Genotoxic Effects of Prenatal Exposure to Levetiracetam During Pregnancy on Rat Offsprings

WOS: 000348134300013PubMed ID: 25600534Levetiracetam is a new-generation antiepileptic drug initially approved as an adjunctive treatment for patients with refractory partial seizures and is now also used as a monotherapy. The aim of this study was to evaluate the genotoxic effects of levetiracetam exposure during pregnancy on rat offsprings. In this study, we used the newborn pups of rats exposed to levetiracetam during pregnancy. Thirty Sprague-Dawley rats were divided into three groups. The mother rats of groups 1 and 2 were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d) from gestational days 1 to 18 during pregnancy. Group 3 (control group) was not treated with any drug. In vivo sister chromatid exchange (SCE) induction and in vivo micronucleus formation were assessed. Bone marrow from rat pups were used for investigation. As a result of this study, levetiracetam exposure did not alter SCE frequencies or the mean of number of micronuclei in the prenatal period (p>0.05). Levetiracetam did not cause miscarriage during pregnancy in mother rats. The present study highlighted fetal safety after prenatal exposure to levetiracetam.Ondokuz Mayis University BAPOndokuz Mayis University [PYO-TIP-1901.11]We would like to thank Ondokuz Mayis University BAP for supporting our project (PYO-TIP-1901.11)

Quantitative assessment of muscular stiffness in children with cerebral palsy using acoustic radiation force impulse (ARFI) ultrasound elastography

WOS: 000427983200012PubMed: 28900767To evaluate the feasibility of quantitative analysis of muscle stiffness in the medial gastrocnemius muscle (GCM) by acoustic radiation force impulse (ARFI) ultrasound elastography in children with spastic cerebral palsy (CP). Seventeen children with spastic CP and 25 healthy children participated in the study between the years 2016-2017. The medial GCM in the CP group was assessed using the Modified Ashworth Scale (MAS) by a physiatrist. ARFI was used to measure the shear-wave velocities (SWVs) of the medial GCM. The mean SWV value for each MAS score was calculated and used for statistics. The mean SWV values of the medial GCM in the CP and healthy groups were 3.17 +/- 0.81 m/s (mean +/- SD) and 1.45 +/- 0.25 m/s (mean +/- SD), respectively. The SWV of the medial GCM significantly increased in the CP patients when compared with controls (p < 0.001). In addition, the SWV values were correlated with the MAS scores (p < 0.001). The interobserver agreement expressed as the interclass correlation coefficient was 0.65 (95% CI 0.33-0.84, p < 0.001). ARFI imaging demonstrated a difference in muscle stiffness in the medial GCM between the CP and healthy groups. This method is a feasible imaging modality for the noninvasive assessment of contracting muscles in children with CP

Evaluation Of Apoptotic Cell Death Following Transient Maternal Hypotension In Fetal Rat Brain: Temporal Pattern Within The First 24 H After Procedure

Background/aim: To explore the effects of maternal transient systemic hypotension on apoptotic neuronal death in an intrauterine fetal rat brain during the first 24 h after induction of hypotension. Materials and methods: A total of 40 pregnant Sprague-Dawley rats were subjected to either transient systemic hypotension produced for 30 min by blood withdrawal via femoral artery catheterization (hypotension group) or sham operation (control group) on day 15. Two randomly selected fetuses were taken from each rat at 0, 6, 12, and 24 h after the procedure. Apoptosis was evaluated in sections from the whole fetal brain by TUNEL and caspase-3 staining. Results: TUNEL (+) and caspase (+) cells were detected only on the walls of the ventricles of both groups and more abundantly in the hypotension groups than in the control groups at all time points (P < 0.05). The increase in TUNEL (+) and caspase (+) cells was highest at 12 h (P < 0.05) following hypotension compared to the other hypotension groups. Conclusion: Maternal transient systemic hypotension caused the hypoxia-ischemia (HI)-induced death of immature neurons by apoptosis, and this is especially prominent at 12 h after the insult. Determination of the susceptibility of a developing brain to HI at a certain time may have potential significance on the timing of neuroprotective measures.WoSScopu

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.

Contains fulltext : 53630.pdf (publisher's version ) (Closed access)Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-Loken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder

Establishment of interdisciplinary child protection teams in Turkey 2002-2006: Identifying the strongest link can make a difference!

WOS: 000265321200007PubMed ID: 19328549Objectives: The University of Iowa Child Protection Program collaborated with Turkish professionals to develop a training program on child abuse and neglect during 2002-2006 with the goals of increasing professional awareness and number of multidisciplinary teams (MDT), regional collaborations, and assessed cases. This paper summarizes the 5-year outcome. Methods: A team of instructors evaluated needs and held training activities in Turkey annually, and provided consultation when needed. Descriptive analysis was done via Excel and SPSS software. Results: Eighteen training activities were held with 3,570 attendees. Over the study period, the number of MDTs increased from 4 to 14. The MDTs got involved in organizing training activities in their institutions and communities. The number of medical curriculum lectures taught by MDTs to medical students/residents, conferences organized by the MDTs, and lectures to non-medical professional audiences increased significantly (R-2 = 91.4%, 83.8%, and 69.2%, respectively). The number of abuse cases assessed by the MDTs increased by five times compared to pre-training period. Conclusions: A culturally competent training program had a positive impact on professional attitudes and behaviors toward recognition and management of child abuse and neglect in Turkey. The need to partner with policy makers to revise current law in favor of a greater human services orientation became clear. Practice implications: Pioneers in developing countries may benefit from collaborating with culturally competent instructors from countries with more developed child protection systems to develop training programs so that professional development can improve recognition and management of child abuse and neglect. Published by Elsevier Ltd