Biomimetic synthesis of galantamine via laccase/TEMPO mediated oxidative coupling

Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine. High yield and conversion of substrate were obtained in the presence of the redox mediator 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). This laccase procedure, with an overall yield of 34%, represents a scalable and environmentally friendly alternative to previously reported syntheses of galantamine based on the use of potassium ferricyanide as an unspecific radical coupling reagent.

Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine.     

The rational of forehead lifting in patients with chronic facial paralysis

Background

The incidence of permanent facial sequels in patients with Bell’s palsy is about 30 % and results in impaired mimic expression of both midface and forehead in varying degrees. Even at rest, most patients experience an imbalance of their facial features. In this article, static correction of brow imbalance was evaluated in patients with sequels after unilateral facial palsy.

Methods

Thirty-one patients with sequels of Bell’s palsy underwent surgery with endoscopic forehead lift. Brow position was geometrically assessed pre- and postoperatively. The validated self-assessment instrument for quality of life [Short Form 36(SF-36)] was completed prior to and after surgery. The follow-up period was 12 months.

Results

A notable improvement in the position of the brows was demonstrated over time with lasting results. All patients experienced an improvement in facial symmetry and balance at rest. However, no significant difference could be shown using SF-36 pre- and postoperatively.

Conclusion

Endoscopic forehead lift combined or as an isolated procedure is a valuable instrument to correct sequels of Bell’s palsy. Level of Evidence: Level IV, therapeutic study.     

Reactive Tonsillar Enlargement Showing Strong 18F-Fdg Uptake During the Follow-Up of Follicular Lymphoma

The ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a standard procedure for the diagnosis, staging, and restaging in lymphoma patients. However, a relative high rate of false-positive results has been reported. We report a case of a 40-year-old man with a previous history of a nodal follicular lymphoma, stage IVA, treated with R-CHOP, which showed strong ¹⁸F-FDG uptake in the Waldeyer’s tonsillar ring during his follow-up, being considered highly suspicious of relapsed lymphoma. A surgical removal of the palatine tonsils and adenoids was performed, which showed reactive follicular hyperplasia. Furthermore, bone marrow biopsy revealed absence of neoplasia. The patient is still in follow-up with no signs of recurrent lymphoma. This case illustrates that, despite the high sensitivity for the detection of recurrent lymphoma, ¹⁸F-FDG uptake should be interpreted with great caution and confirmatory studies should be performed before any therapy.     

Locally-applied Collagenase and Regeneration of Transsected and Repaired Rat Sciatic Nerves

The possible effects of collagenase on peripheral nerve regeneration were evaluated after epineurial repair of rat sciatic nerves. In the control group the repair site was covered by fibrin adhesive and infused with isotonic saline and in the experimental group collagenase was infused into the fibrin adhesive. In the short term study the regeneration distance was measured by a pinch test four, six, or eight days postoperatively. In the long term study the evaluation of nerve regeneration and recovery of motor function was made by testing the tetanic contraction force of the anterior tibial muscle three months postoperatively. There were no significant differences between the two groups in either the short or long term. We conclude that locally-applied collagenase had no effect on peripheral nerve regeneration.     

Genetic basis of non-syndromic anomalies of human tooth number

Teeth organogenesis develops through a well-ordered series of inductive events involving genes and BMP, FGF, SHH and WNT represent the main signalling pathways that regulate epithelial-mesenchymal interactions. Moreover, progress in genetics and molecular biology indicates that more than 300 genes are involved in different phases of teeth development. Mutations in genes involved in odontogenesis are responsible for many dental anomalies, including a number of dental anomalies that can be associated with other systemic skeletal or organic manifestations (syndromic dental anomalies) or not (non-syndromic dental anomalies). The knowledge of the genetic development mechanisms of the latter is of major interest. Understanding the mechanisms of pathogenesis of non-syndromic teeth anomalies would also clarify the role of teeth in craniofacial development, and this would represent an important contribution to the diagnosis, treatment and prognosis of congenital malformations, and the eventual association to other severe diseases. Future research in this area is likely to lead to the development of tests for doctors to formulate an early diagnosis of these anomalies.     

Pentoxifylline and propentofylline prevent proliferation and activation of the mammalian target of rapamycin and mitogen activated protein kinase in cultured spinal astrocytes

Astrocyte activation is an important feature in many disorders of the central nervous system, including chronic pain conditions. Activation of astrocytes is characterized by a change in morphology, including hypertrophy and increased size of processes, proliferation, and an increased production of proinflammatory mediators. The xanthine derivatives pentoxifylline and propentofylline are commonly used experimentally as glial inhibitors. These compounds are generally believed to attenuate glial activity by raising cyclic AMP (cAMP) levels and inhibiting glial tumor necrosis factor (TNF) production. In the present study, we show that these substances inhibit TNF and serum‐induced astrocyte proliferation and signaling through the mammalian target of rapamycin (mTOR) pathway, demonstrated by decreased levels of phosphorylated S6 kinase (S6K), commonly used as a marker of mTOR complex (mTORC) activation. Furthermore, we show that pentoxifylline and propentofylline also inhibit JNK and p38, but not ERK, activation induced by TNF. In addition, the JNK antagonist SP600125, but not the p38 inhibitor SB203580, prevents TNF‐induced activation of S6 kinase, suggesting that pentoxifylline and propentofylline may regulate mTORC activity in spinal astrocytes partially through inhibition of the JNK pathway. Our results suggest that pentoxifylline and propentofylline inhibit astrocyte activity in a broad fashion by attenuating flux through specific pathways. © 2012 Wiley Periodicals, Inc.     

Subthalamic deep brain stimulation affects heading perception in Parkinson’s disease

Journal of Neurology - Parkinson’s disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates...     

Age estimation in the Mediterranean bottlenose dolphin Tursiops truncatus (Montagu 1821) by bone density of the thoracic limb

The determination of age is an important step in defining the life history traits of individuals and populations. Age determination of odontocetes is mainly based on counting annual growth layer groups in the teeth. However, this useful method is always invasive, requiring the cutting of at least one tooth, and sometimes the results are difficult to interpret. Based on the concept that bone matrix is constantly deposited throughout life, we analysed the bone mineral density of the arm and forearm of a series of bottlenose dolphins (Tursiops truncatus, Montagu 1821) stranded along the Italian coast of the Adriatic Sea or maintained in confined waters. The bone mineral density values we obtained were evaluated as possible age predictors of the Mediterranean population of this species, considering age as determined by counting growth layer groups in sections of the teeth and the total body length of the animal as references. Comparisons between left and right flipper showed no difference. Our results show that bone mineral density values of the thoracic limb are indeed reliable age predictors in Tursiops truncatus. Further investigations in additional odontocete species are necessary to provide strong evidence of the reliability of bone mineral density as an indicator of growth and chronological wear and tear in toothed-whales.