Identifying and Understanding Seizure Liability in Drug Development.

Seizures are complex electrophysiological disturbances affecting one or more populations of brain neurons. Seizures following test article (TA) exposure pose significant challenges in drug development. This paper considers the diverse neurological manifestations, mechanisms, and functional and structural assessments needed to investigate TA-related seizure liabilities, with a particular focus on nonclinical species.

The Role of Neuropathology Evaluation in the Nonclinical Assessment of Seizure Liability.

Test article (TA)-induced seizures represent a major safety concern in drug development. Seizures (altered brain wave [electrophysiological] patterns) present clinically as abnormal consciousness with or without tonic/clonic convulsions (where "tonic" = stiffening and "clonic" = involuntary rhythmical movements). Neuropathological findings following seizures may be detected using many methods.

Practical considerations in the establishment of psychedelic research programs.

Rationale: There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs.

Cephalometrics of Pharyngeal Airway Space in Lebanese Adults.

. The upper airway space is significant in orthodontic diagnosis and treatment planning. The objectives of this study are to assess the dimensions of soft tissue elements of the upper pharyngeal space and evaluate potential correlations with modifying variables such as gender, skeletal class, and anthropometric parameters.

Craniofacial characteristics in the sagittal dimension: A cephalometric study in Lebanese young adults.

Objectives: The purpose of this study was to assess the sagittal cephalometric characteristics of young adult Lebanese individuals and assess gender-related differences.

Materials And Methods: Conventional lateral cephalograms were obtained from 117 subjects. Eight linear/angular measurements combining sagittal parameters selected form McNamara and Steiner analyses were recorded.

Safety pharmacology investigations on the nervous system: An industry survey.

The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ('CNS') drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1000 employees).

EEG in non-clinical drug safety assessments: Current and emerging considerations.

Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in preclinical safety studies, pre-dose or post-dose EEG assessments are not. Industry practices as they relate to preclinical seizure liability and sleep assessments are not well characterized and the extent of preclinical EEG testing varies between organizations.

'What's in the NIDDK CDR?'--public query tools for the NIDDK central data repository.

The National Institute of Diabetes and Digestive Disease (NIDDK) Central Data Repository (CDR) is a web-enabled resource available to researchers and the general public. The CDR warehouses clinical data and study documentation from NIDDK funded research, including such landmark studies as The Diabetes Control and Complications Trial (DCCT, 1983-93) and the Epidemiology of Diabetes Interventions and Complications (EDIC, 1994-present) follow-up study which has been ongoing for more than 20 years. The CDR also houses data from over 7 million biospecimens representing 2 million subjects.

Cannabinoid discrimination and antagonism by CB(1) neutral and inverse agonist antagonists.

Cannabinoid receptor 1 (CB(1)) inverse agonists (e.g., rimonabant) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications.

The NIDDK Central Repository at 8 years--ambition, revision, use and impact.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository makes data and biospecimens from NIDDK-funded research available to the broader scientific community. It thereby facilitates: the testing of new hypotheses without new data or biospecimen collection; pooling data across several studies to increase statistical power; and informative genetic analyses using the Repository's well-curated phenotypic data. This article describes the initial database plan for the Repository and its revision using a simpler model.

Relative potency and effectiveness of flunitrazepam, ethanol, and beta-CCE for disrupting the acquisition and retention of response sequences in rats.

Despite the knowledge that gamma-aminobutyric acid(A) modulators can affect learning and memory, their capacity for disrupting each of these complex processes is rarely compared, and often mistakenly assumed to occur with identical potency. For these reasons, the effects of flunitrazepam (0.056-3.

Interplay of mechanical loading and growth factors in the mandibular condyle.

The mandibular condyle is an important growth site in the developing mandible. The growth of the condyle is known to be highly adaptable to functional factors. This property is exploited in orthodontics for the treatment of class II malocclusions and mandibular asymmetries.

Some effects of CB1 antagonists with inverse agonist and neutral biochemical properties.

The CB1 inverse agonist/antagonist SR141716A recently has been introduced for the management of obesity (rimonabant; Acomplia) and appears to have beneficial effects. However, its utility may be hampered in some individuals by adverse effects including nausea or emesis or by mood depression. The recent development of biochemically 'neutral' antagonists such as AM4113 (Sink et al.

Evaluation of cannabinoid agonists using punished responding and midazolam discrimination procedures in squirrel monkeys.

Rationale: Clinical studies have suggested that marijuana and nabilone have anxiolytic effects in humans, yet studies of anxiolytic-like effects of cannabinoid agonists in mice and rats have yielded mixed results.

Objective: The purpose of the present study was to compare the effects of cannabinoid agonists and clinically used anxiolytic drugs in monkeys using punished responding and midazolam discrimination procedures.

Methods: Monkeys were trained to discriminate an i.

[Prevention and treatment of dento-maxillary discrepancy].

The many clinical and radiological signs of arch length discrepancy simplify the practitioner's task of diagnosing it early. When they need to deal with insufficient room in the dental arch, orthodontists have available to them a large variety of therapeutic possibilities that require relatively little cooperation from young patients and that often work quickly to correct beginning malocclusions in the mixed dentition or that prevent them from worsening. Orthodontists decide whether to use space maintainers, increase arch length, or embark on a program of serial extraction depending upon the type of disorder, its severity, and its etiology.

Regulatory effects of FGF-2 on the growth of mandibular condyles and femoral heads from newborn rats.

The secondary cartilage of the mandibular condyle is considered to be adaptive to functional factors. In the last decades, growth factors have also been shown to be potent regulators of cartilage metabolism. Moreover, it has been suggested that growth factors may differentially regulate the growth of primary and secondary cartilages.

Growth regulation of the rat mandibular condyle and femoral head by transforming growth factor-{beta}1, fibroblast growth factor-2 and insulin-like growth factor-I.

The mandibular condyle is a major growth site and is known to adapt to functional factors. Numerous studies have been performed on the effects of growth factors on the metabolism of primary cartilages, but only a few investigations have examined their action on primary and secondary cartilages. Therefore, the purpose of this study was to compare the effects of insulin-like growth factor-I (IGF-I), transforming growth factor-beta(1) (TGF-beta(1)), and fibroblast growth factor-2 (FGF-2) on the growth of secondary cartilage from the mandibular condyle and primary cartilage from the femoral head of new-born rats.

Effects of MDMA administration on scopolamine-induced disruptions of learning and performance in rats.

Functional deficits following short-course high-dose administration of 3,4-methylenedioxymethamphetamine (MDMA) have been difficult to characterize despite evidence indicating that MDMA is neurotoxic in several species. Therefore, the present research used rats trained to respond under a complex behavioral procedure (i.e.

Primary and secondary cartilages of the neonatal rat: the femoral head and the mandibular condyle.

Primary and secondary cartilages differ in embryonic origin and in histological organization, and are generally considered to have a different mode of growth. However, few studies have directly compared the two types of cartilage of the same animal at the same age. Therefore, we analysed several histological and biochemical differences between secondary cartilage of the mandibular condyle and primary cartilage of the femoral head of 4-d-old rats.

Growth stimulation of mandibular condyles and femoral heads of newborn rats by IGF-I.

Primary and secondary cartilage differ in embryonic origin and are generally considered to have a different mode of growth. However, few experimental studies exist that directly compare the two types of cartilage and their growth regulation. The regulation of cartilage growth is a complex mechanism involving growth factors like insulin-like growth factor-I (IGF-I).

[Pre- and post-surgical orthodontic objectives and orthodontic preparation].

Orthodontics in combination with orthognathic surgery is a possibility today for correcting sagittal, vertical and transversal dysmorphosis. To do this, orthodontic preparation before surgery is necessary. In the sagittal plane, dental compensations should be removed.

[Indications for orthognathic surgery, the limitations of orthodontics and of surgery].

The different sagittal, vertical or transversal skeletal dysmorphosis can be treated with orthodontic or orthopaedic appliances. Certain limits of treatment will be due to the age of the patient, the importance of the skeletal dysmorphosis, technical limits of the orthodontic appliances or the motivation and compliance needed from the patient. For this reason an orthodontic treatment combined with orthognathic surgery may be indicated.