A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology,toxicology, and some pharmaceutical aspects

Beneficial therapeutic effects of phenolic acids have been proven in various research projects including in vivo and in vitro studies. Gentisic acid (GA) is a phenolic acid that has been associated with useful effects on human health, such as antiinflammatory, antigenotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities. It is an important metabolite of aspirin and also widely distributed in plants as a secondary plant product such as Gentiana spp., Citrus spp., Vitis vinifera, Pterocarpus santalinus, Helianthus tuberosus, Hibiscus rosa‐sinensis, Olea europaea, and Sesamum indicum and in fruits such as avocados, batoko plum, kiwi fruits, apple, bitter melon, black berries, pears, and some mushrooms. This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.     

Vertebral fractures following stereotactic body radiotherapy for spine metastases

Stereotactic body radiotherapy has emerged as one of the preferred treatments for patients with spine metastases, with the potential for long‐term control from lesion irradiation. Post‐treatment vertebral compression fractures are a known complication of this therapy, contributing to worsening pain and reduced quality of life, sometimes requiring surgical intervention. This review explores the current knowledge of post‐radiotherapy fractures, in terms of the rates and associated predictive factors. A search of databases including Medline, Embase and the Cochrane Library was conducted using keywords such as ‘vertebral compression fracture’, ‘stereotactic body radiotherapy’ and ‘spine metastases’. The search was limited to published studies up to March 2019, reporting clinical outcomes including both the post‐treatment fracture rate and statistical identification of associated risk factors. Rates of post‐treatment fractures ranged from 4 to 39%. A variety of factors were found to increase the risk, including the appearance of lytic vertebral disease, degree of pre‐existing compression, spinal malalignment, increased dose per fraction and a Spinal Instability Neoplastic Score >6. This knowledge can enable clinicians to counsel patients when considering management options for spine metastases, maintaining the balance between local tumour control and the risk of subsequent fracture.     

Design,synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase

BackgroundAcetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease.MethodsColorimetric Ellman’s method was used for determination of IC₅₀ value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action.Result and discussionA new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC₅₀ = 11.51 μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC₅₀ = 1.95 μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10 μM.ConclusionIt is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. Graphical abstractOpen in a separate windowA new series of cinnamic-derived acids-tryptamine hybrid derivatives were designed, synthesized and evaluated as butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitors and neuroprotective agents. Compound 5b and 5q, as the more potent compounds, interacted with both the peripheral site and the choline binding site having mixed type inhibition. Results suggested that derivatives have a therapeutic potential for the treatment of AD.Electronic supplementary materialThe online version of this article (10.1007/s40199-020-00346-9) contains supplementary material, which is available to authorized users.     

Interreader and intermodality reliability of standard anteroposterior radiograph and magnetic resonance imaging in detection and classification of lumbosacral transitional vertebra

Background contextDifferent types of lumbosacral transitional vertebra (LSTV) are classified based on the relationship of the transverse process of the last lumbar vertebra to the sacrum. The Ferguson view (30° angled anteroposterior [AP] radiograph) is supposed to have a sufficient interreader reliability in classification of LSTV, but is not routinely available. Standard AP radiographs and magnetic resonance imaging (MRI) are often available, but their reliability in detection and classification of LSTV is unknown.PurposeThe purpose of this study was to evaluate the interreader reliability of detection and classification of LSTV with standard AP radiographs and report its accuracy by use of intermodality statistics compared with MRI as the gold standard.Study design/settingRetrospective case control study.Patient sampleA total of 155 subjects (93 cases: LSTV type 2 or higher; 62 controls).Outcome measuresInterreader reliability in detection and classification of LSTV using standard AP radiographs and coronal MRI as well as accuracy of radiographs compared with MRI.MethodsAfter institutional review board approval, coronal MRI scans and conventional AP radiographs of 155 subjects (93 LSTV type 2 or higher and 62 controls) were retrospectively reviewed by two independent, blinded readers and classified according to the Castellvi classification. Interreader reliability was assessed using kappa statistics for detection of an LSTV and identification of all subtypes (six variants; 1: no LSTV or type I, 2: LSTV type 2a, 3: LSTV type 2b, 4: LSTV type 3a, 5: LSTV type 3b, 6: LSTV type 4) for MRI scans and standard AP radiographs. Further, accuracy and positive and negative predictive values were calculated for standard AP radiographs to detect and classify LSTV using MRI as the gold standard.ResultsThe interreader reliability was at most moderate for the detection (k=0.53) and fair for classification (wk=0.39) of LSTV in standard AP radiograph. However, the interreader reliability was very good for detection (k=0.93) and classification (wk=0.83) of LSTV in MRI. The accuracy and positive and negative predictive values of standard AP radiograph were 76% to 84%, 72% to 86%, and 79% to 81% for the detection and 53% to 58%, 51% to 76%, and 49% to 55% for the classification of LSTV, respectively.ConclusionStandard AP radiographs are insufficient to detect or classify LSTV. Coronal MRI scans, however, are highly reliable for classification of LSTV.     

Biomechanical comparison of sagittal-parallel versus non-parallel pedicle screw placement

Background

While convergent placement of pedicle screws in the axial plane is known to be more advantageous biomechanically, surgeons intuitively aim toward a parallel placement of screws in the sagittal plane. It is however not clear whether parallel placement of screws in the sagittal plane is biomechanically superior to a non-parallel construct. The hypothesis of this study is that sagittal non-parallel pedicle screws do not have an inferior initial pull-out strength compared to parallel placed screws.

Methods

The established lumbar calf spine model was used for determination of pull-out strength in parallel and non-parallel intersegmental pedicle screw constructs. Each of six lumbar calf spines (L1-L6) was divided into three levels: L1/L2, L3/L4 and L5/L6. Each segment was randomly instrumented with pedicle screws (6/45 mm) with either the standard technique of sagittal parallel or non-parallel screw placement, respectively, under fluoroscopic control. CT was used to verify the intrapedicular positioning of all screws. The maximum pull-out forces and type of failure were registered and compared between the groups.

Results

The pull-out forces were 5,394 N (range 4,221 N to 8,342 N) for the sagittal non-parallel screws and 5,263 N (range 3,589 N to 7,554 N) for the sagittal-parallel screws (p?=?0.838). Interlevel comparisons also showed no statistically significant differences between the groups with no relevant difference in failure mode.

Conclusion

Non-parallel pedicle screws in the sagittal plane have at least equal initial fixation strength compared to parallel pedicle screws in the setting of the here performed cadaveric calf spine experiments.     

Severity of foraminal lumbar stenosis and the relation to clinical symptoms and response to periradicular infiltration—introduction of the “melting sign”

Background Context

Nerve root compression causing symptomatic radiculopathy can occur within the intervertebral foramen. Sagittal magnetic resonance imaging (MRI) sequences are reliable in detection of nerve root contact to intraforaminal disc material, but a clinically relevant classification of degree of contact is lacking.

Patient phenotypes associated with outcome following surgery for mild degenerative cervical myelopathy: a principal component regression analysis

Background Context

Predictors of outcome after surgery for degenerative cervical myelopathy (DCM) have been determined previously through hypothesis-driven multivariate statistical models that rely on a priori knowledge of potential confounders, exclude potentially important variables because of restrictions in model building, cannot include highly collinear variables in the same model, and ignore intrinsic correlations among variables.