Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal models of drug-resistant epilepsy.

Objectives: One-third of epileptic patients are resistant to antiepileptic drugs. Few clinical studies with small sample size indicate that polyunsaturated fatty acids could control drug-resistant epilepsy. We examined the efficacy of acute and chronic administration of docosahexaenoic acid (DHA) in two animal models of drug-resistant epilepsies, i.e. 6-Hz psychomotor seizures in mice and lamotrigine (LTG)-resistant kindled rats. Methods: Mice received a single injection of DHA (300 µM, i.c.v.) along with phenytoin (PHT) or LTG (i.p.). Six-Hz electroshock (0.2 milliseconds rectangular pulse width, 3 seconds duration, 44 mA current) was given 15 minutes after DHA, and seizure behaviors were recorded. In LTG-resistant kindled rats, a single dose of DHA (300 µM, i.c.v.) was administered with LTG, and seizure parameters were measured. In chronic treatment, mice received DHA (0.1 g/day, orally) for 30 days. Then, a single dose of LTG or PHT was administered to mice and 6-Hz-induced seizures were recorded. In rats, DHA (1 µM, i.c.v.) was administered during kindling development and effect of LTG in DHA-pretreated LTG-resistant kindled rats was verified. Results: LTG and PHT did not inhibit 6-Hz seizures in mice after single injection of DHA. However, LTG and PHT inhibited 6-Hz seizures in mice that received DHA for 1 month. Acute or chronic administration of DHA to LTG-resistant kindled rats led to the suppression of kindled seizure parameters by LTG. Discussion: DHA removes the 'inherent resistance' of 6-Hz seizures to PHT and LTG, and prevents the development of pharmacodynamic tolerance to LTG in LTG-resistant kindled rats. DHA might have potential to be used as add-on therapy in patients with refractory epilepsy.

Data for zonisamide effect on length and weight of 14 day-old rat pups and abortion rate and day in refractory epileptic pregnant rats.

Length and weight of 14 day-old rat pups and also abortion rate and day on refractory epileptic pregnant rats after treatment with zonisamide (ZNS) are presented. Lamotrigine-resistant chemical kindling procedure was used for inducing of refractory epilepsy. For further interpretation follow the research article: Effect of zonisamide on refractory epilepsy during pregnancy in lamotrigine resistant kindled rats (Sani et al., 2017) [1].

Effect of zonisamide on refractory epilepsy during pregnancy in lamotrigine resistant kindled rats.

Drug-resistant epilepsy with uncontrolled severe seizures despite state-of-the-art medical treatment continues to be a major clinical problem. Pregnancy is a state where drug pharmacokinetic changes are more pronounced and more rapid than any other period of life. The current study investigated the effect of zonisamide (ZNS) on refractory epilepsy during pregnancy in lamotrigine-resistant kindled rats. Fifty-six lamotrigine (LTG)-resistant kindled Wistar rats were divided into five experimental (four pregnant and one non-pregnant) and 2 positive controls (pregnant and non-pregnant) groups and eight intact Wistar rats were put in the negative pregnant control group. Experimental groups received daily ZNS 50mg/kg by oral gavage and 30min later, pentylenetetrazol (PTZ) (30mg/kg) was injected intraperitoneal (i.p) on Gestational Days 10-15 (in rats with or without ZNS or methanol and ethyl acetate as a ZNS solvent challenge in days -5 to 0) or Days 15-20 and for six days in the non-pregnant group. The positive control groups received the ZNS solvent for the same number of days, but the negative pregnant control group did not receive any treatment. Epilepsy was significantly controlled by ZNS in the experimental groups compared to the positive control groups. It was concluded that ZNS can control refractory epilepsy during pregnancy and increase pregnancy survival in refractory epileptic rats.

Prevalence and etiology of subclinical mastitis in dairy ewes in two seasons in Semnan province, Iran.

Twenty-one dairy ewe flocks selected by stratified random sampling were subjected to study the prevalence and etiology of subclinical intramammary infections and to assess the influence of parity on the prevalence of intramammary infections. Also, spontaneous cure rates were determined over study period. A total of 1192 milk samples were collected at 2 weeks after lambing until tenth-week postpartum. All flocks had hand milking; those which were classified by bacterial culture and California Mastitis Test (CMT) as positive were deemed to have glands with subclinical mastitis (SCM). Of 1192 halves examined, 791 samples were collected during spring and 401 samples were collected during summer. Prevalence rate of SCM in spring was 14.7 %; and spontaneous cure that occurred in this season was 88.8 %; coagulase-negative staphylococci (CNS) were the most common isolates (66.6 %). Samples collected in spring showed higher prevalence rate of SCM than summer samples. This rate was 8.9 % in summer. Spontaneous cure rate in this season was 69.4 %, and Staphylococcus aureus (72.2 %) was the most common isolates. SCM was seen at significantly lower rates in left half than in right one (p < 0.05). Multiparous ewes had significantly higher (p < 0.05) SCM prevalence rates than primiparous ewes. The incidence of clinical mastitis (defined as number of clinical cases per 100 ewe-months) was 0.21 and 0.74 in spring and summer, respectively. The isolates from clinical cases in spring were fungi and, from summer, were S. aureus. Also, S. aureus SCM cases were not significantly severe than other SCM cases. In conclusion, multiparous ewes were most at risk, and severity of infection was higher in summer.