Relationship between oxidative stress and chronic daily headache in children.

The aim of this study was to investigate the relationship between oxidative stress and chronic daily headache (CDH) in children. Although there are reports that oxidative injury may play a role in the pathophysiology of some neurologic disorders, such as migraine and epilepsy, by disrupting or destroying cell membranes through the formation of free radical and reactive oxygen species, the pathophysiology of headache is not clearly established. A total of 38 children (16 boys and 22 girls) with CDH, aged between 7 and 15 years, were enrolled in the study. The control group consisted of 39 healthy children (17 boys and 22 girls), aged between 7 and 14 years. The mean age was 10.9 ± 2.2 years for both the groups. Activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) levels in all the children of both the groups were measured. Mean activities of erythrocyte SOD, CAT, and GPx as well as MDA levels were significantly higher in the study group than in the control group (p < 0.001). The findings of this study suggest that oxidative stress may play a causal or consequential role in children with CDH.

May long term oxcarbazepine treatment be lead to secondary hyperparathyroidism?

BACKGROUND AND PURPOSE: The adverse effects of newer antiepileptic drugs are not well-known. This study assessed the impact of oxcarbazepine (OXC) treatment on bone turnover. METHODS: Forty-four children with idiopathic focal (and/or secondarily generalized) epilepsy who had been treated with OXC for more than 1 year were compared with 33 healthy, age- and sex-matched children. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, osteocalcin, calcitonin, and 25-hydroxyvitamin D, and bone mineral density were measured to evaluate and compare bone mineralization between the two groups. RESULTS: The serum levels of calcium, osteocalcin, 25-hydroxyvitamin D, and bone mineral density did not differ significantly between the study and control groups. However, serum levels of parathyroid hormone, alkaline phosphatase, phosphorus, and calcitonin differed significantly between the two groups. CONCLUSIONS: These findings suggest that OXC treatment leads to secondary hyperparathyroidism with high-turnover bone disease and/or impaired intestinal calcium absorption.

Experimental and theoretical studies of transport through large scale, partially aligned arrays of single-walled carbon nanotubes in thin film type transistors.

Gate-modulated transport through partially aligned films of single-walled carbon nanotubes (SWNTs) in thin film type transistor structures are studied experimentally and theoretically. Measurements are reported on SWNTs grown by chemical vapor deposition with systematically varying degrees of alignment and coverage in transistors with a range of channel lengths and orientations perpendicular and parallel to the direction of alignment. A first principles stick-percolation-based transport model provides a simple, yet quantitative framework to interpret the sometimes counterintuitive transport parameters measured in these devices. The results highlight, for example, the dramatic influence of small degrees of SWNT misalignment on transistor performance and imply that coverage and alignment are correlated phenomena and therefore should be simultaneously optimized. The transport characteristics reflect heterogeneity in the underlying anisotropic metal-semiconductor stick-percolating network and cannot be reproduced by classical transport models.

Effects of neomycin on the development of tolerance to morphine antinociception.

The effects of neomycin on the development of tolerance to morphine antinociception were examined in mice. Because neomycin did not readly cross blood brain barrier, we examined the effects of neomycin following systemic, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections on the morphine tolerance. Daily subcutaneous (s.c.), i.c.v. and i.t. injections of morphine produced tolerance regardless of route of administration. Both i.c.v. and i.t. neomycin, which alone produced no changes in the basal tail flick latencies, significantly attenuated the development of tolerance to antinociception produced by repeated systemic morphine, while intraperitoneal (i.p.) administration of neomycin did not affect morphine tolerance. Further, i.c.v. and i.t. neomycin attenuated the development of tolerance to antinociception produced by repeated i.c.v. and i.t. morphine, respectively, which were not attenuated by systemic neomycin. This results indicate a potential role for neomycin-sensitive Ca2+ channels on the development of tolerance to the morphine antinoception.

Agmatine potentiates the analgesic effect of morphine by an alpha(2)-adrenoceptor-mediated mechanism in mice.

The effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and a combination of agmatine and morphine on tail-flick test have been investigated in mice. Adult male Swiss-Webster mice were used in the study. Agmatine (10, 20 and 40 mg/kg), clonidine (0.15 mg/kg), yohimbine (0.625 and 1.25 mg/kg), or saline were injected into mice intraperitoneally. Morphine (1 and 2 mg/kg) was given subcutaneously. Agmatine alone did not produce any significant change on radiant tail-flick latencies, but it potentiated significantly and dose-dependently morphine-induced (1 mg/kg) analgesia. The potentiating effect of agmatine (40 mg/kg) on morphine-induced analgesia was blocked completely by yohimbine (0.625 mg/kg), a selective alpha(2)-adrenoceptor antagonist, pretreatment. Clonidine (0.15 mg/kg), an alpha(2-)adrenergic receptor agonist, caused a significant increase of the tail-flick latencies of the mice. Yohimbine (0.625 mg/kg) also blocked clonidine-induced analgesia. In addition, yohimbine (0.625 mg/kg) was ineffective on the tail-flick test and did not produce any significant change on the morphine-induced analgesia. Our results indicate that cotreatment of agmatine with morphine produces antinociceptive enhancement via an alpha(2-)adrenergic receptor-mediated mechanism and agmatine-morphine combination may be an effective therapeutic strategy for medical treatment of pain.

Effects of agmatine on ethanol withdrawal syndrome in rats.

Effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, have been investigated on the ethanol withdrawal syndrome in rats. Adult male Wistar rats were used in the study. Ethanol (7.2% v/v) was given to the rats by a liquid diet for 21 days. Agmatine (20, 40, 80 and 160 mg/kg) and saline were injected to rats intraperitoneally 30 min before ethanol withdrawal testing. After 30th min, 2nd and 6th h of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes and tremor were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. Agmatine caused dose-dependent and significant inhibitory effects on stereotyped behaviors, wet dog shakes and tremors during the observation period. It did not cause any significant change in motor coordination of naive (not ethanol-dependent) rats. Our results suggest that agmatine attenuates withdrawal syndrome in ethanol-dependent rats; thus, this drug may be beneficial in the treatment of ethanol dependence.

Effects of Ca2+ channel blockers on apomorphine, bromocriptine and morphine-induced locomotor activity in mice.

The effects of L-type voltage-dependent Ca2+ channel blockers on apomorphine, bromocriptine and morphine-induced changes in locomotor activity were examined in mice. Apomorphine (4 mg/kg) and morphine (20 mg/kg) produced locomotor stimulation. Bromocriptine (8 mg/kg) produced a biphasic effect on motor behaviour, an early depressant phase, followed by locomotor stimulation. Amlodipine (2.5 mg/kg), nicardipine (10 mg/kg), diltiazem (10 mg/kg) and verapamil (10 mg/kg), which by itself did not affect locomotor activity, inhibited the stimulant phase of bromocriptine without altering the depressant phase, while they did not affect apomorphine- and morphine-induced locomotor stimulation. Apomorphine, bromocriptine and morphine-induced locomotor stimulation was decreased by SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol) (0.05 mg/kg) or haloperidol (0.1 mg/kg). These results indicate that L-type voltage-dependent Ca2+ channels are involved in the motor stimulant effect of bromocriptine, but not in apomorphine- and morphine-induced locomotor stimulation. The effects of Ca2+ channel blockers on the dopaminergic system appears not to be directly related to dopamine receptor blockade.

Effects of intrathecally administered aminoglycoside antibiotics, calcium-channel blockers, nickel and calcium on acetic acid-induced writhing test in mice.

1. Antinociceptive effects of intrathecally administered aminoglycoside antibiotics, calcium-channel blockers, nickel and calcium ions on the acetic acid-induced writhing test in mice were examined. 2. Neomycin (0.5-20.0 micrograms/mouse) gentamicin (5-40 micrograms/mouse), nicardipine, diltiazem and verapamil (0.5-80.0 micrograms/mouse) and calcium ions (0.02-1.0 mumol/mouse) exerted a dose-dependent antinociceptive activity on the acetic acid-induced writhing test. Nickel ions (2.5, 5.0 and 10.0 mumol/mouse) were found ineffective in this test. 3. These results suggest that N- and L-type, but not T-type, voltage-dependent calcium channels are implicated in the spinal processing of nociceptive information.

Analgesic effects of amlodipine and its interaction with morphine and ketorolac-induced analgesia.

1. The antinociceptive effects of amlodipine, administered subcutaneously (s.c.), intracerebroventricularly (i.c.v.) and intrathecally (i.t.) were examined with the acetic acid writhing and tail-flick tests in mice. Amlodipine was also tested in combination with morphine and ketorolac. Isobolographic analyses were used to define the nature of functional interactions between amlodipine and morphine or ketorolac. 2. The s.c. (0.1, 1.25, 2.5, 5 and 10 mg/kg), i.c.v. (2.5, 5, 10 and 20 micrograms/mice) and i.t. (2.5, 5, 10 and 20 micrograms/mice) administration of amlodipine exhibited a dose-dependent antinociceptive effect in the writhing test but had no effect on the tail-flick latency. Isobolographic analyses revealed an additive interaction between amlodipine and morphine or ketorolac in the writhing test. 3. These results suggest that amlodipine induces antinociception and increases antinociceptive action of morphine and ketorolac, possibly through a decrease in cellular calcium availability.