Avaliação do efeito do eucaliptol nas convulsões induzidas por pentilenotetrazol em camundongos

The developmental process of epilepsies involves diverse mechanisms that culminate in the hyperactivity of a population of neurons, resulting in a pattern of repeated and rhythmic depolarizations. Antiepileptic drugs act by increasing GABAergic neurotransmission, reducing the effects of glutamate, or blocking ion channels, and are endowed with serious adverse effects that make it difficult for patients to adhere to treatment. This fact has encouraged the search for compounds of natural origin with potential anticonvulsant effect. Thus, the present study aimed to evaluate the effect of eucalyptol in seizures induced by pentylenetetrazole (PTZ). For this, male Swiss mice, orally treated with monotrepene, were used. The first protocol evaluated the toxicity and the estimated LD50 of the compound. Based on the value of LD50, the doses of terpene used in the behavioral and neurochemical tests were selected. For the behavioral tests, groups of mice were pretreated with saline (10 mL/kg, vol), diazepam (2 mg/kg, ip) and eucalyptol (100, 200 and 400 mg/kg, vol) and then with pentylenetetrazole 80 mg/kg, ip) and evaluated for the following parameters: seizure intensity, latency for first seizure and time of death. For neurochemical tests, groups of mice were pretreated with saline (10 mL/kg, v.o.) and eucalyptol (400 mg/kg, i.p.) and subsequently with pentylenetetrazole (80 mg/kg, i.p.); The determination of the concentration of neurotransmitters (monoamines - dopamine, noradrenaline and serotonin) and oxidative stress markers (nitrite and thiobarbituric acid reactive substances - TBARs) were the parameters evaluated. The results were analyzed by ANOVA or Kruskal-Wallis, followed by Student-Newman-Keuls, and Dunns, respectively. Values of p <0.05 were considered significant. The results showed that oral administration of eucalyptol had low toxicity and the estimated LD50 was greater than 2000 mg / kg. In the PTZ-induced seizure test, only the higher dose of monoterpene (400 mg/kg) significantly reduced seizure intensity by 60%, increased latency for onset of the first seizure by 85% and time of death of the animals in 75% in relation to the control. Similarly, treatment with eucalyptol (400 mg/kg) significantly reduced the concentration of noradrenaline, dopamine and serotonin by 50%, 33% and 70%, respectively, in relation to the PTZ-treated group (80 mg/kg). In addition, treatment with eucalyptol (400 mg/kg) significantly reduced the concentration of TBARs by 33%, but not nitrite, relative to the PTZ treated group (80 mg/kg). Taken together, the results show that the monoterpene studied has low oral toxicity and an important anticonvulsant effect, since its administration is capable of attenuating the convulsions chemically induced by pentylenetetrazol with consequent reduction of the concentration of monoamines and the reactive substances of thiobarbituric acid, elements whose increase is associated with the epileptogenesis phenomenon.O processo de desenvolvimento das epilepsias envolve mecanismos diversos que culminam na hiperatividade de uma população de neurônios, resultando em um padrão de despolarizações repetidas e rítmicas. Os fármacos antiepilépticos agem através do aumento da neurotransmissão GABAérgica, da redução dos efeitos do glutamato, ou do bloqueio de canais iônicos, sendo dotados de efeitos adversos sérios que dificultam a adesão do paciente ao tratamento. Este fato tem incentivado a busca por compostos de origem natural com potencial efeito anticonvulsivante. Desta forma, o presente trabalho teve como objetivo avaliar o efeito do eucaliptol nas convulsões induzidas por pentilenotetrazol (PTZ). Para tanto, foram utilizados camundongos Swiss machos, tratados oralmente com o monotrepeno. O primeiro protocolo realizado avaliou a toxicidade e a DL50 estimada do composto. Com base no valor da DL50, foram selecionadas as doses do terpeno utilizadas nos testes comportamentais e neuroqímicos. Para os testes comportamentais, grupos de camundongos foram previamente tratados com salina (10 mL/kg, v.o.), diazepam (2 mg/kg, i.p.) e eucaliptol (100, 200 e 400 mg/kg, v.o.) e posteriormente com pentilenotetrazol (80 mg/kg, i.p.) e avaliados quanto aos seguintes parâmetros: intensidade das convulsões, latência para primeira convulsão e tempo de morte. Para os testes neuroquímicos, grupos de camundongos foram previamente tratados com salina (10 mL/kg, v.o.) e eucaliptol (400 mg/kg, i.p.) e posteriormente com pentilenotetrazol (80 mg/kg, i.p.); a determinação da concentração de neurotransmissores (monoaminas – dopamina, noradrenalina e serotonina) e dos marcadores de estresse oxidativo (nitrito e substâncias reativas do ácido tiobarbitúrico – TBARs) foram os parâmetros avaliados. Os resultados foram analisados por ANOVA ou Kruskal-Wallis, seguido dos testes de Student-Newman-Keuls, e Dunns, respectivamente. Foram considerados significativos os valores de p < 0,05. Os resultados mostraram que a administração oral do eucaliptol apresentou baixa toxicidade e a DL50 estimada foi superior a 2000 mg/kg. No teste das convulsões induzidas por PTZ apenas a dose maior do monoterpeno (400 mg/kg) reduziu de forma significativa a intensidade das convulsões em 60%, aumentou a latência para aparecimento da primeira convulsão em 85% e o tempo de morte dos animais em 75% em relação ao controle. De forma semelhante, o tratamento com eucaliptol (400 mg/kg) reduziu de forma significativa a concentração de noradrenalina, dopamina e serotonina, em 50%, 33% e 70%, respectivamente, em relação ao grupo tratado com PTZ (80 mg/kg). Além disso, o tratamento com eucaliptol (400 mg/kg) reduziu de forma significativa a concentração de TBARs em 33%, mas não de nitrito, em relação ao grupo tratado com PTZ (80 mg/kg). Tomados em conjunto, os resultados mostram que o monoterpeno estudado apresenta baixa toxicidade oral e importante efeito anticonvulsivante, visto que sua administração é capaz de atenuar as convulsões quimicamente induzidas por pentilenotetrazol com consequente redução da concentração de monoaminas e das substâncias reativas do ácido tiobarbitúrico, elementos cujo aumento está associado ao fenômeno da epileptogênese

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies

Ground-state spins and moments of Ga-72,Ga-74,Ga-76,Ga-78 nuclei

Laser spectroscopy was performed on the Ga-72,Ga-74,Ga-76,Ga-78 isotopes at On-Line Isotope Mass Separator (ISOLDE) facility, CERN. Ground-state nuclear spins and moments were extracted from the measured hyperfine spectra. The results are compared to shell-model calculations, which provide a detailed probe of the nuclear wave function. The spin is established from the shape of the hyperfine structure and the parity inferred from a comparison of shell-model calculations with the measured nuclear moments. The ground states of Ga-76,Ga-78 are both assigned a spin and parity of I-pi = 2(-), while Ga-74 is tentatively assigned as I-pi = 3(-). For Ga-72, the results are consistent with the previous I = 3 assignment.status: publishe

Nuclear Spins and Moments of Ga Isotopes Reveal Sudden Structural Changes between N=40 and N=50

Collinear laser spectroscopy was performed on Ga (Z = 31) isotopes at ISOLDE, CERN. A gas-filled linear Paul trap (ISCOOL) was used to extend measurements towards very neutron-rich isotopes (N = 36-50). A ground state (g.s.) spin I = 1/2 is measured for Ga-73, being near degenerate with a 3/2(-) isomer (75 eV less than or similar to E-ex less than or similar to 1 keV). The Ga-79 g.s., with I = 3/2, is dominated by protons in the pi f(5/2) orbital and in Ga-81 the 5/2(-) level becomes the g.s. The data are compared to shell-model calculations in the f(5/2)pg(9/2) model space, calling for further theoretical developments and new experiments.status: publishe