complexes derived from the linkage of a macrocyclic Gd(III) complex to polyamino acids through a squaric acid moiety.

Macromolecular Gd(III) complexes may find useful application as contrast agents for magnetic resonance angiography (MRA). Herein two novel systems are reported, namely Gd(DO3ASQ)3-lys16 and Gd(DO3ASQ)30-orn114. Their syntheses are based on the ability of the squaric acid moiety to act as a linker between the DO3A (1,4,7, 10-tetraazacyclododecane-1,4,7-triacetic acid) chelate moiety and the polyamino acidic chain. Moreover, the squaric acid participates in the coordination cage of the Gd(III) ion. The investigation of 1H and 17O NMR relaxation processes of solvent water nuclei allowed a detailed characterization of the systems under study. Gd(DO3ASQ)30-orn114 displays a remarkable ability to enhance the water proton relaxation rate of its solutions, and it may be considered as potential contrast agent for MRA applications.

Contrast Media↗