Effect of counterion on the catalytic activity of NHC-gold(I) in A3 coupling reactions

Synthetic A3-coupling represents an efficient and environmentally convenient procedure for the production of propargylamines, relevant intermediates for the preparation of pharmacologically active substances. Gold(I) complexes of general formula NHC-Au-X have been synthesized, characterized, and tested in the A3-coupling reaction of benzaldehyde, piperidine and phenylacetylene on varying the anionic fragment X as halogenide (Cl, Br, I), acetate (OAc), hexafluorophosphate (PF6) or phenylacetylide (-C≡CPh), with 5-dichloro[N-methyl, N’(2-hydroxy-2-phenyl)ethyl imidazole-2-ylidene as NHC ligand. The kinetic profiles were interpreted with DFT (Density Functional Theory) studies on bond dissociation energies (BDE) of the counterion as well as on the relative stability of the neutral NHC-Au-X complexes with respect to their ionic forms [Au(NHC)2]+[AuX2]-

N-Heterocyclic Carbene Gold Complexes Active in Hydroamination and Hydration of Alkynes

Until the year 2000, gold compounds were considered catalytically inert. Subsequently, it was found that they are able to promote the nucleophilic attack on unsaturated substrates by forming an Au-pi-system. The main limitation in the use of these catalytic systems is the ease with which they decompose, which is avoided by stabilization with an ancillary ligand. N-heterocyclic carbenes (NHCs), having interesting sigma-donor capacities, are able to stabilize the gold complexes (Au (I/III) NHC), favoring the exploration of their catalytic activity. This review reports the state of the art (years 2007-2022) in the nucleophilic addition of amines (hydroamination) and water (hydration) to the terminal and internal alkynes catalyzed by N-heterocyclic carbene gold (I/III) complexes. These reactions are particularly interesting both because they are environmentally sustainable and because they lead to the production of important intermediates in the chemical and pharmaceutical industry. In fact, they have an atom economy of 100%, and lead to the formation of imines and enamines, as well as the formation of ketones and enols, all important scaffolds in the synthesis of bioactive molecules, drugs, heterocycles, polymers, and bulk and fine chemicals

Catalytic and biological activity of silver and gold complexes stabilized by nhc with hydroxy derivatives on nitrogen atoms

In this paper is reported the synthesis of N,N′ hydroxy derivative of NHC silver (3a–4a) and gold(I) (3b–4b) complexes of general formula [M(NHC)2 ]+ [MX2 ]−. All compounds were characterized by spectroscopic and analytic techniques. The complexes turned out to be effective in both catalytic and biological applications. They catalyzed the coupling of aldehyde, piperidine, and phenylacetylene in A3-reaction to produce propargylamines and showed antimicrobial activity. In fact, minimal inhibition concentration (MIC) tests with Gram-positive and Gram-negative bacteria demonstrated that the silver compounds are selective toward E. coli, whereas the gold analogues are active against S. aureus. Moreover, the N,N′ hydroxy derivative of NHC silver complexes 3a and 4a exhibited good anticancer activity on the HeLA cancer cells (3a-IC50 = 12.2 ± 0.1 µM, 4a-IC50 = 11.9 ± 1.2 µM), whereas gold complex 4b displayed good anticancer activity towards the MCF-7 cells (IC50 = 12.2 ± 1.2 µM)

Outcomes of decompression for lumbar spinal canal stenosis based upon preoperative radiographic severity

BACKGROUND: The relationship between severity of preoperative radiographic findings and surgical outcomes following decompression for lumbar degenerative spinal canal stenosis is unclear. Our aim in this paper was to gain insight into this relationship. We determined pre-operative radiographic severity on MRI scans using strict methodological controls and correlated such severity with post-operative outcomes using prospectively collected data. METHODS: Twenty-seven consecutive patients undergoing decompression for isolated degenerative spinal canal stenosis at L4-L5 were included. We measured cross-sectional area on MRI using the technique of Hamanishi. We categorized the severity of stenosis using Laurencin and Lipson's 'Stenosis Ratio'. We determined pre-operative status (prospectively) and post-operative outcomes using Weiner and Fraser's 'Neurogenic Claudication Outcome Score'. We determined patient satisfaction using standardized questionnaires. Each of these is a validated measure. Formal statistical evaluation was undertaken. RESULTS: No patients (0 of 14) with a greater than 50% reduction in cross-sectional area on pre-operative MRI had unsatisfactory outcomes. In contrast, outcomes for patients with less than or equal to 50% reduction in cross-sectional area had unsatifactory outcomes in 6 of 13 cases, with all but one negative outcome having a cross-sectional area reduction between 32% and 47%. CONCLUSION: The findings suggest that there appears to be a relationship between severity of stenosis and outcomes of decompressive surgery such that patients with a greater than 50% reduction in cross sectional area are more likely to have a successful outcome

National audit of post-operative management in spinal surgery

BACKGROUND: There is some evidence from a Cochrane review that rehabilitation following spinal surgery may be beneficial. METHODS: We conducted a survey of current post-operative practice amongst spinal surgeons in the United Kingdom in 2002 to determine whether such interventions are being included routinely in the post-operative management of spinal patients. The survey included all surgeons who were members of either the British Association of Spinal Surgeons (BASS) or the Society for Back Pain Research. Data on the characteristics of each surgeon and his or her current pattern of practice and post-operative care were collected via a reply-paid postal questionnaire. RESULTS: Usable responses were provided by 57% of the 89 surgeons included in the survey. Most surgeons (79%) had a routine post-operative management regime, but only 35% had a written set of instructions that they gave to their patients concerning this. Over half (55%) of surgeons do not send their patients for any physiotherapy after discharge, with an average of less than two sessions of treatment organised by those that refer for physiotherapy at all. Restrictions on lifting, sitting and driving showed considerable inconsistency both between surgeons and also within the recommendations given by individual surgeons. CONCLUSION: Demonstrable inconsistencies within and between spinal surgeons in their approaches to post-operative management can be interpreted as evidence of continuing and significant uncertainty across the sub-speciality as to what does constitute best care in these areas of practice. Conducting further large, rigorous, randomised controlled trials would be the best method for obtaining definitive answers to these questions

Prognosis of Surgical Treatment for Degenerative Lumbar Spinal Stenosis: A Prospective Cohort Study of Clinical Outcomes and Health-Related Quality of Life Across Gender and Age Groups

Degenerative lumbar spinal stenosis is a common condition and the most usual indication for spinal surgery in adult patients. The main objective of this study was to investigate clinical outcomes, health-related quality of life (HRQoL) and satisfaction among patients with a diagnosed lumbar spinal stenosis who were surgically treated, and whether these outcomes differed according to gender and age. Surgery was performed on 100 patients with clinical and radiological defined lumbar spinal stenosis. All patients completed questionnaires twice before surgery and at 6 weeks, 12 weeks, and 1 year postoperatively. Main outcomes were symptoms, physical function and patient satisfaction assessed by the Swiss Spinal Stenosis Questionnaire and HRQoL by the Short Form 36 health survey (SF36). There were large improvements in all clinical outcomes and in the physical subscales of the SF36. A marked reduction of average 32.3% was seen in symptoms already at 6 weeks follow-up. Physical function had improved with an average of 29.8% at 1-year follow-up. There was no statistical significant effect of age and gender on symptoms and physical function. Patients more than 65 years were significantly less satisfied at the 1-year follow-up as compared to the younger patients (p=0.012). This study showed that the majority of patients improved significantly in symptoms, physical function and physical HRQoL after surgery for degenerative lumbar spinal stenosis, regardless of age and gender. Age showed to be closely connected to satisfaction

Quantitative radiologic criteria for the diagnosis of lumbar spinal stenosis: a systematic literature review

Background: Beside symptoms and clinical signs radiological findings are crucial in the diagnosis of lumbar spinal stenosis (LSS). We investigate which quantitative radiological signs are described in the literature and which radilogical criteria are used to establish inclusion criteria in clincical studies evaluating different treatments in patients with lumbar spinal stenosis. Methods: A literature search was performed in Medline, Embase and the Cochrane library to identify papers reporting on radiological criteria to describe LSS and systematic reviews investigating the effects of different treatment modalities. Results: 25 studies reporting on radiological signs of LSS and four systematic reviews related to the evaluation of different treatments were found. Ten different parameters were identified to quantify lumbar spinal stenosis. Most often reported measures for central stenosis were antero-posterior diameter (< 10 mm) and cross-sectional area (< 70 mm2) of spinal canal. For lateral stenosis height and depth of the lateral recess, and for foraminal stenosis the foraminal diameter were typically used. Only four of 63 primary studies included in the systematic reviews reported on quantitative measures for defining inclusion criteria of patients in prognostic studies. Conclusions: There is a need for consensus on well-defined, unambiguous radiological criteria to define lumbar spinal stenosis in order to improve diagnostic accuracy and to formulate reliable inclusion criteria for clinical studies

Quality of life and functionality after total hip arthroplasty: a long-term follow-up study

<p>Abstract</p> <p>Background</p> <p>There is a lack of data on the long-term outcome of total hip arthroplasty procedures, as assessed by validated tools.</p> <p>Methods</p> <p>We conducted a follow-up study to evaluate the quality of life and functionality of 250 patients an average of 16 years (range: 11-23 years) after total hip arthroplasty using a validated assessment set including the SF-36 questionnaire, Harris Hip Score, WOMAC score, Functional Comorbidity Index, and a study specific questionnaire. Models of multiple stepwise linear and logistic regression analysis were constructed to evaluate the relationships between several explanatory variables and these functional outcomes.</p> <p>Results</p> <p>The SF-36 physical indexes of these patients compared negatively with the normative values but positively with the results obtained in untreated subjects with severe hip osteoarthritis. Similar results were detected for the Harris Hip Score and WOMAC score. There was a 96% rate of post-surgical satisfaction. Hip functionality and comorbidities were the most important determinants of physical measures on the SF-36.</p> <p>Conclusions</p> <p>Patients who had undergone total hip arthroplasty have impaired long-term self-reported physical quality of life and hip functionality but they still perform physically better than untreated patients with advanced hip osteoarthritis. However, the level of post-surgical satisfaction is high.</p

Structural and Functional Similarities between Osmotin from Nicotiana Tabacum Seeds and Human Adiponectin

Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico