Drugs for cognitive disorders

2012 ◽  
pp. 1240-1242
Author(s):  
Leslie Iversen
Keyword(s):  
Nervous System ◽  
Animal Models ◽  
Predictive Value ◽  
Animal Studies ◽  
Cognitive Disorders ◽  
New Drugs ◽  
Human Cognition ◽  
International Agreement ◽  
Clinically Significant ◽  
Made In

Cognitive disorders are among the most difficult of all nervous system illnesses to treat as they affect the most complex and least clearly understood aspects of brain function. Animal studies cannot accurately mirror the complexities of human cognition, and there are few, if any, animal models of human cognitive illnesses. As so few drugs have been found to exert clinically significant effects, animal models for testing novel cognition-enhancing agents have unknown predictive value. However, progress has been made in recent years with improved international agreement on the criteria used to approve new cognition-enhancing drugs, and the introduction of new drugs for the treatment of dementia.

scholarly journals Neurobiology of Cancer: Introduction of New Drugs in the Treatment and Prevention of Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 6115
Author(s):  
Boris Mravec
Keyword(s):  
Nervous System ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Clinical Findings ◽  
New Drugs ◽  
Adrenergic Signaling ◽  
Treatment And Prevention ◽  
Oncological Patients ◽  
Cancer Initiation ◽  
Prevention Of Cancer

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.

scholarly journals Inoculum effect of β-lactam antibiotics

2019 ◽  
Vol 74 (10) ◽  
pp. 2825-2843 ◽  
Author(s):  
Justin R Lenhard ◽  
Zackery P Bulman
Keyword(s):  
Clinical Outcomes ◽  
Animal Studies ◽  
Drug Classes ◽  
Clinical Investigations ◽  
Inoculum Effect ◽  
Clinically Significant ◽  
Multiple Pathogens ◽  
Made In

AbstractThe phenomenon of attenuated antibacterial activity at inocula above those utilized for susceptibility testing is referred to as the inoculum effect. Although the inoculum effect has been reported for several decades, it is currently debatable whether the inoculum effect is clinically significant. The aim of the present review was to consolidate currently available evidence to summarize which β-lactam drug classes demonstrate an inoculum effect against specific bacterial pathogens. Review of the literature showed that the majority of studies that evaluated the inoculum effect of β-lactams were in vitro investigations of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Across all five pathogens, cephalosporins consistently displayed observable inoculum effects in vitro, whereas carbapenems were less susceptible to an inoculum effect. A handful of animal studies were available that validated that the in vitro inoculum effect translates into attenuated pharmacodynamics of β-lactams in vivo. Only a few clinical investigations were available and suggested that an in vitro inoculum effect of cefazolin against MSSA may correspond to an increased likeliness of adverse clinical outcomes in patients receiving cefazolin for bacteraemia. The presence of β-lactamase enzymes was the primary mechanism responsible for an inoculum effect, but the observation of an inoculum effect in multiple pathogens lacking β-lactamase enzymes indicates that there are likely multiple mechanisms that may result in an inoculum effect. Further clinical studies are needed to better define whether interventions made in the clinic in response to organisms displaying an in vitro inoculum effect will optimize clinical outcomes.

True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence

2016 ◽  
Vol 30 (7) ◽  
pp. 586-594 ◽  
Author(s):  
Pascal JD Goetghebeur ◽  
Jina E Swartz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Animal Models ◽  
Drug Development ◽  
New Drugs ◽  
Attrition Rate ◽  
Current Evidence ◽  
Therapeutic Area ◽  
Central Nervous System Drug ◽  
Preclinical Research

Central nervous system pharmacological research and development has reached a critical turning point. Patients suffering from disorders afflicting the central nervous system are numerous and command significant attention from the pharmaceutical industry. However, given the numerous failures of promising drugs, many companies are no longer investing in or, indeed, are divesting from this therapeutic area. Central nervous system drug development must change in order to develop effective therapies to treat these patients. Preclinical research is a cornerstone of drug development; however, it is frequently criticised for its lack of predictive validity. Animal models and assays can be shown to be more predictive than reported and, on many occasions, the lack of thorough preclinical testing is potentially to blame for some of the clinical failures. Important factors such as translational aspects, nature of animal models, variances in acute versus chronic dosing, development of add-on therapies and understanding of the full dose–response relationship are too often neglected. Reducing the attrition rate in central nervous system drug development could be achieved by addressing these important questions before novel compounds enter the clinical phase. This review illustrates the relevance of employing these criteria to translational central nervous system research, better to ensure success in developing new drugs in this therapeutic area.

scholarly journals Effects of Mulberry on The Central Nervous System: A Literature Review

2020 ◽  
Vol 19 (2) ◽  
pp. 193-219
Author(s):  
Dao Ngoc Hien Tam ◽  
Nguyen Hai Nam ◽  
Mohamed Tamer Elhady ◽  
Linh Tran ◽  
Osama Gamal Hassan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Animal Models ◽  
Infarct Volume ◽  
Biological Effects ◽  
New Drugs ◽  
In Vivo Studies ◽  
Active Components ◽  
The Central Nervous System

Background: Mulberry, including several species belonging to genus Morus, has been widely used as a traditional medicine for a long time. Extracts and active components of mulberry have many positive neurological and biological effects and can become potential candidates in the search for new drugs for neurological disorders. Objectives: We aimed to systematically review the medical literature for evidence of mulberry effects on the central nervous system. Methods: We conducted a systematic search in nine databases. We included all in vivo studies investigating the effect of mulberry on the central nervous system with no restrictions. Results: We finally included 47 articles for quality synthesis. Our findings showed that mulberry and its components possessed an antioxidant effect, showed a reduction in the cerebral infarct volume after stroke. They also improved the cognitive function, learning process, and reduced memory impairment in many animal models. M. alba and its extracts ameliorated Parkinson's disease-like behaviors, limited the complications of diabetes mellitus on the central nervous system, possessed anti-convulsant, anti-depressive, and anxiolytic effects. Conclusion: Mulberry species proved beneficial to many neurological functions in animal models. The active ingredients of each species, especially M. alba, should be deeper studied for screening potentially candidates for future treatments

Drug Improvement of Cognition : Hope and Reality

1988 ◽  
Vol 3 (S2) ◽  
pp. 115s-123s ◽  
Author(s):  
E.R. Gamzu ◽  
S.I. Gracon
Keyword(s):  
Animal Models ◽  
Cognitive Deficits ◽  
Development Process ◽  
New Drugs ◽  
Poor Correlation ◽  
Disease States ◽  
Number Of Factors ◽  
Basic And Applied Research ◽  
Dose Response Function ◽  
Made In

SummaryRecent research aimed at discovering and developing new drugs for diseases of cognition focuses heavily on Alzheimer’s disease and emphasizes mechanistic/biochemical approaches. Originally, research was based on a pragmatic search for compounds that would protect animals front disruptors of learning and memory. A series of compounds called nootropics do protect animals against these disruptions and offer hope that cognitive deficits may be amenable to pharmacological treatment. However, clinical development of these compounds is complicated by a number of factors. Among these is the poor correlation between animal models of cognitive loss and clinical disease states, a notable exception being the amnesic effects of benzodiazepines. Moreover, the inverted U-shaped dose-response function obtained in animal models and the lack of standard clinical outcome measures further complicate the development process. Tests that are beginning to gain acceptance as “standards” need to be characterized in terms of their validity, variability, and stability. There is a dearth of normative, especially longitudinal, data on cognitive decline. However, the great efforts being made in basic and applied research warrant cautious optimism.

BERLAKU DAN KEABSAHAN PERJANJIAN INTERNASIONAL DALAM PANDANGAN HUKUM INTERNASIONAL

2019 ◽  
Vol 1 (1) ◽  
pp. 95-103
Author(s):  
Komang Sukaniasa
Keyword(s):  
International Law ◽  
International Agreements ◽  
The State ◽  
International Agreement ◽  
International Treaties ◽  
International Treaty ◽  
Binding Force ◽  
International Rights ◽  
Legal Consequences ◽  
Made In

International agreements are agreements between international subjects that give rise to binding obligations in international rights, which can be bilateral or multilateral. Based on these opinions, an understanding can be taken that international treaties are agreements or agreements entered into by two or more countries as subjects of international law that aim to cause certain legal consequences. International agreements, whether ratified or through approval or acceptance or accession, or other methods that are permitted, have the same binding force as ratified international treaties established in the Ratification Law of International Treaties. Once again, it is equally valid and binding on the state. Therefore, the authors consider that the position of international treaties are not made in the form of the Ratification Act of the International Agreement but are binding and apply to Indonesia. Then Damos Dumoli Agusman argues that ratification originates from the conception of international treaty law which is interpreted as an act of confirmation from a country of the legal acts of its envoys or representatives who have signed an agreement as a sign of agreement to be bound by the agreement.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

scholarly journals Animal Models of Autosomal Recessive Parkinsonism

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 812
Author(s):  
Guendalina Bastioli ◽  
Maria Regoni ◽  
Federico Cazzaniga ◽  
Chiara Maria Giulia De Luca ◽  
Edoardo Bistaffa ◽  
...  
Keyword(s):  
Animal Models ◽  
Sleep Disturbances ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Cognitive Disorders ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Current Status ◽  
Unknown Etiology ◽  
Neuron Death

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. The neuropathological hallmark of the disease is the loss of dopamine neurons of the substantia nigra pars compacta. The clinical manifestations of PD are bradykinesia, rigidity, resting tremors and postural instability. PD patients often display non-motor symptoms such as depression, anxiety, weakness, sleep disturbances and cognitive disorders. Although, in 90% of cases, PD has a sporadic onset of unknown etiology, highly penetrant rare genetic mutations in many genes have been linked with typical familial PD. Understanding the mechanisms behind the DA neuron death in these Mendelian forms may help to illuminate the pathogenesis of DA neuron degeneration in the more common forms of PD. A key step in the identification of the molecular pathways underlying DA neuron death, and in the development of therapeutic strategies, is the creation and characterization of animal models that faithfully recapitulate the human disease. In this review, we outline the current status of PD modeling using mouse, rat and non-mammalian models, focusing on animal models for autosomal recessive PD.

scholarly journals Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Jianling Ji ◽  
Kristiyana Kaneva ◽  
Matthew C Hiemenz ◽  
Girish Dhall ◽  
Tom Belle Davidson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Utility ◽  
Adolescent And Young Adult ◽  
Cns Tumors ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
Clinically Significant

Abstract Background Recent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity. Methods OncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146/222) of cases. Results NGS demonstrated clinically significant alterations in 66% (147/222) of cases. Diagnostic markers were identified in 62% (138/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49/222) and 18% (41/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome. Conclusions Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

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