Therapy for hyperthermia-induced seizures in Scn1a mutant rats

Purpose: Mutations in the SCN1A gene, which encodes the alpha 1 subunit of voltage-gated sodium channels, cause generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). N1417H-Scn1a mutant rats are considered to be an animal model of human FS+ or GEFS+. To assess the pharmacologic validity of this model, we compared the efficacies of eight different antiepileptic drugs (AEDs) for the treatment of hyperthermia-induced seizures using N1417H-Scn1a mutant rats. Methods: AEDs used in this study included valproate, carbamazepine (CBZ), phenobarbital, gabapentin, acetazolamide, diazepam (DZP), topiramate, and potassium bromide (KBr). The effects of these AEDs were evaluated using the hot water model, which is a model of experimental FS. Five-week-old rats were pretreated with each AED and immersed in water at 45 degrees C to induce hyperthermia-induced seizures. The seizure manifestations and video-electroencephalographic recordings were evaluated. Furthermore, the effects of each AED on motor coordination and balance were assessed using the balance-beam test. Key Findings: KBr significantly reduced seizure durations, and its anticonvulsant effects were comparable to those of DZP. On the other hand, CBZ decreased the seizure threshold. In addition, DZP and not KBr showed significant impairment in motor coordination and balance. Significance: DZP and KBr showed potent inhibitory effects against hyperthermia-induced seizures in the Scn1a mutant rats, whereas CBZ exhibited adverse effects. These responses to hyperthermia-induced seizures were similar to those in patients with GEFS+ and SMEI. N1417H-Scn1a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent

Abstract Background Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. Methods We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T2-calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation. Results Significant differences in the SIR and T2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA. Conclusion We evaluated the SIR and T2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI

Insights from an Integrated View of the Biology of Apple Snails (Caenogastropoda: Ampullariidae)

Submitted by sandra infurna ([email protected]) on 2016-02-16T12:59:35Z No. of bitstreams: 1 silvana_thiengo_etal_IOC_2015.pdf: 1030588 bytes, checksum: 1feaf6021ccd94c9bf314dbc7b49ccc8 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-02-16T13:49:31Z (GMT) No. of bitstreams: 1 silvana_thiengo_etal_IOC_2015.pdf: 1030588 bytes, checksum: 1feaf6021ccd94c9bf314dbc7b49ccc8 (MD5)Made available in DSpace on 2016-02-16T13:49:31Z (GMT). No. of bitstreams: 1 silvana_thiengo_etal_IOC_2015.pdf: 1030588 bytes, checksum: 1feaf6021ccd94c9bf314dbc7b49ccc8 (MD5) Previous issue date: 2015Howard University. Department of Biology. Washington, DC, USA / University of Hawaii. Pacific Biosciences Research Center. Honolulu, Hawaii, USA /Smithsonian Institution. National Museum of Natural History. Washington, DC, USA.Southwestern University. Department of Biology. Georgetown, Texas, USA.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina.University of West Florida. Department of Biology. Pensacola, Florida, USA.Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET). La Plata, Argentina.Universidad Nacional del Sur-CONICET. Laboratorio de Ecología, INBIOSUR. Bahia Blanca, Argentina.Hong Kong Baptist University. Department of Biology. Kowloon, Hong Kong.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Malacologia. Rio de Janeiro, RJ, Brasil.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina / Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Área de Biologia. Mendoza, Argentina.NARO Kyushu Okinawa Agricultural Research Center. Kumamoto, Japan.Nara Women’s University. Faculty of Science. Kitauoya-nishi, Nara, Japan.Universidad Nacional del Sur-CONICET. Laboratorio de Ecología, INBIOSUR. Bahia Blanca, Argentina.Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET). La Plata, Argentina.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina / Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Área de Biologia. Mendoza, Argentina.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina / Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Área de Biologia. Mendoza, Argentina.Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET). La Plata, Argentina / Comisión de Investigaciones Científicas (CIC). La Plata, Argentina.Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET). La Plata, Argentina.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina / Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Área de Biologia. Mendoza, Argentina.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina / Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Área de Biologia. Mendoza, Argentina.Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET). La Plata, Argentina.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina / Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Área de Biologia. Mendoza, Argentina.University of Hawaii. Pacific Biosciences Research Center. Honolulu, Hawaii, USA / NARO Kyushu Okinawa Agricultural Research Center. Koshi, Kumamoto, Japan.Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP, CONICET). La Plata, Argentina.Instituto de Fisiología (FCM-UNCuyo). Laboratorio de Fisiología (IHEM-CONICET). Mendoza, Argentina.Universidad Nacional del Sur-CONICET. Laboratorio de Ecología, INBIOSUR. Bahia Blanca, Argentina.Universidad Nacional del Sur-CONICET. Laboratorio de Ecología, INBIOSUR. Bahia Blanca, Argentina.Smithsonian Institution. National Museum of Natural History. Washington, DC, USA..Hong Kong Baptist University. Department of Biology. Kowloon, Hong Kong.Universidad Nacional del Sur-CONICET. Laboratorio de Ecología, INBIOSUR. Bahia Blanca, Argentina.Universidad Nacional del Sur-CONICET. Laboratorio de Ecología, INBIOSUR. Bahia Blanca, Argentina.Florida Institute of Technology. Biological Sciences Department. Melbourne, Florida, USA.The Pomacea Project, Inc., Pensacola, Florida, USA.University of Hawaii. Pacific Biosciences Research Center. Honolulu, Hawaii, USA.Apple snails (Ampullariidae) are among the largest and most ecologically important freshwater snails. The introduction of multiple species has reinvigorated the field and spurred a burgeoning body of research since the early 1990s, particularly regarding two species introduced to Asian wetlands and elsewhere, where they have become serious agricultural pests. This review places these recent advances in the context of previous work, across diverse fields ranging from phylogenetics and biogeography through ecology and developmental biology, and the more applied areas of environmental health and human disease. The review does not deal with the role of ampullariids as pests, nor their control and management, as this has been substantially reviewed elsewhere. Despite this large and diverse body of research, significant gaps in knowledge of these important snails remain, particularly in a comparative framework. The great majority of the work to date concerns a single species, Pomacea canaliculata, which we see as having the potential to become a model organism in a wide range of fields. However, additional comparative data are essential for understanding this diverse and potentially informative group. With the rapid advances in genomic technologies, many questions, seemingly intractable two decades ago, can be addressed, and ampullariids will provide valuable insights to our understanding across diverse fields in integrative biology