Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

The enantioselectivity of β-cyclodextrin (β-CD) towards L- and D-N-acetyltryptophan (NAcTrp) has been studied in aqueous solution and the crystalline state. NMR studies in solution show that β-CD forms complexes of very similar but not identical geometry with both L- and D-NAcTrp and exhibits stronger binding with L-NAcTrp. In the crystalline state, only β-CD-L-NAcTrp crystallizes readily from aqueous solutions as a dimeric complex (two hosts enclosing two guest molecules). In contrast, crystals of the complex β-CD-D-NAcTrp were never obtained, although numerous conditions were tried. In aqueous solution, the orientation of the guest in both complexes is different than in the β-CD-L-NAcTrp complex in the crystal. Overall, the study shows that subtle differences observed between the β-CD-L,D-NAcTrp complexes in aqueous solution are magnified at the onset of crystallization, as a consequence of accumulation of many soft host-guest interactions and of the imposed crystallographic order, thus resulting in very dissimilar propensity of each enantiomer to produce crystals with β-CD

Oncology and complications.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy

CGRP and migraine from a cardiovascular point of view: what do we expect from blocking CGRP?

Calcitonin gene-related peptide (CGRP) is a neuropeptide with a pivotal role in the pathophysiology of migraine. Blockade of CGRP is a new therapeutic target for patients with migraine. CGRP and its receptors are distributed not only in the central and peripheral nervous system but also in the cardiovascular system, both in blood vessels and in the heart. We reviewed the current evidence on the role of CGRP in the cardiovascular system in order to understand the possible short- and long-term effect of CGRP blockade with monoclonal antibodies in migraineurs. In physiological conditions, CGRP has important vasodilating effects and is thought to protect organs from ischemia. Despite the aforementioned cardiovascular implication, preventive treatment with CGRP antibodies has shown no relevant cardiovascular side effects. Results from long-term trials and from real life are now needed

Mucinous cystic neoplasms of the mesentery: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site.</p> <p>Case presentation</p> <p>A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma.</p> <p>Methods and results</p> <p>We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors.</p> <p>Conclusion</p> <p>Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed.</p

Release of the Prays oleae pheromone as a consequence of supramolecular structure: study of the \u3b2-cyclodextrin-(Z)-tetradec-7-en-1-al complex by X-ray crystallography and NMR spectroscopy in the solid state and in solution

The structure of the \u3b2-cyclodextrin-(Z)-tetradec-7-en-1-al complex in aqueous solution and in the solid state, as well as the release profile of the (Z)-tetradec-7-en-1-al (sex pheromone of the olive pest Prays oleae) from the solid complex was investigated, in an effort to correlate the supramolecular structure with the macroscopic property of spontaneous liberation of the pheromone. It was observed that in solution a 2 36 1 host 36 guest complex prevails, having the guest in a curled configuration. In the crystal structure of the complex, two \u3b2-CD molecules forming head-to-head dimers and packed in channels enclose one guest molecule whose methyl terminal aliphatic chain curls at the cis-double bond and runs along the intradimer interface. In the space between host molecules there is also entrapped an additional pheromone molecule, also visible in the IR spectra, which is heavily disordered. The guest inside the cavity is disordered over two sites and exhibits mobility, especially at the methyl and carbonyl end-groups, which is also confirmed by solid state NMR experiments. Thus, there are two types of guest molecules in the crystalline complex, one inside the \u3b2-CD cavity and another trapped and held loosely outside the cavity. The release behavior, studied by NMR, shows that the \u201coutside\u201d pheromone is liberated from the solid initially at a fast rate, which reaches very low levels when almost half of the guest molecules have been released. The other half, molecularly encapsulated in the \u3b2-CD cavity, is well stabilized.NRC publication: Ye

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

β-Cyclodextrin (β-CD) dimers have been prepared using the bioorthogonal Staudinger ligation for the first time. In addition to a known linker, methyl 2-(diphenylphosphanyl)terephthalate, a doubly active linker was specifically developed that enabled connection of two β-CD units in a single step and in aqueous/organic media, under mild conditions and with good yields. A three-carbon spacer between the β-CD torus and the azido group was required for facile dimer formation. The products, as studied by NMR spectroscopy, were found to adopt closed conformations by intramolecular self-inclusion. On the other hand, association via intermolecular binding was also observed in aqueous solution, confirmed by DOSY NMR experiments. Despite self-inclusion, the β-CD cavities were capable of guest encapsulation, as shown by titration experiments: the binding constant with 1-adamantylamine was similar to that of natural β-CD. Theoretical calculations for isolated molecules (PM3 level of theory) and in the presence of solvent [water, PM3(COSMO)] as well as DFT calculations suggested that the compounds prefer to adopt conformations which bring the phenyl groups either inside the β-CD cavity (inclusion) or over its narrow side (vicinal). Thus, Staudinger ligation could be the method of choice for linking CDs exhibiting (i) ease of preparation in aqueous media, in short steps, under mild conditions and in good yields, (ii) satisfactory aqueous solubility and independent binding capacity of the cavities