ß-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties). β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50) for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated) pathways. β-Citronellol (but not verapamil) inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by receptor-operated Ca2+ channels.

The anticonvulsant effect of geraniol and inclusion complex geraniol: beta-cyclodextrin / El efecto anticonvulsivo de geraniol y la inclusión de geraniol complejo: beta-ciclodextrina

Geraniol (GR) is an acyclic monoterpene alcohol present in essential oils of aromatic plant species used in Brazilian folk medicine for the treatment of epilepsy. The present study was designed to evaluate the anticonvulsant effect of GR and of the inclusion complex geraniol:beta-cyclodextrin (GR:beta-CD). Mice were treated with GR or with GR:beta-CD (50, 100 and 200 mg/kg) 30 min before pentylenetetrazole (PTZ) or strychnine (STN). GR at 200 mg/kg and GR:beta-CD at the doses of 100 and 200 mg/kg significantly increased the latency for the first PTZ-induced convulsion and reduced the percentage of animals that convulsed. The pretreatment of flumazenil did not revert the anticonvulsant effect of GR in the PTZ-induced convulsion model. In the STN-induced convulsion model, the effects of GR were investigated and no difference was found against control. The results demonstrated an anticonvulsant activity of GR in the PTZ-model, which was potentialized by the complexation with beta-CD...

Geraniol (GR) es un alcohol monoterpeno acíclico presentes en los aceites esenciales de las especies de plantas aromáticas utilizadas en la medicina popular brasileña para el tratamiento de la epilepsia. El presente estudio fue diseñado para evaluar el efecto anticonvulsivo del GR y de la inclusión de geraniol complejo: beta-ciclodextrina (GR:beta-CD). Los ratones fueron tratados con GR o con GR:beta- CD (50, 100 y 200 mg/kg) 30 minutos antes de pentylenotetrazole (PTZ) o strichinine (STN). GR a 200 mg/kg y GR:beta-CD en las dosis de 100 y 200 mg/kg aumentó significativamente la latencia para la primera convulsión inducida PTZ-y redujo la porcentaje de animales que convulsionó. El tratamiento previo de flumazenil no revirtió el efecto anticonvulsivo de GR en el modelo de convulsión inducida con PTZ. En el modelo de convulsión inducida com STN, los efectos de GR fueron investigados y no se encontró ninguna diferencia contra el control. Los resultados demostraron una actividad anticonvulsiva de geraniol en el modelo de PTZ, que fue potenciada por la formación de complejos con beta-CD...

Característica clínica e topográfica do glioma maligno em adolescente - Influência do tratamento intranasal com álcool perílico / Clinical and topographic characteristics of primary glioma in youth - Influence the response to perillyl alcohol treatment

Objetivo: Analisar a influência da topografia da lesão tumoral na resposta ao tratamento intranasal com álcool perílico (POH) em jovens com glioma maligno recidivo. Método: Tendo como padrão a faixa etária de 0 a 19 anos, foram incluídos pacientes do sexo masculino (#153; #31) e feminino (#178) com glioma maligno em estágio terminal, recebendo terapia de suporte paliativa e administração intranasal diária de 440 mg de POH. Resultados: Cefaleia intensa, tontura, vômito, crise convulsiva, alteração de comportamento, fraqueza muscular, alteração visual e hemiplegia à direita foram os sintomas prevalentes antes da confirmação diagnóstica de glioma. Análise de imagem mostrou lesão tumoral nas regiões troncocerebral (#153), talamomesencefálica esquerda (#178) e frontotemporal e insular direita (#31). Paciente #178 não respondeu ao tratamento, evoluindo a óbito em três semanas, e paciente #31 permaneceu em tratamento com POH por aproximadamente 54 semanas. Apesar de nova recidiva, paciente #153 apresenta doença estável, sem qualquer evidência clínica de recorrência para mais de 200 semanas em tratamento exclusivo com álcool perílico por via intranasal. Conclusão: Pacientes adolescentes com glioma maligno recidivo apresentaram heterogeneidade de sintomas compatível coma região anatômica comprometida, indicando que a topografia da lesão tumoral foi um fator prognóstico de sobrevida, influenciando inclusive na resposta ao tratamento intranasal com o álcool perílico.

Objective: Analyze the influence of tumor topography on response to intranasal perillyl (POH) treatment in youths with high grade glioma. Method: It was included male patients (#153; #31) with 19 years old and female (#178) with 15 years old with recurrent high grade glioma in terminal stage using supportive therapy and 440 mg POH daily intranasal administration. It was established a relation of clinical data and topographic image with therapeutic response to intranasal POH. Results: Intense headache, dizziness, vomiting, seizures, behavior change, muscle weakness, visual changes and right hemiplegia were the symptoms prevalent before the diagnostic confirmation of glioma. Image analysis showed tumoral lesionin the brain-stem (#153), in the left thalamus-mesencephalic region (#178), and right frontal-temporal and insular regions (#31). Patient #178 did not respond to intranasal POH treatment and rapidly progressed to death within 3 weeks; patient #31 remained in treatment with POH for nearly 54 weeks, and despite new recurrence, patient #153 presents stable disease, without any clinical evidence of recurrence for more than 200 weeks and under treatment exclusively with POH by intranasal route. Conclusion: Childhood patients with high grade malignant glioma had heterogeneity of clinical symptoms compatible with anatomical compromised region indicating that topography of the tumoral lesion was a prognostic factor influencing the overall survival and response to intranasal POH.

Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant’s anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

Correlação da topografia tumoral e edema peritumoral com a resposta terapêutica à administração intranasal do álcool perílico nos gliomas malignos recidivos / Correlation of tumor topography and peritumoral edema with therapeutic response to a new approach for recurrent malignant gliomas, intranasal administration of perillyl alcohol

Objetivo: Avaliar a correlação da topografia tumoral e edema peritumoral com a resposta terapêutica à administração intranasal do álcool perílico (AP) em uma coorte de pacientes com gliomas malignos recidivos. Métodos: Os autores revisaram retrospectivamente 67 pacientes com gliomas malignos recidivos que receberam administração intranasal de 440 mg de AP diariamente. Parâmetros avaliados incluíram aspectos clínicos e os de neuroimagem. Avaliação clínica incluiu dados demográficos, sintomas iniciais e sobrevida global. Dados de imagem incluíram topografia tumoral, volume tumoral, presença de desvio da linha média eextensão de edema peritumoral. Análise bioestatística foi realizada usando testes log rank. Sobrevida global foi medida e analisada pelo método de Kaplan Meier, incluindo intervalos de confiança de 95 por cento. Resultados: Um total de 67 pacientes foi investigado, 52 (77,6 por cento) com glioblastoma (GBM), 10 (14,9 por cento) com astrocitoma anaplásico (AA) e 5 (7,4 por cento) com oligodendrioglioma anaplásico (OA). Todos os cinco pacientes com AO apresentaram tumor de localização lobar. Nos AA, oito casos estavam localizados em região talâmica e dois em região lobar, enquanto que, nos GBM, 11 casos de localização talâmica e 41 lobares. A relação volume tumoral e edema peritumoral foi observada. Pacientes com regressão tumoral e edema peritumoral apresentaram resposta positiva enquanto que aqueles com regressão tumoral sem regressão do edema peritumoral não apresentaram boa evolução clínica. Pacientes com gliomas profundos sobreviveram significativamente mais tempo do que aqueles com gliomas lobares (log rank test, p = 0,0003). Presença de desvio da linha média (> 1 cm) foi estatisticamente significante como fator de risco para a sobrevida mais curta (log rank test,p = 0,0062). Conclusões...

To evaluate the correlation of tumor topography and peritumoral brain edema with the therapeutic response of intranasal administration of perillyl alcohol (POH) in a cohort of patients with recurrent malignant gliomas. Methods: We retrospectively reviewed 67 consecutive patients with recurrent malignant gliomas who received administration intranasal of POH 440 mg daily. The parameters evaluated were clinical features and the neuroimaging findings. Clinical data included demographics, initial symptoms, and overall survival.Imaging analysis included tumor topography, tumor size, presence of midline shift and extent of peritumoraledema. Biostatistics was carried out using log rank tests. Overall survival was measure and analyzedby Kaplan Meier method including 95% confidence intervals. A total of 67 patients were investigated,52 (77.6%) with glioblastoma (GBM), 10 (14.9%) with anaplastic astrocytoma (AA) and 5 (7.4%) withanaplastic oligodendroglioma (AO). All five AO had lobar localization, AA were lobar in 8 cases and deep in 2 cases, whereas GBM were lobar in 41 cases and deep in 11 cases. Results: A relationship between the tumor size and the volume of peritumoral brain edema (PTBE) was observed. Patients with regression of the tumor and PTBE had positive response whereas those with regression of the tumor without PTBE regression had poor prognosis. Patients with deep tumors survived significantly longer than those with lobar gliomas (log rank test, p=0.0003). Presence of midline shift (> 1 cm) was a statistically significant risk factor for shorter survival (log rank test, p=0.0062). Conclusions...

Determination of the maximum inhibitory dilution of cetylpyridinium chloride-based mouthwashes against staphylococcus aureus: an in vitro study

The aim of this in vitro study was to determine the maximum inhibitory dilution (MID) of four cetylpyridinium chloride (CPC)-based mouthwashes: CPC+Propolis, CPC+Malva, CPC+Eucaliptol+Juá+Romã+Propolis (Natural Honey®) and CPC (Cepacol®), against 28 Staphylococcus aureus field strains, using the agar dilution method. Decimal dilutions ranging from 1/10 to 1/655,360 were prepared and added to Mueller Hinton Agar. Strains were inoculated using Steers multipoint inoculator. The inocula were seeded onto the surface of the culture medium in Petri dishes containing different dilutions of the mouthwashes. The dishes were incubated at 37ºC for 24 h. For readings, the MID was considered as the maximum dilution of mouthwash still capable of inhibiting microbial growth. The obtained data showed that CPC+Propolis had antimicrobial activity against 27 strains at 1/320 dilution and against all 28 strains at 1/160 dilution, CPC+Malva inhibited the growth of all 28 strains at 1/320 dilution, CPC+Eucaliptol+Juá+Romã+Propolis inhibited the growth of 2 strains at 1/640 dilution and all 28 strains at 1/320 dilution, and Cepacol® showed antimicrobial activity against 3 strains at 1/320 dilution and against all 28 strains at 1/160 dilution. Data were submitted to Kruskal-Wallis test, showing that the MID of Cepacol® was lower than that determined for the other products (p<0.05). In conclusion, CPC-mouthwashes showed antimicrobial activity against S. aureus and the addition of other substances to CPC improved its antimicrobial effect.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 muL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Clorofórmio e eucaliptol são amplamente utilizados na clínica odontológica como solventes de guta-percha. Entretanto, estes compostos podem representar um perigo à saúde humana, especialmente por causar danos ao aparelho genético e/ou induzir morte celular. Neste estudo, o potencial genotóxico e citotóxico associado à exposição ao clorofórmio e eucaliptol foram avaliados em células de linfoma murino in vitro pelo teste de células individualizadas (teste do cometa) e pelo teste do azul de tripan, respectivamente. Ambos os solventes de guta-percha provaram ser citotóxicos nos mesmos níveis em concentrações de 2,5, 5 e 10 miL/mL (p<0.05). Por outro lado, nenhum dos dois solventes induziu danos ao DNA. Em conclusão, esses resultados sugerem que ambos os compostos testados (clorofórmio e eucaliptol) são potentes citotoxinas, mas não representam um fator que aumenta o nível de danos no DNA em células de mamíferos.