Guadalupe Palencia

Chronic Malnutrition Caused By a Corn-Based Diet Lowers the Threshold for Pentylenetetrazol-Induced Seizures in Rats

The incidence of epilepsy is high in developing countries where malnutrition is prevalent. Although malnutrition is not a direct cause of seizures, chronic malnutrition may predispose the brain to seizures. In large undernourished human groups from Latin America, the most common sources of food are corn and corn derivatives. We used a rat model of chornic malnutrition, in which corn tortillas were the only solid food intake, to study the possible influence of malnutrition at late stages of brain development on the dynamics of experimental seizures induced by pentylenetetrazole (PTZ). The threshold and does of PTZ required to produce seizures were greatly reduced in malnourished rats. The model of malnutrition used in the study imitates a form of malnutrition common among large numbers of humans. Our results suggest that chronic malnutrition early in life induces changes that lower the seizure threshold and leave the brain more susceptible to seizures. Whether this observation relates to the high incidence of epilepsy in underdeveloped countries remains to be determined.

In Vitro Effects of Albendazole Sulfoxide and Praziquantel against Taenia solium and Taenia crassiceps Cysts

ABSTRACT We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole sulfoxide (ABZSO) required for their activities against Taenia cysts in vitro as well as the 50 and 99% effective concentrations. The results showed that although the effects of both drugs are time and concentration dependent, ABZSO acts much slower and is less potent than PZQ.

Anti-apoptotic, anti-oxidant, and anti-inflammatory effects of thalidomide on cerebral ischemia/reperfusion injury in rats

Thalidomide has shown protective effects in different models of ischemia/reperfusion damage. To elucidate the mechanisms of such protection, this study assessed the effects of thalidomide on the oxidative stress and inflammatory response induced by ischemia/reperfusion episodes in rats. Rats underwent middle cerebral artery occlusion (MCAO) for 2hours. All animals were sacrificed after different reperfusion times. Rats were administered either DMSO or thalidomide (20mg/kg (i.p.)) at different times before or during reperfusion: 1) 1h before reperfusion; the infarct area was measured 2h after reperfusion. 2) 10min before reperfusion and 80min after reperfusion; the infarct area was measured 24h after reperfusion; and 3) 10min before reperfusion and 1h, 24h, 48h, and 68h after reperfusion; the infarct area was measured 72h after reperfusion. Thalidomide reduced the infarct area 24h and 72h after MCAO, and decreased the neurological deficit in all groups with respect to controls. Thalidomide also lowered significantly the number of TUNEL-positive cells, levels of Bax, caspase-3, lipoperoxidation, and pro-inflammatory cytokines, and increased the levels of SOD1, Bcl-2 and pAkt. These results show that thalidomide has neuroprotective effects, apparently due to its anti-apoptotic, anti-oxidant, and anti-inflammatory effects.

Thalidomide inhibits pentylenetetrazole-induced seizures

Thalidomide was originally synthesized and tested as a sedative, hypnotic and antiemetic; however, after its teratogenicity was noted its use for treatment of neurological and psychiatric disorders was abandoned. We studied the potential anticonvulsant effect of thalidomide: Different doses of thalidomide were tested against seizures induced by 50 mg/kg or 70 mg/kg of pentylenetetrazole (PTZ); the anticonvulsant effect of thalidomide was also compared with that of valproic acid. Seizures and latency time were individually recorded. Thalidomide in low doses (5-10 mg/kg) prevented seizures in all animals treated with 50 mg/kg PTZ; also, in a dose-dependent manner thalidomide inhibited seizures in rats exposed to a high dose of PTZ (70 mg/kg); thalidomide exhibited an anticonvulsant activity similar to that of valproic acid. Thalidomide is an effective anticonvulsant, and further studies on this potential antiepileptic substance seem warranted.

Ultrastructural changes in limb distal nerves of rats with alcoholism and/or malnutrition before and after dietary correction.

To study peripheral nerves changes in chronic alcoholism and in malnutrition, we examined ultrastructurally the distal nerve branches of the digits of rats treated with four different dietary schemes, as follows: controls (n = 22), fed standard rodent diet plus water ad libitum; alcoholism (n = 12), fed the standard diet and 2–12% ethanol in drinking water; malnutrition (n = 21), fed with corn tortillas instead of standard diet; and alcoholism and malnutrition combined (n = 22). After 10 months under these conditions, a proportion of animals from each group were sacrificed. The remaining rats of the malnutrition and alcoholism alone groups were deferred a standard diet. The combined alcohol + malnutrition group was subdivided into standard diet, malnutrition and ethanol. After a further 4 months under these new conditions, the animals were sacrificed. Ultrastructural examination of limb distal nerve branches showed that glycogen‐like particles were more common in malnourished animals, whereas remyelinating axons were more numerous in ethanol‐treated rats. Bands of regeneration were present in both groups, but were more common in animals treated with ethanol. These features decreased significantly when the respective nutritional factor was reversed. The results confirm that ethanol plays a definitive role in the development of alcoholic neuropathy and that malnutrition accentuates, the histopathological abnormalities.

Prolonged Exposure to Lead Lowers the Threshold of Pentylenetetrazole‐induced Seizures in Rats

Summary:  Purpose: The aim of this work was to study the effects of prolonged exposure to lead on the threshold of experimental seizures induced by pentylenetetrazole (PTZ).

Neuroprotective effect of thalidomide on MPTP-induced toxicity.

Thalidomide is a sedative with unique pharmacological properties; studies on epilepsy and brain ischemia have shown intense neuroprotective effects. We analyzed the effect of thalidomide treatment on the neurotoxicity caused by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahidropyridine (MPTP) in mice. Thalidomide was administered at two times; before and after the exposure to MPTP. In both circumstances thalidomide improved the neurotoxicity induced by MPTP as seen by a significant raise of the striatal contents of dopamine and simultaneous decrease of monoamine-oxidase-B (MAO-B). These results indicate that in the experimental model of Parkinsons disease the administration of thalidomide improves the functional damage on the nigrostriatal cell substratum as seen by the production of dopamine. This neuroprotective effect seems to be mediated by inhibition of excitotoxicity. Our results suggest that thalidomide could be investigated as potential adjuvant therapy for Parkinsons disease.

Strong anticonvulsant effect of thalidomide on amygdaloid kindling.

Thalidomide was synthesized more than 50 years ago as hypnotic sedative with unique pharmacologic properties. Recently, we have described a notorious anticonvulsant effect of thalidomide on pentylenetetrazole-induced seizures. Here, we report the results of thalidomide administration on amygdaloid kindling. A total of 100 male Wistar rats were implanted with brain electrodes in the basolateral amygdaloid nucleus and the sensory motor cortex. After surgery the animals received a daily electric stimulus through the amygdaline electrode (500 μA intensity, 60 Hz frequency, 1 ms duration) until seizures appeared. The following treatment groups were made: (a) controls; (b) rats treated daily with thalidomide (10 mg/kg) or with topiramate (80 mg/kg); (c) rats treated with different doses of thalidomide. Significant reduction in the after-discharge and retard of behavioral stages were observed in rats treated with thalidomide or with topiramate as compared with controls (p<0.01): Also, a similar anticonvulsant outcome of thalidomide therapy was obtained with doses of either 2.5, 5, 10 or 50 mg/kg; at 100 mg/kg all epileptic activity was suppressed. Anticonvulsant efficacy of thalidomide was superior in most parameters than that obtained with topiramate. In amygdaloid kindling, which simulates human epilepsy characterized by focal seizures secondarily generalized, low doses of thalidomide display strong anticonvulsant properties.

Thalidomide for treatment of refractory epilepsy.

We have experimentally shown that thalidomide has strong anticonvulsant properties. In an open label study, eight male patients with refractory epilepsy received thalidomide at daily-doses of 200 mg during 1 year, frequency of seizures before and during treatment were compared. The mean number of seizures before thalidomide administration was 26 ± 4 per month; it decreased to 7 ± 1 along thalidomide therapy. Our results indicate that thalidomide has strong therapeutic effects in refractory epilepsy.

Effect of chronic stress on ENU-induced tumors

The relation of stress to cancer is the subject of considerable controversy. We studied the possible influence of chronic stress on the time of development and frequency of tumors induced in rats after a single exposure to ethylnitrosourea during prenatal life. Time of development, localization, incidence, type, and size of tumors were similar in stressed rats and in controls. Our results in this paradigm do not support the hypothesis that chronic stress exerts a potentiating effect on carcinogenesis.