Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

Single-level anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cage and allograft bone

BACKGROUND: In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages in combination with allograft bone are used to achieve fusion. The goal of the current study was to assess the reliability and efficacy of anterior cervical discectomy and interbody fusion (ACDF) using a PEEK anatomical cervical cage in the treatment of patients affected by single-level cervical degenerative disease. METHODS AND MATERIALS: Twenty-five patients affected by single-level cervical degenerative pathology between C4 and C7 were enrolled in this study. The clinical findings were assessed using the Neck Disability Index and the Visual Analog Scale. Surgical outcomes were rated according to Odom's criteria at last follow-up. Fusion was graded as poor, average, good or excellent by assessing the radiographs. Cervical spine alignment was evaluated by sagittal segmental alignment and sagittal alignment of the whole cervical spine preoperatively, 6 months postoperatively and at the last follow-up. RESULTS: Twenty-five patients underwent ACDF using a PEEK anatomical cervical cage. All patients had a minimum 2 years of follow-up. The operative levels were C4-C5 in 5 patients, C5-C6 in 12 patients and C6-C7 in 8 patients. Preoperatively, average NDI was 34, 13 at 6 months, and 10 at latest follow-up. The mean preoperative VAS was 7; the mean postoperative VAS at latest follow-up was 3. Good or excellent fusion was achieved in all patients within 10 months (mean 5 months). Preoperatively, average sagittal segmental alignment (SSA) was 0.2\ub0 and average sagittal alignment of the cervical spine (SACS) 15.8\ub0. Six months after surgery, average SSA was 1.8\ub0 and average SACS 20.9\ub0, and at last follow-up, average SSA was 1.6\ub0 and average SACS 18.5\ub0. CONCLUSION: Anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cages can be considered a safe and effective technique to cure cervical disc herniation with intractable pain or neural deficit in cases where conservative treatment failed

Congenital hip dysplasia treated by total hip arthroplasty using cementless tapered stem in patients younger than 50 years old: results after 12-years follow-up

Background Congenital hip dysplasia may lead to severe acetabular and femoral abnormalities that can make total hip arthroplasty a challenging procedure. We assessed a series of patients affected by developmental hip dysplasia treated with total hip arthroplasty using cementless tapered stem and here we report the outcomes at long-term follow-up. Materials and methods Twenty-eight patients (24 women and 4 men) aged between 44 and 50 years (mean 47 years) were observed. Clinical evaluation was rated with the Harris Hip Score. Radiographic evaluation consisted in standard anteroposterior and axial view radiographs of the hip. According to Crowe’s classification, 16 hips presented dysplasia grade 1, 14 grade 2, and 4 grade 3. All patients were treated with total hip arthroplasty using a cementless tapered stem (Wagner Cone Prosthesis). Six patients were operated bilaterally, with a totally of 34 hips operated. After surgery, the patients were clinically and radiographically checked at 3, 6, and 12 months and yearly thereafter until an average follow-up of 12 years (range 10–14 years). Results Average Harris Hip Score was 56 ± 9 (range 45–69) preoperatively, 90 ± 9 (range 81–100) 12 months after surgery, and 91 ± 8 (range 83–100) at last follow-up. Radiographic evaluation demonstrated excellent osteointegration of the implants. Signs of bone resorption were present in 6 hips, nevertheless no evidence of loosening was observed and none of the implants has been revised. Conclusions Even in dysplasic femur, the tapered stem allowed adequate stability and orientation of the implant. We consider tapered stem a suitable option for total hip arthroplasty in developmental hip dysplasia, also in case of young patients, thanks to the favourable long-term results

A Mechanistic Insight into the Cu(II)-Catalyzed C–N and C–O Coupling Reaction of Arylglyoxylic Acids with Isatins; A DFT Investigation

We carried out a DFT computational investigation on the mechanism of the copper(II) catalyzed C–N, C–O cross coupling reaction involving isatin and phenylglyoxylic acid recently reported by Gogoi. The mechanistic hypothesis proposed by this author is overall confirmed. Our computations demonstrated that the initial decarboxylation is an exergonic reaction (–15.3 kcal mol–1). This process, which can occur rather easily under the used experimental conditions (95 °C for 24 hours), triggers the catalytic cycle with the formation of the initial active organometallic complex (I1). A copper acetate ligand deprotonates the isatin nitrogen. This enhances its nucleophilic character and makes possible the attack of nitrogen on the Cu atom. A reversible transformation connects the initial encounter complex between isatin and the active intermediate I1 and the intermediate where the metal atom inserts into the amide bond. The decarbonylation step represents the rate-determining step of the entire process (activation free energy = 23.3 kcal mol–1). Copper does not change its oxidation state (II) in the course of the catalytic reaction. The mechanism never involves directly the isatin benzene ring: this is consistent with the fact that only slight changes in the reaction yield are observed when substituents are inserted at different positions of the aromatic ring

Cuboid osteotomy associated with plantar medial release in severe untreated clubfoot

The idiopathic congenital clubfoot or equinovarus consists of a deformity of the foot in equinus, varus and supination, that appears at birth. If it is detected until 3 years of age, the deformity can be successfully treated conservatively; if it is detected until 6 years, it can be treated by plantar medial release. If the deformity is observed later, it is usually more stiff and non reducible: the lateral column of the foot (calcaneous and cuboid) grows faster than the medial column (talus, navicular and cuneiform). The aim of this video is to show the treatment of neglected congenital equinovarus by plantar medial release associated with cuboid osteotomy in a 6 Y/O patient. In neglected congenital equinovarus in patients from 6 years of age, the posterior and medial tendons and capsules are retracted; the correction consists in lengthening of medial and posterior tendons, associated with the talonavicular capsulotomy. On the lateral aspect, by an oscillating saw, the osteotomy of the cuboid bone is performed. A little wedge with the base on the supero-lateral aspect is removed. The wedge osteotomy of the cuboid bone will lead to the shortening of the lateral column; this process permits the complete reduction of the varus and the adduction deformity of the foot. In neglected congenital equinovarus in patients from 6 years of age, the posterior and medial tendons and capsules are retracted, and the lateral column is longer than the medial; the plantar medial release associated with cuboid osteotomy is a good technique to correct the deformity without stiffness of the joints. The young patient can regain the neutral position of the foot; so he can wear shoes, stand up and walk correctly

Medial Plantar Release in Nonreducible Congenital Equinovarus Foot

The idiopathic congenital clubfoot, also known as equinovarus deformity or talipes equinovarus, is considered since now a deformity difficult to treat. Treatment of clubfoot starts at birth: depending on the stiffness of the deformity, gradual manipulations are performed, then plastercast and frames are applied. Only in some cases the surgical treatment is required. Some feet are extremely rigid and very little changes are visible after manipulation; these are usually smaller, stubby feet. If a clubfoot is not treated, at the age of walk, the foot stances only on its lateral aspect. The effect of weightbearing on a clubfoot worsen the varus and supination deformities, making the walk unstable and painful. The aim of this video is to show step by step the surgical treatment of a non reducible idiopathic equinovarus deformity between 2 and 6 years of age, operated by medial plantar release. The surgical procedure consisted in lengthening of the medial tendons of the foot; capsulotomy of the talo-navicular joint, repositioning the navicular bone on the talar head, and capsulotomy of the naviculo-cuneiform joints in order to reduce the varus deformity; and finally Achilles tendon lenghtening. Medial plantar release is still an actual surgical technique, but its indication is reserved for those feet in which the conservative treatment failed, or when the child is observed after walking age with a non reducible deformity, in which, otherwise, conservative treatment should be continued for a long period

Current classification systems for adult degenerative scoliosis

At present, a big effort of the scientific community has been directed toward a more proper and standardized approach to the patients affected by degenerative scoliosis, and recent attention has turned toward the development of classification schemes. A literature analysis highlighted several classification schemes developed for degenerative scoliosis patients: the Simmons classification system, the Aebi system, the Faldini working classification system, the Schwab system, and the Scoliosis Research Society system. Aim of the current manuscript is to scrutinize the available literature in order to provide a comprehensive overview of these current classification schemes for adult scoliosis, by describing and commenting clinical development, limits and potential of their application together with their implications for surgical plannin