Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures

The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca2+) flux in muscle cells as well as intense locomotor activity. We then screened a library of ∼2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities

The role of capsule endoscopy in the diagnosis of digestive haemorrhage

Gastrointestinal bleeding is a common cause of hospitalization, with a high hospital morbidity and mortality rate, but decreasing compared to previous years due to an important progress in therapeutic endoscopic techniques. It is estimated that 5-7% of gastrointestinal bleedings are of obscure origin, with a normal upper and lower gastrointestinal endoscopy. The capsule endoscopy is the state-of-the-art, non-invasive procedure, providing a fine diagnosis of intestinal lesions, especially those found in the small bowel, difficult to address by other methods. Many studies have been published during the past years regarding the sensibility and outcome of capsule endoscopy in patients with gastrointestinal bleeding, but few underline its definitive role in the diagnosis of digestive bleeding. This review looks at the role of capsule endoscopy in the evaluation of patients with gastrointestinal bleeding from the small bowel and the therapeutic options available

Epilepsy in kcnj10 Morphant Zebrafish Assessed with a Novel Method for Long-Term EEG Recordings.

We aimed to develop and validate a reliable method for stable long-term recordings of EEG activity in zebrafish, which is less prone to artifacts than current invasive techniques. EEG activity was recorded with a blunt electrolyte-filled glass pipette placed on the zebrafish head mimicking surface EEG technology in man. In addition, paralysis of agarose-embedded fish using D-tubocurarine excluded movement artifacts associated with epileptic activity. This non-invasive recording technique allowed recordings for up to one hour and produced less artifacts than impaling the zebrafish optic tectum with a patch pipette. Paralyzed fish survived, and normal heartbeat could be monitored for over 1h. Our technique allowed the demonstration of specific epileptic activity in kcnj10a morphant fish (a model for EAST syndrome) closely resembling epileptic activity induced by pentylenetetrazol. This new method documented that seizures in the zebrafish EAST model were ameliorated by pentobarbitone, but not diazepam, validating its usefulness. In conclusion, non-invasive recordings in paralyzed EAST syndrome zebrafish proved stable, reliable and robust, showing qualitatively similar frequency spectra to those obtained from pentylenetetrazol-treated fish. This technique may prove particularly useful in zebrafish epilepsy models that show infrequent or conditional seizure activity

The analysis of the subjective side of the crime provided by Article 264 of the Republic of Moldova’s Criminal Code

Rezumat. Încadrarea juridică a unei fapte prejudiciabile urmează a fi făcută ţinând cont de cele patru elemente constitutive ale componenţei de infracţiune. Determinarea prezenţei laturii subiective urmează a fi făcută pentru a stabili vinovăţia subiectului faptei prejudiciabile imputate şi a stabili încadrarea juridică corectă. Latura subiectivă ca element constitutiv al componenţei de infracţiune este un factor determinant pentru individualizarea pedepsei penale, or, temei pentru liberarea de răspundere penală în cazul absenţei acesteia. Abstract. Legal framing of a prejudicial act is to be made taking into account the four constituent elements of the criminal offence. The determination of the subjective side’s presence is to be made to establish the guilt of the subject of the imputed prejudicial act and the correct legal classification. The subjective side as a constituent element of the criminal offence component is a determining factor for the individualization of the criminal punishment, a ground for the exemption from criminal liability in case of its absence

Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment

Dravet syndrome is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Na v 1.1 (SCN1A), a voltage-gated sodium cha

Providing for QoS maintenance in wireless IP environments

A flow rejection algorithm for the dynamic RSVP (dRSVP) is proposed. dRSVP is an enhanced version of RSVP, aiming at providing dynamic Quality of Service (QoS) support in a variable bandwidth environment through guarantees of ranges of bandwidth instead of specific values. Flow rejection occurs when the channel quality decreases to a level that even the minimum bandwidth requirements per flow cannot be fulfilled. The proposed algorithm aims at significantly improving the flow dropping probability, without affecting the bandwidth utilization. Its operation is based on setting priority classes and rejecting the minimum required number of flows per class, in order to guarantee QoS to the remaining. Both mathematical analysis and simulation results show that the overall flow rejection probability can be significantly reduced

A flow rejection algorithm for QoS maintenance in a variable bandwidth wireless IP environment

A flow rejection algorithm for the dynamic resource reservation protocol (dRSVP) protocol is proposed. dRSVP is an enhanced version of RSVP, aiming at providing dynamic quality-of-service (QoS) support in a variable bandwidth environment (e.g., wireless) through guarantees of ranges of bandwidth instead of specific values. Flow rejection occurs when the channel quality decreases to a level that even the minimum bandwidth requirements per flow cannot be fulfilled. The proposed algorithm aims at improving the flow dropping probability of dRSVP, without affecting the bandwidth utilization. Its operation is based on setting priority classes and rejecting the minimum required number of flows per class, in order to guarantee QoS to the remaining. Both mathematical analysis and simulation results show that the overall flow dropping probability can be significantly reduced