Screening of Some Novel 4, 5 Disubstituted 1, 2, 4-Triazole-3-thiones for Anticonvulsant Activity.

OBJECTIVE: In the present study, we synthesized fifteen 4, 5-disubstituted 1, 2, 4-triazol- 3-thione derivatives and evaluated for anticonvulsant activity with neurotoxicity determination. METHODS: The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The molecular docking study was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. The anticonvulsant activity was assessed by maximal electroshock (MES) test and subcutaneous pentylenetetrazol (scPTZ) tests. The neurotoxicity was assessed by rotarod ataxia test. RESULTS: In MES test, compounds 5a, 8a and 9a were found active at 100 mg/kg and five compounds were found active at 300 mg/kg dose after 1 hr of administration. After 4 hr of drug administration, only two compounds 8a and 9a exhibited protection at 100 mg/kg. In scPTZ test, three compounds 2a, 6a and 8a were found active at 100 mg/kg and 7a was active at 300 mg/kg after 1 hr of test drug administration. Most of the compounds were found active in MES test with 8a and 9a being the most active among all. In docking study, 2a was found to be best compound based on the binding energy of -6.5 kcal/mol and estimated inhibition constant of 17.2 µM. CONCLUSION: Majority of synthesized compounds were found active in MES test, whereas only few were found to possess anti scPTZ activity. Among all compounds, only 14a caused motor coordination impairment in rotarod ataxia test at 300 mg/kg 1 hr duration.

Comparison of motor praxis and performance in children with varying levels of developmental coordination disorder.

The praxis test is a less well-documented method to determine functional manifestations of childhood dyspraxia. For this study, children aged 6-8years were recruited as follows: 17 children with DCD, 18 at risk of DCD and 35 without obvious problems in motor coordination. The Movement Assessment Battery for Children (MABC-2) was used to measure motor performance and identify the motor incoordination. This study developed a battery of tests to assess limb praxis using a praxis imagery questionnaire, gesture representation, and questions about knowledge of object use. In the comparison of subtests within the praxis test, significant differences were observed across groups on the praxis imagery questionnaire and gesture representation tests but not on knowledge of object use. Similar results were observed in the correlation analyses, in which a weak relationship between MABC-2 and praxis tests was observed. The DCD group had lower scores on the praxis imagery questionnaire, whereas the group at risk of DCD had lower scores on most gesture production tests. Our study provides a better understanding of the nature of the childhood dyspraxia and sheds light on its effect on motor coordination to identify praxis tests with specific clinical meanings in children with movement disorders.

Biofeedback therapy for dyssynergic defecation.

Dyssynergic defecation is one of the most common forms of functional constipation both in children and adults; it is defined by incomplete evacuation of fecal material from the rectum due to paradoxical contraction or failure to relax pelvic floor muscles when straining to defecate. This is believed to be a behavioral disorder because there are no associated morphological or neurological abnormalities, and consequently biofeedback training has been recommended for treatment. Biofeedback involves the use of pressure measurements or averaged electromyographic activity within the anal canal to teach patients how to relax pelvic floor muscles when straining to defecate. This is often combined with teaching the patient more appropriate techniques for straining (increasing intra-abdominal pressure) and having the patient practice defecating a water filled balloon. In adults, randomized controlled trials show that this form of biofeedback is more effective than laxatives, general muscle relaxation exercises (described as sham biofeedback), and drugs to relax skeletal muscles. Moreover, its effectiveness is specific to patients who have dyssynergic defecation and not slow transit constipation. However, in children, no clear superiority for biofeedback compared to laxatives has been demonstrated. Based on three randomized controlled studies in the last two years, biofeedback appears to be the preferred treatment for dyssynergic defecation in adults.

Visually guided reaching: bilateral posterior parietal lesions cause a switch from fast visuomotor to slow cognitive control.

The visually guided reaching of two patients with bilateral optic ataxia was explored in two experiments. In Experiment 1 simple delayed pointing was compared with immediate pointing. In the immediate pointing task both variable and constant errors increased with target eccentricity. In contrast to the performance of control subjects and contrary to their own beliefs, the patients both showed improved accuracy in the delay condition. This improvement was manifest as a reduction in both pointing variability and in the constant angular error towards the point of fixation. Both angular errors and their improvement with the delay were proportional to target eccentricity. Experiment 2 used a task in which the target was pre-viewed 5s prior to its re-exposure for pointing ('delayed real pointing'). On some trials a conflict was introduced between the present and previous visual information by changing the target's location during the delay. In contrast to control subjects, who ignored the pre-viewed location and aimed directly at the current target, both patients with optic ataxia initiated their movements towards the previously viewed target location. Evidently they relied on off-line information in preference to on-line visual information. In addition, the patients often failed to detect the changes in target location. One of the patients sometimes even guessed incorrectly that the target had changed its location, and her movement trajectory was then more affected by her false belief than by the target's actual location. These findings confirm that posterior parietal lesions severely disrupt direct visuomotor transformations, and suggest that the residual performance is mediated indirectly by expectations or beliefs about target position.

Dose-dependent effects of glutamate in pyridoxine-induced neuropathy.

In order to explore the effects of glutamate in a pyridoxine megadose-induced neuropathy, rats were received glutamate either 0.5 or 1 g/kg/day orally with or without pyridoxine 0.8 g/kg/day intraperitoneally for 14 days. The animal's motor coordination, the muscle power and the thermal threshold were observed daily. The nerve conduction velocity was measured at day 0 and day 15 of the treatment. Glutamate either 0.5 or 1 g/kg/day appeared to have no effect on motor coordination, the nerve conduction velocity and the muscle power score compared with control. However, the thermal response latency was significantly decreased (from day 9) in animals treated with 1 g/kg/day glutamate. In pyridoxine-induced neuropathy rats, glutamate 0.5 g/kg/day significantly decreased the effects of pyridoxine on the sciatic nerve conduction velocity, the muscle power score and the motor coordination. Interestingly, glutamate at a dose of 1 g/kg/day worsened the neurotoxic effects cause by pyridoxine.

Knowing no fear.

People with brain injuries involving the amygdala are often poor at recognizing facial expressions of fear, but the extent to which this impairment compromises other signals of the emotion of fear has not been clearly established. We investigated N.M., a person with bilateral amygdala damage and a left thalamic lesion, who was impaired at recognizing fear from facial expressions. N.M. showed an equivalent deficit affecting fear recognition from body postures and emotional sounds. His deficit of fear recognition was not linked to evidence of any problem in recognizing anger (a common feature in other reports), but for his everyday experience of emotion N.M. reported reduced anger and fear compared with neurologically normal controls. These findings show a specific deficit compromising the recognition of the emotion of fear from a wide range of social signals, and suggest a possible relationship of this type of impairment with alterations of emotional experience.