Seizures induced by aminooxyacetic acid in mice: pharmacological characteristics

Systemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54-86). AOAA also induced clonic convulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04 mumols (range 0.028-0.06). At the onset of convulsions induced by systemic AOAA (CD97;150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on convulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantoin, and carbamazepine remained ineffective. L-Phenylisopropyladenosine was also found to protect mice against AOAA-induced convulsions, whereas atropine and baclofen had no effect. The seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1 mumols) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2-aminophosphonoheptanoic (AP7), 3-[+/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6-cyano-7-nitro-quinoxaline-2,3-dione and gamma-D-glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid. The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the convulsant action of the drug.     

Age-related anticonvulsant activity of NMDA in the rat caudate-putamen.

Striatal pathways are important for modulating the threshold for seizures in the rat forebrain. N-Methyl-D-aspartate (NMDA), an excitatory amino acid derivative and powerful anticonvulsant agent, when injected into the brain, has been shown to protect adult rats against kindling and pilocarpine-induced seizures when injected into the caudate-putamen. The present study examines whether the anticonvulsant action of NMDA in the caudate-putamen varies with age. Bilateral striatal administration of NMDA was effective in suppressing bicuculline-induced seizures in rats older than 23 days of age. The results suggest that striatal pathways involved in the anticonvulsant activity of NMDA in the caudate-putamen are not functionally active in developing rats before the 4th week of life.     

Cystic spinal dysraphism of the cervical and upper thoracic region

Background Cystic dysraphic lesions of the cervical and upper thoracic region are rare and only a few series have been published about the topic. These malformations can be divided into categories that include both myelocystoceles and the so-called cervical meningoceles or myelomeningoceles.Methods A retrospective study of 18 patients was conducted.Results In 17 patients a squamous or a cicatricial epithelium of variable thickness covered the dome of the lesions, while the base was covered with full-thickness skin. In one case the skin was entirely normal. Four patients displayed associated CNS malformations and three more had systemic congenital anomalies. All patients underwent surgical exploration and the length of time between birth and surgery ranged from 6 h to 9 months. The most frequent surgical finding, seen in 14 patients, was a stalk connecting the dorsal surface of the spinal cord to the cyst. In three patients the findings were consistent with myelocystocele. Only in one case was a true meningocele found. Hydrocephalus and Chiari II malformation were not as consistently associated as in myelomeningoceles. Neurological signs and symptoms were not so marked as in myelomeningoceles and were found in the follow-up of four patients. In two of them there was a non-progressive deficit, probably expressing an imperceptible involvement of the nervous system in the first year of life. The histopathological findings were of three types: neuroglial stalks, fibrovascular stalks and myelocystoceles.Conclusions Cystic dysraphisms of the cervical and upper thoracic region differ clinically and structurally from meningomyelocele and have a more favorable outcome. We believe that these malformations have not been properly labeled and propose a classification based on the structures found inside the cyst.     

Effect of intervention to improve breastfeeding technique on the frequency of exclusive breastfeeding and lactation-related problems.

This randomized clinical trial compared frequencies of exclusive breastfeeding and lactation-related problems during the first 30 days among 74 mothers who received a 30-minute counseling session on breastfeeding technique in the maternity ward, and 137 controls. The frequency of exclusive breastfeeding among mothers who had received intervention was similar to controls by 7 days (79.7% vs 82.5%, respectively) and 30 days (60.8% vs 53.3%). There was no difference between groups in the frequency of sore nipples at 7 and 30 days, in breast engorgement and mastitis, and in the quality of breastfeeding technique at 30 days. Therefore, a single intervention at maternity was not sufficient to improve breastfeeding technique, increase exclusive breastfeeding rates, and reduce the incidence of breastfeeding problems during the first month.     

HCV serotypes in Brazilian patients.

OBJECTIVE: To investigate the prevalence of the different types of hepatitis C virus (HCV) in a population of chronic HCV carriers using the Murex HCV serotyping 1-6 assay. METHODS: All serum samples from these patients had a positive nested PCR HCV reaction. The sera were submitted to ELISA, modified, for the identification of antibodies against HCV serotypes 1, 2, 3, 4, 5 and 6 (Murex HCV serotyping 1-6 assay). RESULTS: The viral serotype was identified in 166 (75.8%) of the 219 patients, 108 (65.11%) males and 58 (34.9%) females. Patient age ranged from 12 to 73 years, with a mean of 41.1 years. The form of acquisition of the disease most frequently reported was blood transfusion. The results showed a predominance of type 1 (70.0%), followed by type 3 (22.3%) and type 2 (4.2%). CONCLUSION: Samples presenting low and very close optical density readings may lead to discrepant diagnoses concerning HCV serotypes and should be confirmed by genotyping. The serotyping can be useful in clinical practice and can be of help in establishing the prognosis of the disease, also favoring epidemiologic studies independently of the technology required for genotyping tests.     

Sudden unexpected death in epilepsy: From the lab to the clinic setting

Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.     

Structural and pharmacological profile of generic enoxaparins used in Brazil

Generic active pharmaceutical ingredients (APIs) have been commonly used in Brazil, since 1999, but most of them are synthetic and small molecules. Recently, a large number of generic enoxaparins were introduced into the market raising concerns related to product-to-product interchangeability, efficiency, and drug counterfeiting. These drugs are produced from biological sources and their production involves complex procedures and purification processes. The present article evaluates several generic enoxaparins, structurally and pharmacologically, and compares them with the branded products. Structural analysis showed that the generic products are, indeed, quite similar to the branded products, however, this similarity cannot be extended to their pharmacological activities. The results showed that generic products must go through extensive structural, pharmacological, and clinical evaluation in order to assess their quality, efficacy and, ultimately, avoid drug counterfeiting before clinical use. Variation was also observed between the branded products, showing that such drugs must be at constant surveillance.