Alternative technique of C1-2-3 stabilization-sectioning of muscles attached to C2 spinous process and C2-3 fixation.

AIM: An alternative technique of C1-2-3 fixation is described that blocks the critical anteroposterior odontoid process movements and retains rotatory movement at the atlantoaxial joint. The technique involves sharp section of the muscles attached to the C2 spinous process and C2-3 transarticular interfacetal screw fixation. MATERIALS AND METHODS: We successfully used this technique of fixation in 14 cases wherein in similar case situation; we earlier advocated inclusion of C1 in the fixation construct. Eleven patients had multisegmental spinal degeneration, 1 patient had Hirayama disease, and 2 patients had ossified posterior longitudinal ligament. RESULTS AND TECHNICAL ADVANTAGES: The procedure avoids manipulating C1 vertebra and excludes it from the fixation process, disables movement of C2 vertebra but retains rotation movements of the atlantoaxial joint that are executed by the muscles attached to the transverse process of atlas. The net effect is that the anteroposterior odontoid process movements that threaten the cervicomedullary neural structures are blocked and the critical rotatory atlantoaxial movements are retained. CONCLUSIONS: The discussed technique can be useful for cases undergoing multisegmental fixation that includes atlantoaxial joint.

Atlantoaxial Fixation for Odontoid Fracture: Analysis of 124 Surgically Treated Cases.

OBJECTIVE: The authors analyze 124 cases with fracture of odontoid process. All patients were surgically treated by posterior atlantoaxial fixation. METHODS: There were 96 male and 28 female patients. The ages of the patients ranged from 12 to 80 years. Apart from Anderson and D'Alonzo type I (6 cases), type II (93 cases) and type III (25 cases), three sub-types of odontoid fractures were included in the classification. In type A (118 cases), there was vertical compression fracture that resulted in malalignment of the fractured odontoid process segments. Type B (49 cases) resulted when the fracture resulted in malalignment of the facets of atlas and axis. Type C (25 cases) included cases in which the fracture line involved the facet of axis. Fractures were divided into acute type when the injury was less than 3 months old (50 cases), delayed type when the injury was between 3 months to one year (34 cases) and chronic type when the injury was more than 1 year in duration (40 cases). All patients were treated with posterior atlantoaxial fixation with the techniques described in 1994 and 2004. Follow-up period ranged from 6 to 156 months (average 72 months). RESULTS: All patients improved in symptoms after surgery. There were no significant postoperative complications. CONCLUSIONS: Posterior atlantoaxial stabilization forms a safe surgical strategy for all kinds of odontoid fractures. Additional characteristics of odontoid fractures further subclassified them and assisted in surgical decision-making and in formulating the surgical strategy.

C1-2 and C2-3 Instability in the Presence of Hypoplastic Posterior Elements of C2 Vertebra: Report of 2 Cases.

BACKGROUND: We present 2 cases involving a previously unreported clinical situation in which basilar invagination, atlantoaxial instability, and C2-3 instability were associated with a bifid posterior arch of the axis bone. CASE DESCRIPTIONS: Two young males presented with limb weakness, spasticity, and paresthesias. Both patients had altered voice quality, with reduced and thin volume, and difficulty sleeping supine. Radiologic imaging showed an absence of the posterior elements of the C2 vertebrae. The C3 spinous process mimicked the C2 spinous process in shape and size. C1-2 and C2-3 posterior fixations were performed. CONCLUSIONS: C1-2 and C2-3 fixation resulted in firm fixation of the region and a remarkable clinical recovery. The most significant features were an immediate postoperative improvement in voice quality and the ability to sleep comfortably in the supine position.

Dyeing of Polyester and Nylon with Semi-synthetic Azo Dye by Chemical Modification of Natural Source Areca Nut.

Various azo compounds (Modified dyes) have been synthesised by chemical modification of areca nut extract (epicatechin), a plant-based Polyphenolic compound to get semi-synthetic dyes. Three different primary amines namely p- nitro aniline, p-anisidine and aniline, were diazotized to form their corresponding diazonium salts which were further coupled with an areca nut extract. Preliminary characterization of the areca nut extract and the resultant azo compounds (Modified dyes) was carried out in terms of melting point, solubility tests, thin layer chromatography, UV-Visible and FTIR spectroscopy. These modified dyes were further applied on polyester and nylon fabrics and % dye exhaustion was evaluated. Dyed fabrics were further tested for their fastness properties such as wash fastness, rubbing fastness, light fastness and sublimation fastness. The results of the fastness tests indicate that, all the three modified dyes have good dyeability for polyester and nylon fabrics. The dyed fabrics were also tested for ultraviolet protection factor which showed very good ultraviolet protection.

Neuroprotective Role of Atractylenolide-I in an In Vitro and In Vivo Model of Parkinson's Disease.

Parkinson's disease (PD) is an age-related neurological disorder characterized by a loss of dopaminergic neurons within the midbrain. Neuroinflammation has been nominated as one of the key pathogenic features of PD. Recently, the inadequate pharmacotherapy and adverse effects of conventional drugs have spurred the development of unconventional medications in the treatment of PD. The purpose of this study is to investigate the anti-neuroinflammatory mechanisms of Atractylenolide-I (ATR-I) in in vivo and in vitro models of PD. Nitrite assay was measured via Griess reaction in lipopolysaccharide (LPS) stimulated BV-2 cells. mRNA and protein levels were determined by a reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analysis, respectively. Further, flow cytometry, immunocytochemistry, and immunohistochemistry were employed in BV-2 cells and MPTP-intoxicated C57BL6/J mice. Pre-treatment with ATR-I attenuated the inflammatory response in BV-2 cells by abating the nuclear translocation of nuclear factor-κB (NF-κB) and by inducing heme oxygenase-1 (HO-1). The intraperitoneal administration of ATR-I reversed MPTP-induced behavioral deficits, decreased microglial activation, and conferred protection to dopaminergic neurons in the mouse model of PD. Our experimental reports establish the involvement of multiple benevolent molecular events by ATR-I in MPTP-induced toxicity, which may aid in the development of ATR-I as a new therapeutic agent for the treatment of PD.

Atractylenolide-I Protects Human SH-SY5Y Cells from 1-Methyl-4-Phenylpyridinium-Induced Apoptotic Cell Death.

Oxidative stress and apoptosis are the major mechanisms that induce dopaminergic cell death. Our study investigates the protective effects of atractylenolide-I (ATR-I) on 1-methyl-4-phenylpyridinium (MPP⁺)-induced cytotoxicity in human dopaminergic SH-SY5Y cells, as well as its underlying mechanism. Our experimental data indicates that ATR-I significantly inhibits the loss of cell viability induced by MPP⁺ in SH-SY5Y cells. To further unravel the mechanism, we examined the effect of ATR-I on MPP⁺-induced apoptotic cell death characterized by an increase in the Bax/Bcl-2 mRNA ratio, the release of cytochrome-c, and the activation of caspase-3 leading to elevated levels of cleaved poly(ADP-ribose) polymerase (PARP) resulting in SH-SY5Y cell death. Our results demonstrated that ATR-I decreases the level of pro-apoptotic proteins induced by MPP⁺ and also restored Bax/Bcl-2 mRNA levels, which are critical for inducing apoptosis. In addition, ATR-I demonstrated a significant increase in the protein expression of heme-oxygenase in MPP⁺-treated SH-SY5Y cells. These results suggest that the pharmacological effect of ATR-I may be, at least in part, caused by the reduction in pro-apoptotic signals and also by induction of anti-oxidant protein.

Recent Update on the Role of Chinese Material Medica and Formulations in Diabetic Retinopathy.

Diabetes mellitus is one of the most frequent endocrine disorders, affecting populations worldwide. Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes in patients aged 20 and over. Major complications of DR include intraocular neovascularization, inter-retinal edema, hemorrhage, exudates and microaneurysms. Therefore, timely medical attention and prevention are required. At present, laser-assisted therapy and other operational procedures are the most common treatment for DR. However, these treatments can cause retinal damage and scarring. Also, use of the majority of traditional medicines is not supported by clinical evidence. However, due to accumulating scientific evidence, traditional natural medications may assist in delaying or preventing the progression of DR. This review focuses on evidence for the role of traditional natural medicines and their mechanisms of action and pharmacological test results in relation to the progression of DR.

Only spinal fixation as treatment of prolapsed cervical intervertebral disc in patients presenting with myelopathy.

AIM: An alternative form of surgical treatment of prolapsed cervical intervertebral disc in patients presenting with symptoms related to myelopathy is discussed. The treatment involved fixation of the affected spinal segments and aimed at arthrodesis. No direct manipulation or handling of the disc was done. MATERIALS AND METHODS: During the period August 2010 to June 2017, 16 patients presenting with symptoms attributed to myelopathy and diagnosed to have prolapsed cervical intervertebral disc were surgically treated by spinal stabilization. There were 11 males and 5 females and their ages ranged from 20 to 66 years (average: 40.6 years). Apart from clinical and radiological indicators, the number of spinal segments that were stabilized depended on direct observation of facetal morphology, alignment, and stability. Surgery involved distraction-fixation of facets using Goel facet spacer (8 patients), transarticular facetal fixation (5 patients) using screws or a combination of both facetal spacer, and transarticular screws (3 patients). RESULTS: All patients had "remarkable" clinical improvement in the immediate postoperative period as assessed by visual analog scale, Goel's clinical grading, and Japanese Orthopedic Association scores. Follow-up ranged from 3 to 84 months (average: 50 months). The herniated disc regressed or disappeared at follow-up radiological assessment that ranged from 24 h to 3 months after surgery. CONCLUSIONS: Spinal segmental fixation aiming at arthrodesis with or without distraction of facets and without any direct surgical manipulation in the disc space or removal of the prolapsed portion of the disc can be considered in the armamentarium of the surgeon.

Toxin-Induced Experimental Models of Learning and Memory Impairment.

Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-ß are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

Emerging preclinical pharmacological targets for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms.

A novel synthetic compound MCAP suppresses LPS-induced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways.

AIM: To investigate the anti-neuroinflammatory activity of a novel synthetic compound, 7-methylchroman-2-carboxylic acid N-(2-trifluoromethyl) phenylamide (MCAP) against LPS-induced microglial activation in vitro. METHODS: Primary mouse microglia and BV2 microglia cells were exposed to LPS (50 or 100 ng/mL). The expression of iNOS and COX-2, proinflammatory cytokines, NF-κB and p38 MAPK signaling molecules were analyzed by RT-PCR, Western blot and ELISA. The morphological changes of microglia and nuclear translocation of NF-ĸB were visualized using phase contrast and fluorescence microscopy, respectively. RESULTS: Pretreatment with MCAP (0.1, 1, 10 µmol/L) dose-dependently inhibited LPS-induced expression of iNOS and COX-2 in BV2 microglia cells. Similar results were obtained in primary microglia pretreated with MCAP (0.1, 0.5 µmol/L). MCAP dose-dependently abated LPS-induced release of TNF-α, IL-6 and IL-1ß, and mitigated LPS-induced activation of NF-κB by reducing the phosphorylation of IκBα in BV2 microglia cells. Moreover, MCAP attenuated LPS-induced phosphorylation of p38 MAPK, whereas SB203580, a p38 MAPK inhibitor, significantly potentiated MCAP-caused inhibition on the expression of MEF-2 (a transcription factor downstream of p38 MAPK). CONCLUSION: MCAP exerts anti-inflammatory effects in murine microglia in vitro by inhibiting the p38 MAPK and NF-κB signaling pathways and proinflammatory responses. MCAP may be developed as a novel agent for treating diseases involving activated microglial cells.

Synthesis of Pyrene-Fused Pyrazaacenes on Metal Surfaces: Toward One-Dimensional Conjugated Nanostructures.

We investigated the synthesis of one-dimensional nanostructures via Schiff base (imine) formation on three close-packed coinage metal (Au, Ag, and Cu) surfaces under ultrahigh vacuum conditions. We demonstrate the feasibility of forming pyrene-fused pyrazaacene-based oligomers on the Ag(111) surface by thermal annealing of tetraketone and tetraamine molecules, which were designed to afford cyclocondensation products. Direct visualization by scanning tunneling microscopy of reactants, intermediates, and products with submolecular resolution and the analysis of their statistical distribution in dependence of stoichiometry and annealing temperature together with the inspection of complementary X-ray photoelectron spectroscopy signatures provide unique insight in the reaction mechanism, its limitations, and the role of the supporting substrate. In contrast to the reaction on Ag(111), the reactants desorb from the Au(111) surface before reacting, whereas they decompose on the Cu(111) surface during the relevant thermal treatment.

α-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson's disease.

The selective loss of dopaminergic neurons in Parkinson's disease (PD) is associated with microglial activation. Therefore, the importance of early therapeutic intervention to inhibit microglial activation would be an effective strategy to alleviate the progression of PD. α-Asarone, an active compound found in Araceae and Annonaceae plant species has been used to improve various disease conditions including central nervous system disorders. In the present study the in vitro and in vivo therapeutic effects of α-asarone isolated from the rhizome of Acorus gramineus Solander was evaluated on microglia-mediated neuroinflammation and neuroprotection. Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells were used to evaluate in vitro effects. 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of PD was developed to study the neuroprotective effects of α-asarone in vivo. The results indicated that α-asarone significantly attenuated the LPS-stimulated increase in neuroinflammatory responses and suppressed pro-inflammatory cytokine production in BV-2 cells. Mechanistic study revealed that α-asarone inhibited the LPS-stimulated activation via regulation of nuclear factor kappa-B by blocking degradation of inhibitor kappa B-alpha signaling in BV-2 microglial cells. In in vivo studies, MPTP intoxication to mice resulted in brain microglial activation and significant behavioral deficits. Prophylactic treatment with α-asarone suppressed microglial activation and attenuated PD-like behavioral impairments as assessed by the Y-maze and pole tests. Taken together, these data demonstrate that α-asarone is a promising neuroprotective agent that should be further evaluated and developed for future prevention and treatment of microglia-mediated neuroinflammatory conditions including PD.

Promising cannabinoid-based therapies for Parkinson's disease: motor symptoms to neuroprotection.

Parkinson's disease (PD) is a slow insidious neurological disorder characterized by a loss of dopaminergic neurons in the midbrain. Although several recent preclinical advances have proposed to treat PD, there is hardly any clinically proved new therapeutic for its cure. Increasing evidence suggests a prominent modulatory function of the cannabinoid signaling system in the basal ganglia. Hence, use of cannabinoids as a new therapeutic target has been recommended as a promising therapy for PD. The elements of the endocannabinoid system are highly expressed in the neural circuit of basal ganglia wherein they bidirectionally interact with dopaminergic, glutamatergic, and GABAergic signaling systems. As the cannabinoid signaling system undergoes a biphasic pattern of change during progression of PD, it explains the motor inhibition typically observed in patients with PD. Cannabinoid agonists such as WIN-55,212-2 have been demonstrated experimentally as neuroprotective agents in PD, with respect to their ability to suppress excitotoxicity, glial activation, and oxidative injury that causes degeneration of dopaminergic neurons. Additional benefits provided by cannabinoid related compounds including CE-178253, oleoylethanolamide, nabilone and HU-210 have been reported to possess efficacy against bradykinesia and levodopa-induced dyskinesia in PD. Despite promising preclinical studies for PD, use of cannabinoids has not been studied extensively at the clinical level. In this review, we reassess the existing evidence suggesting involvement of the endocannabinoid system in the cause, symptomatology, and treatment of PD. We will try to identify future threads of research that will help in the understanding of the potential therapeutic benefits of the cannabinoid system for treating PD.

Anti-neuroinflammatory effects of DPTP, a novel synthetic clovamide derivative in in vitro and in vivo model of neuroinflammation.

Neuroinflammation is one of the critical pathological mechanisms influencing various neurodegenerative disorders. Most of the neurodegenerative diseases involve over-activation of microglial cells contributing to the demise of neurons. The objective of the current study is to evaluate the anti-inflammatory effect of novel synthetic clovamide derivative on the suppression of microglial activation in an in vitro and in vivo model of neuroinflammation. We have used lipopolysaccharide (LPS) to induce an inflammatory response in murine BV-2 microglial cells. Molecular tools like immunocytochemistry and immunoblotting were used to study the activity of novel synthetic clovamide derivative to inhibit inflammation induced by LPS in microglial cells. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mouse model of neuroinflammation was developed to investigate the anti-neuroinflammatory effects of DPTP [3-(3,4-Dihydroxy-phenyl)-2-[4-(3-trifluoromethylphenyl)-but-2-enoylamino]-propionic acid methyl ester]. DPTP was observed to reduce the proinflammatory response in BV-2 cells induced by LPS. Further investigation revealed that DPTP attenuated phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), which was accompanied by a decrease in nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 microglia. Moreover, prophylactic treatment with DPTP (20mg/kg) for 7 days suppressed MPTP induced glial activation and behavioral impairment. Overall, our findings suggested that, DPTP exerts anti-neuroinflammatory effects against activated microglia in an in vitro and in vivo model and hence might be a promising therapeutic agent for alleviating the evolvement of neurodegenerative diseases associated with microglial activation.

11,11,12,12-Tetracyano-4,5-pyrenoquinodimethanes: air-stable push-pull o-quinodimethanes with S2 fluorescence.

The synthesis and properties of 11,11,12,12-tetracyano-4,5-pyrenoquinodimethanes (4,5-TCNPs), a new family of isolable and air-stable o-quinodimethanes, are reported. The ortho disposition of the dicyanomethane substituents strongly polarizes the pyrene framework to promote broad and intense intramolecular charge-transfer transitions. In addition, spectroscopic studies reveal that 4,5-TCNPs violate Kasha's rule and emit from the S2 level.

EOP, a newly synthesized ethyl pyruvate derivative, attenuates the production of inflammatory mediators via p38, ERK and NF-κB pathways in lipopolysaccharide-activated BV-2 microglial cells.

Microglia-induced neuroinflammation is an important pathological mechanism influencing various neurodegenerative disorders. Excess activation of microglia produces a myriad of proinflammatory mediators that decimate neurons. Hence, therapeutic strategies aimed to suppress the activation of microglia might lead to advancements in the treatment of neurodegenerative diseases. In this study, we synthesized a novel ethyl pyruvate derivative, named EOP (S-ethyl 2-oxopropanethioate) and studied its effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in rat primary microglia and mouse BV-2 microglia. EOP significantly decreased the production of NO, inducible nitric oxide synthase, cyclooxygenase and other proinflammatory cytokines, such as interleukin (IL)-6, IL-1ß and tumor necrosis factor-α, in LPS-stimulated BV-2 microglia. The phosphorylation levels of extracellular regulated kinase, p38 mitogen-activated protein kinase, and nuclear translocation of NF-κB were also inhibited by EOP in LPS-activated BV-2 microglial cells. Overall, our observations indicate that EOP might be a promising therapeutic agent to diminish the development of neurodegenerative diseases associated with microglia activation.

ß-Asarone (cis-2,4,5-trimethoxy-1-allyl phenyl), attenuates pro-inflammatory mediators by inhibiting NF-κB signaling and the JNK pathway in LPS activated BV-2 microglia cells.

Acorus species contains diverse pharmacologically active phytochemicals including α-asarone, ß-asarone, and eugenol. We determined if ß-asarone isolated from Acorus gramineus (AG) Solander would be efficacious in protecting BV-2 microglia cells from lipopolysaccharide (LPS)-induced stress signaling. BV-2 microglial cells were pretreated with an AG ethanol extract (1, 10, and 100 µg/mL) or ß-asarone (10, 50, and 100 µM) prior to exposure to LPS (100 ng/mL). AG and ß-asarone inhibited LPS-induced production of nitric oxide in a dose-dependent manner. The mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 also decreased dose dependently following AG and ß-asarone treatments. Immunostaining and immunoblot studies revealed that ß-asarone also suppressed nuclear factor (NF)-κB activation by blocking IkB degradation. Further mechanistic studies revealed that ß-asarone acted through the JNK/MAPK pathway. Taken together, our findings demonstrate that ß-asarone exhibits anti-inflammatory effects by suppressing the production of pro-inflammatory mediators through NF-κB signaling and the JNK pathways in activated microglial cells and might be developed as a promising candidate to treat various neuroinflammatory diseases.