Treatment Of Nervous System Disorders Research Articles

Neural Tracing Protein-Functionalized Nanoparticles Capable of Fast Retrograde Axonal Transport in Live Neurons.

Neural tracing proteins like horseradish peroxidase-conjugated wheat germ agglutinin (WGA-HRP) can target the central nervous system (CNS) through anatomic retrograde transport without crossing the blood-brain barrier (BBB). Conjugating WGA-HRP to nanoparticles may enable the creation of BBB-bypassing nanomedicine. Microfluidics and two-photon confocal microscopy is applied to screen nanocarriers for transport efficacy and gain mechanistic insights into their interactions with neurons. Protein modification of gold nanoparticles alters their cellular uptake at the axonal terminal and activates fast retrograde transport. Trajectory analysis of individual endosomes carrying the nanoparticles reveals a run-and-pause pattern along the axon with endosomes carrying WGA-HRP-conjugated gold nanoparticles exhibiting longer run duration and faster instantaneous velocity than those carrying nonconjugated nanoparticles. The results offer a mechanistic explanation of the different axonal transport dynamics as well as a cell-based functional assay of neuron-targeted nanoparticles with the goal of developing BBB-bypassing nanomedicine for the treatment of nervous system disorders.

Sweet basil (Ocimum basilicum) leaf and seed extracts alleviate neuronal dysfunction in aluminum chloride-induced neurotoxicity in Drosophila melanogaster Meigen model

Ocimum basilicum is an important medicinal plant and culinary herb generally known as sweet basil (SB). These plants are effective radical scavengers, that have been employed in treatment of nervous system disorders, and thus, could be beneficial for the management of neurodegenerative diseases (NDs). Current clinical treatments for NDs present several side effects, therefore, there is need to develop new treatments that can mitigate these deadly diseases. Hence, this study investigated the neuroprotective activities of SB leaf and seed in aluminum chloride (AlCl3)-induced toxicity in Drosophila melanogaster. HPLC characterization of the leaves and seeds were carried out. AlCl3-diet was used to induce neurodegeneration and treated flies received SB leaf and seed extracts-supplemented diet. Survival and locomotor performance activities/levels of oxidative biomarkers [reactive oxygen species (ROS), thiobarbituric acid reactive species (TBARS), total thiol, catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST)], enzymes linked with neurodegeneration (acetylcholinesterase (AChE) and monoamine oxidase (MAO)) were investigated. SB leaf had significantly (p < 0.05) higher polyphenol contents; gallic acid and P-coumaric acid were the most abundant polyphenol in the leaf and seed respectively. Percentage survival and locomotor rates, level/activities of total thiol, catalase, SOD and GST were significantly (p < 0.05) reduced while ROS, TBARS, AChE and MAO activities were significantly (p < 0.05) increased in AlCl3-diet-fed flies. Treatment with SB leaf and seed diet lessened these observed impairments. However, SB leaf had better neuroprotective activities that could be related to the observed higher phenolic constituents. Hence, SB leaf diet may offer improved therapeutic effect in NDs.

Zinc and Central Nervous System Disorders.

Zinc (Zn2+) is the second most abundant necessary trace element in the human body, exerting a critical role in many physiological processes such as cellular proliferation, transcription, apoptosis, growth, immunity, and wound healing. It is an essential catalyst ion for many enzymes and transcription factors. The maintenance of Zn2+ homeostasis is essential for the central nervous system, in which Zn2+ is abundantly distributed and accumulates in presynaptic vesicles. Synaptic Zn2+ is necessary for neural transmission, playing a pivotal role in neurogenesis, cognition, memory, and learning. Emerging data suggest that disruption of Zn2+ homeostasis is associated with several central nervous system disorders including Alzheimer's disease, depression, Parkinson's disease, multiple sclerosis, schizophrenia, epilepsy, and traumatic brain injury. Here, we reviewed the correlation between Zn2+ and these central nervous system disorders. The potential mechanisms were also included. We hope that this review can provide new clues for the prevention and treatment of nervous system disorders.

(2-Cyclohexyl-1-methylpropyl) cyclohexane isolated from garlic extract exhibits antidepressant-like activity: extraction, docking, drug-like properties, molecular dynamics simulations and MM/GBSA studies

Depressive disorders are among most common psychiatric diseases and second most common form of psychiatric illness globally. Commonly available chemical drugs used for treatment of nervous system disorders exert undesirable effects. Therefore, there is a growing need towards exploring novel antidepressants of herbal origin. Earlier, the antidepressant effect of methanolic extract of garlic has been shown. In this study, the ethanolic extract of garlic was prepared and chemically analysed using Gas Chromatography – Mass Spectrometry (GC-MS) screening. A total of 35 compounds were found to be present, which might act as antidepressant. Using computational analyses, these compounds were screened as potential inhibitors (selective serotonin reuptake inhibitor (SSRI)) against serotonin transporter (SERT)/leucine receptor (LEUT). In silico docking studies and other physicochemical, bioactivity and ADMET studies resulted in the selection of compound 1 ((2-Cyclohexyl-1-methylpropyl) cyclohexane) as potential SSRI (binding energy −8.1 kcal/mol) compared to known reference SSRI fluoxetine (binding energy −8.0 kcal/mol). Analysis of conformational stability, residue flexibility, compactness, binding interactions, solvent accessible surface area (SASA), dynamic correlation, and binding free energy predicted from molecular mechanics (MD) with generalised Born and surface area solvation (MM/GBSA) studies revealed formation of a more stable SSRI like complex with compound 1 having strong inhibitory interaction compared to known SSRI fluoxetine/reference complex. Thus, compound 1 may act as an active SSRI leading to discovery of potential antidepressant drug. Communicated by Ramaswamy H. Sarma

The Effective Components, Core Targets, and Key Pathways of Ginseng against Alzheimer's Disease.

Panax ginseng C. A. Mey (ginseng) is a traditional Chinese medicinal herb used for the treatment of nervous system disorders, such as Alzheimer's disease (AD). However, the pharmacological mechanisms of ginseng involved in AD have not been systematically investigated. Here, a network pharmacology approach was adopted to explore the effective components, core targets, and key pathways of ginseng against AD. TCMSP database was used to screen the active ingredients of ginseng. Prediction of the targets of ginseng and AD-related genes was performed using online public databases. "Compound-Target," "Compound-Target-Disease," "Protein-Protein Interaction (PPI)," "Compound-Target-Pathway," and "Compound-Target-GO-Pathway" networks were constructed with Cytoscape 3.7.2 software. Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed by using the DAVID database. A total of 22 bioactive compounds were identified from ginseng, and 481 targets of ginseng and 763 AD-related targets were obtained from public databases. The PPI network screened out 19 hub genes of ginseng against AD. According to GO function enrichment, ginseng influenced cell proliferation, death, the nitric oxide biosynthetic process, hypoxia response, and synaptic transmission. Neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling, cAMP signaling, FoxO signaling, Ras signaling, and PI3K-AKT signaling were among the most key regulatory pathways. The compound-target-GO-route network found EGFR, MAPK1, MAPK14, AKT1, CASP3, and PRKACA as key genes, with PI3K-AKT signaling being the most important pathway for ginseng's anti-AD activity. Ginseng exerts neuroprotective effects in AD patients through multicomponent, multitarget, and multipathway modes, providing novel insight into the pharmacological and experimental research on ginseng against AD.

A review for the pharmacological effects of paeoniflorin in the nervous system.

Paeoniflorin, a terpenoid glycoside compound extracted from Paeonia lactiflora Pall, shows preventive and therapeutic effects in various types of nervous system disorders. However, to date, no comprehensive knowledge on the pharmacological effects of paeoniflorin on the nervous system is available online. Clarification of this issue may be useful for the development of paeoniflorin as a new drug for the treatment of nervous system disorders. To this end, the authors summarize the pharmacological aspects of paeoniflorin and its possible mechanisms, such as restoration of mitochondrial function; inhibition of neuroinflammation, oxidative stress, and cellular apoptosis; activation of adenosine A1 receptor, cAMP response element-binding protein (CREB) and extracellular signal-regulated kinase 1/2 (ERK1/2); or enhancement of brain-derived neurotrophic factor and serotonin function, in the prevention of disorders such as cerebral ischemia, subarachnoid hemorrhage, vascular dementia, Alzheimer’s disease, Parkinson’s disease, depression, post-traumatic syndrome disorder, and epilepsy, by reviewing the previously published literature.

Ketapang (Terminalia catappa L.): Potential utilization as foodstuffs and traditional medicine

Indonesian local people use Terminalia catappa L. (TC) as a shade, traditional medicine and vegetables. This study aims to examine the utilization and bioactivity of TC. The research method uses online library research, especially from Google Scholar, using the keywords TC, uses TC and bioactivity of TC. The information obtained was synthesized so as to explain the botany and the use of TC in a comprehensive manner. The TC leaves and seeds can be used as food because they are rich in nutrients and mineral salts. TC seeds are carbohydrates, fats, saturated fatty acids, unsaturated fatty acids and mineral salts in the form of Calcium, Iron and Zinc. In traditional medicine, TC has been used to treat hypertension, hepatitis, colitis, depression and anti-aging. The bioactivity of TC such as anti-diabetes mellitus, anti-microbial, antioxidant, anti-neurodegenerative, anti-aging, hepatoprotective, anti-cancer, anti-depressant, anti-hypertensive, anti-ulcer and immunomodulatory activities. The potential of TC as an anti-neurodegenerative and anti-stress needs to be studied further as a new alternative in the treatment of nervous system disorders as well as a source of unsaturated fatty acids.

Pharmacological Actions of Myricetin in the Nervous System: A Comprehensive Review of Preclinical Studies in Animals and Cell Models.

Myricetin is a natural flavonoid extracted from a variety of plants, such as medicinal herbs, vegetables, berries, and tea leaves. A growing body of evidence has reported that myricetin supplementation display therapeutic activities in a lot of nervous system disorders, such as cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, epilepsy, and glioblastoma. Myricetin supplementation can also protect against pathological changes and behavioral impairment induced by multiple sclerosis and chronic stress. On the basis of these pharmacological actions, myricetin could be developed as a potential drug for the prevention and/or treatment of nervous system disorders. Mechanistic studies have shown that inhibition of oxidative stress, cellular apoptosis, and neuroinflammatory response are common mechanisms for the neuroprotective actions of myricetin. Other mechanisms, including the activation of the nuclear factor E2-related factor 2 (Nrf2), extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (Akt), cyclic adenosine monophosphate-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) signaling, inhibition of intracellular Ca2+ increase, inhibition of c-Jun N-terminal kinase (JNK)-p38 activation, and suppression of mutant protein aggregation, may also mediate the neuroprotective effects of myricetin. Furthermore, myricetin treatment has been shown to promote the activation of the inhibitory neurons in the hypothalamic paraventricular nucleus, which subsequently produces anti-epilepsy effects. In this review, we make a comprehensive understanding about the pharmacological effects of myricetin in the nervous system, aiming to push the development of myricetin as a novel drug for the treatment of nervous system disorders.

Discovering Geometry in Data Arrays.

Modern technologies produce a deluge of complicated data. In neuroscience, for example, minimally invasive experimental methods can take recordings of large populations of neurons at high resolution under a multitude of conditions. Such data arrays possess non-trivial interdependencies along each of their axes. Insights into these data arrays may lay the foundations of advanced treatments for nervous system disorders. The potential impacts of such data, however, will not be fully realized unless the techniques for analyzing them keep pace. Specifically, there is an urgent, growing need for methods for estimating the low-dimensional structure and geometry in big and noisy data arrays. This article reviews a framework for identifying complicated underlying patterns in such data and also recounts the key role that the Department of Energy Computational Sciences Graduate Fellowship played in setting the stage for this work to be done by the author.

Descriptive analysis of adverse drug reaction reports in children and adolescents from Germany: frequently reported reactions and suspected drugs

BackgroundAdverse drug reactions (ADRs) in the pediatric population may differ in types and frequencies compared to other populations. Respective studies analyzing ADR reports referring to children have already been performed for certain countries. However, differences in drug prescriptions, among others, complicate the transferability of the results from other countries to Germany or were rarely considered. Hence, the first aim of our study was to analyze the drugs and ADRs reported most frequently in ADR reports from Germany referring to children contained in the European ADR database (EudraVigilance). The second aim was to set the number of ADR reports in relation to the number of drug prescriptions. These were provided by the Research Institute for Ambulatory Health Care in Germany.MethodsFor patients aged 0–17 years 20,854 spontaneous ADR reports were received between 01/01/2000–28/2/2019. The drugs and ADRs reported most frequently were identified. Stratified analyses with regard to age, sex and drugs used “off-label” were performed. Reporting rates (number of ADR reports/number of drug prescriptions) were calculated.ResultsMethylphenidate (5.5%), ibuprofen (2.3%), and palivizumab (2.0%) were most frequently reported as suspected. If related to the number of drug prescriptions, the ranking changed (palivizumab, methylphenidate, ibuprofen). Irrespective of the applied drugs, vomiting (5.4%), urticaria (4.6%) and dyspnea (4.2%) were the ADRs reported most frequently. For children aged 0–1 year, drugs for the treatment of nervous system disorders and foetal exposure during pregnancy were most commonly reported. In contrast, methylphenidate ranked first in children older than 6 years and referred 3.5 times more often to males compared to females. If age- and sex-specific exposure was considered, more ADR reports for methylphenidate referred to children 4–6 years and females 13–17 years. Drugs for the treatment of nervous system disorders ranked first among “off-label” ADR reports.ConclusionsOur analysis underlines the importance of putting the number of ADR reports of a drug in context with its prescriptions. Additionally, differences in age- and sex-stratified analysis were observed which may be associated with age- and sex-specific diseases and, thus, drug exposure. The drugs most frequently included in “off-label” ADR reports differed from those most often used according to literature.

Bidentatide, a Novel Plant Peptide Derived from Achyranthes bidentata Blume: Isolation, Characterization, and Neuroprotection through Inhibition of NR2B-Containing NMDA Receptors.

Increasing attention is being focused on the use of polypeptide-based N-methyl-d-aspartate (NMDA) receptor antagonists for the treatment of nervous system disorders. In our study on Achyranthes bidentata Blume, we identified an NMDA receptor subtype 2B (NR2B) antagonist that exerts distinct neuroprotective actions. This antagonist is a 33 amino acid peptide, named bidentatide, which contains three disulfide bridges that form a cysteine knot motif. We determined the neuroactive potential of bidentatide by evaluating its in vitro effects against NMDA-mediated excitotoxicity. The results showed that pretreating primary cultured hippocampal neurons with bidentatide prevented NMDA-induced cell death and apoptosis via multiple mechanisms that involved intracellular Ca2+ inhibition, NMDA current inhibition, and apoptosis-related protein expression regulation. These mechanisms were all dependent on bidentatide-induced inhibitory regulation of NR2B-containing NMDA receptors; thus, bidentatide may contribute to the development of neuroprotective agents that would likely possess the high selectivity and safety profiles inherent in peptide drugs.

Neurogenic and Neuroprotective Potential of Stem/Stromal Cells Derived from Adipose Tissue

Currently, the number of stem-cell based experimental therapies in neurological injuries and neurodegenerative disorders has been massively increasing. Despite the fact that we still have not obtained strong evidence of mesenchymal stem/stromal cells’ neurogenic effectiveness in vivo, research may need to focus on more appropriate sources that result in more therapeutically promising cell populations. In this study, we used dedifferentiated fat cells (DFAT) that are proven to demonstrate more pluripotent abilities in comparison with standard adipose stromal cells (ASCs). We used the ceiling culture method to establish DFAT cells and to optimize culture conditions with the use of a physioxic environment (5% O2). We also performed neural differentiation tests and assessed the neurogenic and neuroprotective capability of both DFAT cells and ASCs. Our results show that DFAT cells may have a better ability to differentiate into oligodendrocytes, astrocytes, and neuron-like cells, both in culture supplemented with N21 and in co-culture with oxygen–glucose-deprived (OGD) hippocampal organotypic slice culture (OHC) in comparison with ASCs. Results also show that DFAT cells have a different secretory profile than ASCs after contact with injured tissue. In conclusion, DFAT cells constitute a distinct subpopulation and may be an alternative source in cell therapy for the treatment of nervous system disorders.

Sparse coding classification and cepstral singular value for cognitive workload estimation

Cognitive workload estimation (CLE) is an interesting but challenging task with applications ranging from diagnosis and treatment of nervous system disorders to brain computer interface. The performance of CLE is usually affected by individual differences and recording noises. Noise-robustness paradigms that are independent of small variations may offer a solution to this challenge. Hence, a new CLE system based on the novel application of integrated singular value decomposition (SVD), cepstrum analysis and sparse non-negative least-square coding method was proposed. It extracted both of algebraic and harmonic information.The method was tested using electrocardiogram signals of 45 subjects while performing an arithmetic task with different levels of difficulty. It effectively estimated the workload levels using a small number of features with an average accuracy of 91%. The Hankel matrix-based SVD performed as well as non-overlapping matrix. Furthermore, significant improvement in the performance was observed as compared to conventional classifiers and features.

Cerebrospinal fluid replacement solutions promote neuroglia migratory behaviors and spinal explant outgrowth in microfluidic culture.

Disorders of the nervous system (NS) impact millions of adults, worldwide, as a consequence of traumatic injury, genetic illness, or chronic health conditions. Contemporary studies have begun to incorporate neuroglia into emerging NS therapies to harness the regenerative potential of glial-mediated synapses in the brain and spinal cord. However, the role of cerebrospinal fluid (CSF) that surrounds neuroglia and interfaces with their associated synapses remains only partially explored. The flow of CSF within subarachnoid spaces (SAS) circulates essential polypeptides, metabolites, and growth factors that directly impact neural response and recovery via signaling with healthy glia. Despite the availability of artificial CSF solutions used in neurosurgery and NS treatments, tissue engineering projects continue to use cell culture media, such as Neurobasal (NB) and Dulbecco's Modified Eagle Medium (DMEM), for development and characterization of many transplantable cells, matrixes, and integrated cellular systems. The current study examined in vitro behaviors of glial Schwann cells (ShC) and spinal cord explants (SCE) within a CSF replacement solution, Elliott's B Solution (EBS), used widely in the treatment of NS disorders. Our tests used EBS to create defined chemical microenvironments of extracellular factors within a glial line (gLL) microfluidic device, previously described by our group. The gLL is comparable in scale to the in vivo SAS that envelopes endogenous CSF and enables molecular transport via mechanisms of convective diffusion. Our results illustrate that EBS solutions facilitate ShC survival, morphology, and proliferation similar to those measured in traditional DMEM, and additionally support glial chemotactic behaviors in response to brain-derived growth factor (BDNF). Our data indicates that ShC undergo significant chemotaxis toward high and low concentration gradients of BDNF with statistical differences between gradients formed within diluents of EBS and DMEM solutions. Moreover, SCE cultured with EBS solutions facilitated measurement of neurite explant extension commensurate with reported in vivo measurements. This data highlights the translational significance and advantages of incorporating CSF replacement fluids to interrogate cellular behaviors and advance regenerative NS therapies.

Brain-derived neurotrophic factor as a potential therapeutic tool in the treatment of nervous system disorders

Brain-derived neurotrophic factor (BDNF) plays an important role in the proper functioning of the nervous system. It regulates the growth and survival of nerve cells, and is crucial in processes related to the memory, learning and synaptic plasticity. Abnormalities related to the distribution and secretion of BDNF protein accompany many diseases of the nervous system, in the course of which a significant decrease in BDNF level in the brain is observed. Impairments of BDNF transport may occur, for example, in the event of a single nucleotide polymorphism in the Bdnf (Val66Met) coding gene or due to the dysfunctions of the proteins involved in intracellular transport, such as huntingtin (HTT), huntingtin-associated protein 1 (HAP1), carboxypeptidase E (CPE) or sortilin 1 (SORT1). One of the therapeutic goals in the treatment of diseases of the central nervous system may be the regulation of expression and secretion of BDNF protein by nerve cells. Potential therapeutic strategies are based on direct injection of the protein into the specific region of the brain, the use of viral vectors expressing the Bdnf gene, transplantation of BDNF-producing cells, the use of substances of natural origin that stimulate the cells of the central nervous system for BDNF production, or the use of molecules activating the main receptor for BDNF – tyrosine receptor kinase B (TrkB). In addition, an appropriate lifestyle that promotes physical activity helps to increase BDNF level in the body. This paper summarizes the current knowledge about the biological role of BDNF protein and proteins involved in intracellular transport of this neurotrophin. Moreover, it presents contemporary research trends to develop therapeutic methods, leading to an increase in the level of BDNF protein in the brain.

Protective Effect of Schisandra chinensis Extract Against Ethanol-Induced Gastric Ulcers in Mice by Promoting Anti-inflammatory and Mucosal Defense Mechanisms

Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a common Chinese traditional medicine for the treatment of nervous system disorders and cardiovascular diseases. However, little is known about its efficacy in treating gastrointestinal diseases. In the present study, the protective effect of the ethanol extract of S. chinensis against ethanol-induced acute gastric lesions was investigated in mice. Furthermore, we developed a method based on high-performance liquid chromatography for the quantification of bioactive lignans with a dibenzocyclooctadiene skeleton. The ethanol extract of S. chinensis significantly decreased the ulcer index, sheltered mucosa from lesions, increased levels of superoxide dismutase, decreased malondialdehyde levels, and downregulated plasma levels of tumor necrosis factor-α and interleukin-1β. Our findings demonstrated the gastroprotective properties of the ethanol extract of S. chinensis.

The Neuropeptide Kyotorphin as a Possible Biomarker and Neuroprotective Agent in Alzheimer’s Disease

Summary Alzheimer’s disease (AD) is an age-related neurodegenerative disorder clinically characterized by memory impairment, disorientation, cognitive deficits, and behavioral disturbances. The neuropathological features are amyloid plaques containing aggregated amyloid-beta (Aβ) peptide, neurofibrillary tangles composed of the hyperphosphorylated form of the microtubule protein tau (HP-tau), and loss of neurons and synapses in the brain. There are no effective strategies for the prevention or treatment of the disease, leading to an increased need for AD biomarkers to improve early detection, accurate diagnosis, and accelerate drug development in this field. Recently, increasing attention has been dedicated to neuropeptides in searching for new drug targets in the treatment of nervous system disorders. Available data suggest that many neuropeptides may be associated with the pathophysiology and potential therapy of AD because of their wide distribution in brain areas responsible for learning and memory processes and their predominately neuroprotective actions. This short review aimed to briefly describe the neuropathology of AD and summarize the data related to one of its recently proposed biomarker - kyotorphin (KTP) neuropeptide. Our previous experiments showed moderate and selective protective effects of KTP against the late consequences of the intracerebroventricular streptozotocin-induced AD model.

Prediction of Neuropeptides from Sequence Information Using Ensemble Classifier and Hybrid Features.

As hormones in the endocrine system and neurotransmitters in the immune system, neuropeptides (NPs) provide many opportunities for the discovery of new drugs and targets for nervous system disorders. In spite of their importance in the hormonal regulations and immune responses, the bioinformatics predictor for the identification of NPs is lacking. In this study, we develop a predictor for the identification of NPs, named PredNeuroP, based on a two-layer stacking method. In this ensemble predictor, 45 models are introduced as base-learners by combining nine feature descriptors with five machine learning algorithms. Then, we select eight base-learners referring to the sum of accuracy and Pearson correlation coefficient of base-learner pairs on the first-layer learning. On the second-layer learning, the outputs of these advisable base-learners are imported into logistic regression classifier to train the final model, and the outputs are the final predicting results. The accuracy of PredNeuroP is 0.893 and 0.872 on the training and test data sets, respectively. The consistent performance on these data sets approves the practicability of our predictor. Therefore, we expect that PredNeuroP would provide an important advancement in the discovery of NPs as new drugs for the treatment of nervous system disorders. The data sets and Python code are available at https://github.com/xialab-ahu/PredNeuroP.

Frequent Adverse Drug Reactions, and Medication Groups under Suspicion.

The adverse drug reaction database of the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) contains reports of suspected adverse drug reactions (ADRs) that are spon- taneously submitted by physicians, pharmacists, or patients. The aim of the present study was a descriptive analysis of all of these spontaneous reports. 345 662 spontaneously submitted reports were analyzed with respect to the number of reports per year, the sources of the reports, demographic variables, the most commonly reported ADRs, and the drug classes most commonly suspected. The number of reports submitted spontaneously each year has grown steadily since 1978. At the least detailed level of analysis, "drugs for the treatment of nervous system disorders" were the most common class of drugs under suspicion of causing the reported adverse drug reactions (23.1%). In a more detailed analysis by therapeutic subgroup, the three subgroups most commonly reported as suspected of causing side effects were antithrombotic agents, systemic antibiotics, and psycholeptics-causing thrombocytopenia, diarrhea, and drug dependency as the most frequently reported ADRs, respectively. The order of drug classes most commonly causing ADRs differed markedly between the physicians' reports (diazepines, fluoroquinolones, heparins) and the patients' reports (interferons, anti- thrombotic drugs, selective immunosuppressant drugs). Patients more commonly reported subjectively perceived ADRs, while physicians more commonly reported findings or diagnoses that require medical expertise. The increasing number of spontaneous reports is mainly due to reports forwarded from pharmaceutical companies to the BfArM. This, in turn, is probably a result of increasingly strict legal reporting requirements in Germany. The detected differences between physicians' and patients' ADR reports can be taken to indicate that patients should be more specifically informed and questioned about potential ADRs. By reporting adverse drug reactions, physicians may improve drug safety.

Meta-Analysis of the Effects of Xingnaojing Injection on Consciousness Disturbance.

Xingnaojing (XNJ) is commonly extracted from Angongniuhuang, a classic Chinese emergency prescription, and widely used in the treatment of nervous system disorders including consciousness disturbance in China.To evaluate the beneficial and adverse effects of XNJ injection, on consciousness disturbance.Seven major electronic databases were searched to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ alone or combined with Western medicine in treating consciousness disturbance caused by conditions such as high fever, poisoning, and stroke. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, and analyzed using the RevMan 5.3.0 software.Seventeen randomized controlled trials on XNJ were included in this study and the trials generally showed low methodological quality. The results revealed that XNJ alone or in combination with other medicines and adjuvant methods had a positive effect on patients with fever-, poisoning-, and stroke-induced coma.XNJ effectively treated consciousness disturbances that were caused by high fever, poisoning, or stroke.