Cisplatin and ototoxicity in childhood: the perspective of supporting otoprotective agentes.

Cisplatin is an antineoplastic medicine used in the treatment for various types of cancer. Among its side effects is ototoxicity, which may result in a bilateral and irreversible hearing loss. The ototoxic effect in the pediatric population has a bigger impact as it compromises language acquisition. The discovery of drugs with otoprotective effects and the optimal way to administer them have become significant challenges in minimizing the impact of cisplatin regarding auditory function. The objective was to understand otoprotective drugs and their relevance in the preventive treatment to cisplatin-induced ototoxicity in childhood. An integrative review was conducted by consulting databases including PubMed, Bireme, MedLine, LILACS, SciELO, and ClinicalTrials.gov. The search strategy was performed by crossing descriptors (DeCS and MeSH) and free terms. Studies published in English, Spanish, and Portuguese were selected, with no publication year restrictions. Subsequently, articles were selected according to inclusion and exclusion criteria. A total of 736 articles were found in PubMed, 431 in Bireme, 425 in MedLine, 6 in LILACS, 0 in SciELO, and 4 in ClinicalTrials.gov. After document analysis, 12 articles were selected for full analysis. Evidence was found for 8 substances with potential otoprotective effects when used with cisplatin, which tend to minimize the impact of cisplatin regarding auditory function. The substances found were: Amifostine, Dexamethasone, Genistein, Ginkgo Biloba, Lycopene, N-acetylcysteine, Polydatin also Sodium Thiosulfate. In general, these drugs are applied before, during, or after cisplatin infusion, depending on the chosen drug, via intravenous, oral, or transtympanic injections, acting as antioxidant therapy. The biochemical effects of these substances are relevant to their potential otoprotective properties, including the inactivation of oxygen free radicals and electrophilic platinum species. The use of these substances can reduce ototoxicity, decreasing cisplatin-induced hearing loss and improving the confort of life, especially for children.

Dopamine depletion in wistar rats with epilepsy.

The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.

Assessment of serotonergic system in formation of memory and learning / Avaliação do sistema serotonérgico na formação de memória e aprendizagem

Abstract We evaluated the involvement of the serotonergic system on memory formation and learning processes in healthy adults Wistar rats. Fifty-seven rats of 5 groups had one serotonergic nuclei damaged by an electric current. Electrolytic lesion was carried out using a continuous current of 2mA during two seconds by stereotactic surgery. Animals were submitted to learning and memory tests. Rats presented different responses in the memory tests depending on the serotonergic nucleus involved. Both explicit and implicit memory may be affected after lesion although some groups showed significant difference and others did not. A damage in the serotonergic nucleus was able to cause impairment in the memory of Wistar. The formation of implicit and explicit memory is impaired after injury in some serotonergic nuclei.

Resumo Avaliar a participação do sistema serotoninérgico em processos de formação de memória e aprendizagem em ratos Wistar adultos saudáveis. Cinquenta e sete ratos de 5 grupos tinham um núcleo serotoninérgico danificado por uma corrente elétrica. A lesão eletrolítica foi realizada utilizando uma corrente contínua de 2 mA durante dois segundos por cirurgia estereotáxica. Os animais foram submetidos a testes de aprendizagem e memória. Os ratos apresentaram respostas diferentes nos testes de memória, dependendo do núcleo serotoninérgica envolvido. A memória explícita e implícita pode ser afetada após a lesão, embora alguns grupos apresentaram diferença significativa e outros não. A lesão no núcleo serotoninérgico foi capaz de causar danos na memória de Wistar. A formação da memória implícita e explícita é prejudicada após a lesão em alguns núcleos serotoninérgicos.

Assessment of serotonergic system in formation of memory and learning.

We evaluated the involvement of the serotonergic system on memory formation and learning processes in healthy adults Wistar rats. Fifty-seven rats of 5 groups had one serotonergic nuclei damaged by an electric current. Electrolytic lesion was carried out using a continuous current of 2mA during two seconds by stereotactic surgery. Animals were submitted to learning and memory tests. Rats presented different responses in the memory tests depending on the serotonergic nucleus involved. Both explicit and implicit memory may be affected after lesion although some groups showed significant difference and others did not. A damage in the serotonergic nucleus was able to cause impairment in the memory of Wistar. The formation of implicit and explicit memory is impaired after injury in some serotonergic nuclei.

Exercício físico versus programa de exercício pela eletroestimulação com aparelhos de uso doméstico / Physical exercise versus exercise program using electrical stimulation devices for home use

OBJETIVO: Avaliar os efeitos da eletroestimulação por aparelhos de uso doméstico sobre o condicionamento neuromuscular. MÉTODOS: A amostra foi composta por 20 mulheres voluntárias, sedentárias, destras, com idades entre 18 a 25 anos em Maceió, estado de Alagoas, em 2006. As mulheres foram divididas aleatoriamente em dois grupos: as do grupo A foram submetidas a eletroestimulação passiva com aparelhos comerciais e as do grupo B, a exercício físico com resistência. O programa de treinamento dos grupos totalizou 16 sessões em dois meses, com duas sessões semanais. As comparações do peso corporal, da cirtometria, fleximetria, e da força muscular antes e após os exercícios, foram utilizadas utilizando-se o teste T pareado. Nas comparações entre os grupos A e B, foi utilizado o teste t de Student. O nível de significância adotado foi de 5 por cento. RESULTADOS: A comparação da força muscular medida de forma subjetiva antes e após cada um dos procedimentos, mostrou que ocorreu aumento da força em ambos os grupos. Foram observados aumentos significantes na massa e na força muscular apenas nos indivíduos que realizaram exercício voluntário. O exercício físico resistido de flexo-extensão dos joelhos foi efetivo em aumentar massa e força muscular, ao contrário das sessões de eletroestimulação com correntes de freqüência de pulsos de 87 Hz, que não tiveram o mesmo efeito. CONCLUSÕES: Os resultados encontrados mostraram que os aparelhos de eletroestimulação para ganho passivo de condicionamento físico comercializados são menos eficientes do que a prática de exercício físico voluntário.

OBJECTIVE: To evaluate the effects of electrical muscle stimulation with devices for home use on neuromuscular conditioning. METHODS: The study sample comprised 20 sedentary, right-handed, voluntary women aged from 18 to 25 years in the city of Maceió, Northeastern Brazil, in 2006. Subjects were randomly divided into two groups: group A included women who underwent muscle stimulation using commercial electrical devices; group B included those women who performed physical activities with loads. The training program for both groups consisted of two weekly sessions for two months, in a total of 16 sessions. Comparisons of body weight, cirtometry, fleximetry, and muscle strength before and after exercise were determined using the paired t-test. For the comparisons between both groups, Student's t-test was used and a 5 percent significance level was adopted. RESULTS: Muscle strength subjectively assessed before and after each intervention was increased in both groups. Significant increases in muscle mass and strength were seen only in those subjects who performed voluntary physical activity. Resisted knee flexion and extension exercises effectively increased muscle mass and strength when compared to electrical stimulation at 87 Hz which did not produce a similar effect. CONCLUSIONS: The study results showed that electrical stimulation devices for passive physical exercising commercially available are less effective than voluntary physical exercise.

[Physical exercise versus exercise program using electrical stimulation devices for home use]. / Exercício físico versus programa de exercício pela eletroestimulação com aparelhos de uso doméstico.

OBJECTIVE: To evaluate the effects of electrical muscle stimulation with devices for home use on neuromuscular conditioning. METHODS: The study sample comprised 20 sedentary, right-handed, voluntary women aged from 18 to 25 years in the city of Maceió, Northeastern Brazil, in 2006. Subjects were randomly divided into two groups: group A included women who underwent muscle stimulation using commercial electrical devices; group B included those women who performed physical activities with loads. The training program for both groups consisted of two weekly sessions for two months, in a total of 16 sessions. Comparisons of body weight, cirtometry, fleximetry, and muscle strength before and after exercise were determined using the paired t-test. For the comparisons between both groups, Student's t-test was used and a 5% significance level was adopted. RESULTS: Muscle strength subjectively assessed before and after each intervention was increased in both groups. Significant increases in muscle mass and strength were seen only in those subjects who performed voluntary physical activity. Resisted knee flexion and extension exercises effectively increased muscle mass and strength when compared to electrical stimulation at 87 Hz which did not produce a similar effect. CONCLUSIONS: The study results showed that electrical stimulation devices for passive physical exercising commercially available are less effective than voluntary physical exercise.

Behavioral and electroencephalographic analysis of seizures induced by intrahippocampal injection of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera

In this study, the behavioral and electroencephalographic (EEG) analysis of seizures induced by the intrahippocampal injection in rats of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera, was determined. The first alterations occurred during microinjection of granulitoxin (8 µg) into the dorsal hippocampus and consisted of seizure activity that began in the hippocampus and spread rapidly to the occipital cortex. This activity lasted 20-30 s, and during this period the rats presented immobility. During the first 40-50 min after its administration, three to four other similar short EEG seizure periods occurred and the rats presented the following behavioral alterations: akinesia, facial automatisms, head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements. Within 40-50 min, the status epilepticus was established and lasted 8-12 h. These results are similar to those observed in the acute phase of the pilocarpine model of temporal lobe epilepsy and suggest that granulitoxin may be a useful tool not only to study the sodium channels, but also to develop a new experimental model of status epilepticus.

Behavioral and electroencephalographic analysis of seizures induced by intrahippocampal injection of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera.

In this study, the behavioral and electroencephalographic (EEG) analysis of seizures induced by the intrahippocampal injection in rats of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera, was determined. The first alterations occurred during microinjection of granulitoxin (8 microg) into the dorsal hippocampus and consisted of seizure activity that began in the hippocampus and spread rapidly to the occipital cortex. This activity lasted 20-30 s, and during this period the rats presented immobility. During the first 40-50 min after its administration, three to four other similar short EEG seizure periods occurred and the rats presented the following behavioral alterations: akinesia, facial automatisms, head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements. Within 40-50 min, the status epilepticus was established and lasted 8-12 h. These results are similar to those observed in the acute phase of the pilocarpine model of temporal lobe epilepsy and suggest that granulitoxin may be a useful tool not only to study the sodium channels, but also to develop a new experimental model of status epilepticus.

Effect of d-fenfluramine on cortical spreading depression in rats.

We investigated the effect of a single ip injection of d-fenfluramine (d-fen; 5-10 mg/kg), a serotonin reuptake blocker, on cortical spreading depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2% KCl at 20-min intervals. SD propagation was monitored (electrocorticogram and DC-recording) at 2 points on the right parietal surface for 3 h. After a "baseline" recording period (1 h), d-fen was injected and the recording session was continued for 2 h. When compared to the predrug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 +/- 0.63 vs 2.66 +/- 0.51 mm/min; N = 17, P < 0.001), at t = 40 min (3.32 +/- 0.58 vs 2.53 +/- 0.52 mm/min; N = 14, P < 0.001), at t = 60 min (3.68 +/- 0.63 vs 2.92 +/- 0.72 mm/min; N = 11, P < 0.001) and at t = 80 min (3.57 +/- 0.61 vs 3.03 +/- 0.83 mm/min; N = 12, P < 0.05) but not at t = 100 min (3.47 +/- 0.72 vs 3.31 +/- 0.88 mm/min; N = 12) nor at t = 120 min (3.44 +/- 0.67 vs 3.37 +/- 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40%) performed after d-fen in 8 rats (47%), SD velocity could not be evaluated since the phenomenon, after reaching the recording electrode nearest the stimulating point, interrupted the propagation before the second recording electrode was reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of d-fenfluramine on cortical spreading depression in rats

We investigated the effect of a single ip injection of ed-fenfluramine (d-fen; 5-10 mg/kg), a serotinin reuptake blocker, on cortical spreading depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2 percent KCl at 20-min intervals. SD propagation was monitored (electrocorticogram and DC-recording) at 2 points on the right parietal surface for 3 h. After a "baseline" recording period (1 h), d-fen was injected and the recording session was continued for 2 h. When compared to the predrug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 + or - 0.63 vs 2.66 + or - 0.51 mm/min; N = 17, P<0.001), at t = 40 min (3.32 + or - 0.58 vs 2.53 + or - 0.52 mm/min; N = 14, P<0.001), att=60 min (3.68 + or - 0.63 vs 2.92 + or - 0.72 mm/min; N = 11, P<0.001) and at t = 80 min (3.57 + or - 0.61 vs 3.03 + or - 0.83 mm/min; N = 12, P<0.05) but not at t = 100 min (3.47 + or - 0.72 vs 3.31 + or - 0.88 mm/min; N = 12) nor at t = 120 min (3.44 + or - 0.67 vs 3.37 + or - 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40 percent) performed ...