RESUMO
Neisseria gonorrhoeae bacteria are acknowledged as an urgent threat to human health because this species has developed resistances to all of the antibiotics used clinically to treat its infections. N. gonorrhoeae causes the sexually transmitted disease gonorrhoea, but also causes blindness when the bacteria infect the eyes. Infants are particularly susceptible, acquiring the infection from their mothers at birth. We have shown that the monoglyceride monocaprin rapidly kills N. gonorrhoeae and other bacterial species and is non-irritating in ocular assays. Here we show that the physical and chemical properties of monocaprin make it ideal for use in a thickened eye drop formulation to combat eye infections. Monocaprin-containing formulations were assessed using analytical techniques and for antimicrobial activity in vitro and in ex vivo infections. Monocaprin-containing formulations retained activity after three years and are non-irritating, unlike preparations of povidone iodine in our assays. A recommended formulation for further development and investigation is 0.25% monocaprin in 1% HPMC with 1% polysorbate 20.
Assuntos
Antibacterianos/uso terapêutico , Cegueira/tratamento farmacológico , Composição de Medicamentos/métodos , Farmacorresistência Bacteriana/efeitos dos fármacos , Glicerídeos/uso terapêutico , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Soluções Oftálmicas/uso terapêutico , Animais , Antibacterianos/farmacologia , Cegueira/microbiologia , Bovinos , Córnea/efeitos dos fármacos , Córnea/microbiologia , Glicerídeos/farmacologia , Gonorreia/microbiologia , Testes de Sensibilidade Microbiana , Soluções Oftálmicas/farmacologiaRESUMO
Endocannabinoids protect against seizures, but their mechanism of action is still unclear, as they can have effects independent of known cannabinoid receptors. Using Drosophila melanogaster, which lacks canonical cannabinoid receptors, we report that the endocannabinoids anandamide and 2-arachidonoylglycerol protect against seizures in multiple fly seizure models. Surprisingly, inhibition of anandamide catabolism renders flies insensitive to protection by anandamide, indicating that anandamide metabolites are responsible for seizure protection. Consistent with this finding, arachidonic acid, a direct metabolite of anandamide, protects against seizures. To identify downstream effectors, we test for a role of transient receptor potential (TRP) channels and find that the TRPV1 antagonist capsazepine blocks the protective effect of anandamide. Also, a targeted genetic screen of TRP channels identifies water witch as a mediator of protection by anandamide. Using a Drosophila model, we reveal the role of arachidonic acid in seizure protection and identify a cannabinoid-receptor-1/2-independent mechanism of endocannabinoid seizure protection.
Assuntos
Anticonvulsivantes/uso terapêutico , Ácidos Araquidônicos/uso terapêutico , Proteínas de Drosophila/metabolismo , Endocanabinoides/uso terapêutico , Glicerídeos/uso terapêutico , Convulsões/prevenção & controle , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Ácidos Araquidônicos/metabolismo , Cálcio/metabolismo , Modelos Animais de Doenças , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Endocanabinoides/metabolismo , Alcamidas Poli-Insaturadas/metabolismo , Alcamidas Poli-Insaturadas/uso terapêutico , RNA Guia de Cinetoplastídeos/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Convulsões/patologia , Canais de Potencial de Receptor Transitório/genéticaRESUMO
INTRODUCTION: Oral microbiome impacts health and disease. T2DM and periodontitis are associated. Neem (Azadiracta indica) has antibacterial activity against oral microbiota. OBJECTIVES: To characterize oral microbiota (OMB) in saliva samples of T2DM patients by Next generation sequencing. To analyze MCP-1 levels among the T2DM patients before and after a month of neem stick usage as a toothbrush. MATERIALS AND METHODS: Blood and saliva samples were collected from adult T2DM patients before and after the neem stick usage. Metagenomic sequencing was performed on saliva samples targeting V6 region of 16s rRNA. Serum MCP-1 levels were determined using a quantitative sandwich Human MCP-1 standard ABTS development kit (Peprotech, USA). RESULTS: The profile of oral microbiota of T2DM patients (n=24) consists of Streptococcus (95.8%) counts ranging from 2644 to 27,214, Veillonella (72.2%, counts 25-19,709, Neisseria (87.5%) 453-33,445), Rothia (63.6%, 233-6734), Actinomycetes (25%, 161-3730), Fusobacterium (21%, 2252-21,334), and Pigmentiphaga (12.5% 3-16,644). Oral microbiota in healthy controls (n=10), consists of Streptococcus (26.1%), Veillonella (21.9%), Neisseria (16.9%), Haemophilus (10.7%), Actinomycetes (2.6%), Rothia (3.1%), Oribacterium (1.7%). Post neem samples showed drastic reduction in the load of bacteria which was statistically significant. The mean serum MCP-1 before the use of neem stick was 265.18±79.44 (range 141.6-980.5pg/ml) and dropped to 33.6±7.35 after a month of neem stick usage (P value>0.001). CONCLUSION: OMB of T2DM patients and healthy controls were similar, however bacterial loads were significantly higher in T2DM patients. Use of neem stick has a statistically significant reduction on bacterial loads and MCP-1 levels in T2DM patients.
Assuntos
Quimiocina CCL2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Glicerídeos/uso terapêutico , Microbiota/efeitos dos fármacos , Boca/microbiologia , Terpenos/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/metabolismo , Saliva/microbiologiaRESUMO
Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.
Assuntos
Toxidermias/tratamento farmacológico , Glicerídeos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Hypericum , Radiodermite/tratamento farmacológico , Terpenos/uso terapêutico , Adulto , Idoso , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Toxidermias/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia/métodos , Radiodermite/etiologiaRESUMO
OBJECTIVES: The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. METHODS: Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. RESULTS: Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. CONCLUSION: Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement.
Assuntos
Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Glicerídeos/uso terapêutico , Antissépticos Bucais/uso terapêutico , Terpenos/uso terapêutico , Humanos , Resultado do TratamentoRESUMO
To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28% in the AG-PUFA group and 22% in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2% in the AG-PUFA group and 58.5% in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.
Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Hipertrigliceridemia/sangue , Hipertrigliceridemia/dietoterapia , Triglicerídeos/sangue , Idoso , Método Duplo-Cego , Ésteres/química , Ésteres/uso terapêutico , Jejum/sangue , Ácidos Graxos Ômega-3/química , Feminino , Glicerídeos/química , Glicerídeos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. METHODS: A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. RESULTS: The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. CONCLUSIONS: Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.
Assuntos
Quimiorradioterapia/efeitos adversos , Glicerídeos/uso terapêutico , Neoplasias de Cabeça e Pescoço/radioterapia , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Radiodermite/tratamento farmacológico , Terpenos/uso terapêutico , Doença Aguda , Adulto , Idoso , Quimiorradioterapia/métodos , Feminino , Flores/química , Humanos , Hypericum/química , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radioterapia/efeitos adversosRESUMO
BACKGROUND: Shark liver oil (SLO) contains both alkylglycerols (AKG) and squalene and is an ancient remedy among the fishermen on the west coast of Norway and Sweden. Literature reports showed that alkyglycerols enhance Fc-receptor mediated phagocytosis, increase humoral immune response and delay hypersensitivity reactions. METHODS: On this background we performed an open spontaneous study on 40 very old aged surgical patients preoperatively treated with alkyglycerols (500 mg twice a day for 4 weeks), in order to reduce the risks of operation, counteracting the postoperative inflammatory and anergic conditions thus achieving quick and plain recovery. To better understand the possible therapeutic impact of alkyglycerols we compared on a case/control basis treated versus untreated patients submitted contemporarily to the identical operation and exposed to the same environmental and seasonal risks. RESULTS: The onset of complications was reduced in the alkyglycerols treated group and the compliance to the natural treatment was excellent without any serious adverse effect. WBC count and IgG significant increase (respectively p <0.05 and p <0.001) might explain some sort of protection against infectious agents and wound repair adverse events. Also lymphocytes concentration significantly increased in the AKG treated group (p <0.001) whereas a slight decrease was observed in the control group. Conversely neutrophils significantly decreased in the AKG treated group (p <0.001) meaning that patients have no more infections and have re-established their physiologic state. However a significant increase was observed in the control group (p <0.05). CRP significantly decreased in the group receiving AKG (p <0.05), thus evidencing a slight antiinflammtory effect of the product. Also ESR decreased from a baseline in the group receiving AKG. CONCLUSIONS: In conclusion we suggest the opportunity to introduce this nutraceutical product in dosages of 500 mg twice a day to very old people before surgical treatment for an effective modulation of leukocytes and soluble immune reactivity according with the shark liver oil consumption trend in the northern Europe countries folk medicine. For this reason it might be advisable a wider study on a substantially bigger patients cohort focused on the complication rate prevention or control.
Assuntos
Óleos de Peixe/uso terapêutico , Glicerídeos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Idoso de 80 Anos ou mais , Animais , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina M/sangue , Contagem de Leucócitos , Masculino , Tubarões , Procedimentos Cirúrgicos OperatóriosRESUMO
1. The effect of butyric acid glycerides (BAGs) with and without clopidol (CLP) on Eimeria maxima on growth and associated biochemical variables was investigated in broiler chickens. 2. One-day-old chicks were divided into 6 equal groups (Gps) of 30 chicks each; each group was subdivided into 6 equal subgroups. Gp 1 was not infected and not treated. Chicks in Gp 2 were not infected and fed on a ration mixed with 4 g BAGs/kg for 6 successive weeks. Chicks of the other groups were directly inoculated intra-crop with 1 × 10(4) sporulated oocysts of E. maxima at 14 d of age. Gp 3 was infected and not treated. Chicks in the remaining three groups were given diets mixed with the tested drugs for 6 successive weeks. Gp 4 was fed on a diet mixed with CLP (125 g/kg). Gp 5 was given a diet mixed with BAGs (4 g/kg diet). Gp 6 was fed on a diet mixed with both BAGs (4 g/kg diet) and CLP (125 g/kg). 3. Birds in Gps 5 and 6 showed a reduction in the mean oocyst count, lesion scores and developmental stages in the lamina propria and improved growth and biochemical variables. BAG supplementation enhanced growth and production of healthy broilers. 4. It was concluded that BAGs were a useful supplement in broiler diets as an alternative to growth promoters and antimicrobial drugs.
Assuntos
Butiratos/uso terapêutico , Galinhas , Clopidol/uso terapêutico , Coccidiose/veterinária , Coccidiostáticos/uso terapêutico , Eimeria/fisiologia , Doenças das Aves Domésticas/tratamento farmacológico , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Butiratos/administração & dosagem , Galinhas/fisiologia , Clopidol/administração & dosagem , Coccidiose/tratamento farmacológico , Coccidiose/parasitologia , Coccidiostáticos/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Glicerídeos/administração & dosagem , Glicerídeos/uso terapêutico , Masculino , Doenças das Aves Domésticas/parasitologiaRESUMO
BACKGROUND: To evaluate efficacy and cost-effectiveness of a plant-derived wound dressing (ONE), a mixture of hypericum oil (Hypericum perforatum L.) and neem oil (Azadirachta indica A. Juss.), in scalp wounds with exposed bone. PATIENTS AND METHODS: All patients with scalp wounds with exposed bone, following the excision of skin tumors, and treated with ONE in 2011 were included. Time of healing, wound size, area of exposed bone, ease of handling, pain, and complications were evaluated. Costs of dressings and nursing time were compared with those cited in literature for other treatment modalities. RESULTS: Fifteen consecutive patients with a mean age of 76.87 ± 10.3 years (59-90 years) were analyzed. The mean wound size was 10.9 ± 6.84 cm(2) (0.4-22.6 cm(2)) with 4.8 ± 5.9 cm(2) (0.3-20.7 cm(2)) of exposed bone. The time of complete healing by secondary intention was 8.1 (4-20) weeks. Rapid formation of granulation tissue was observed which after 4 weeks covered the entire exposed bone surface in 11 of 15 cases (73%). Dressing change was simple with no pain reported; no infections or other complications occurred. Using ONE for a mean healing time of 56.7 days resulted in mean costs of EUR 423.73, which is substantially lower than those published for fascia lata, negative pressure therapy, or collagen matrix followed by skin grafting (EUR 1,612.82, EUR 4,411.80 and EUR 1,503.72, respectively). CONCLUSION: This retrospective, non-controlled analysis supports ONE as a simple-to-use and safe treatment option for scalp wounds with exposed bone. Treatment costs compare favorably to those published for other treatment modalities.
Assuntos
Bandagens , Glicerídeos/uso terapêutico , Hypericum , Fitoterapia/economia , Fitoterapia/métodos , Extratos Vegetais/economia , Extratos Vegetais/uso terapêutico , Couro Cabeludo/efeitos dos fármacos , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/cirurgia , Terpenos/uso terapêutico , Cicatrização/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SuíçaRESUMO
OBJECTIVE: To observe the efficacy of a plant-derived wound dressing (1 Primary Wound Dressing®), a mixture of hypericum and neem oil, in different types of paediatric burns. METHOD: A retrospective review was conducted over the complete healing course of 9 paediatric patients with a mean age of 8.17±3.35 (1-11 years), presenting mixed, partial or full-thickness burns. The treatment applied by the wound care specialist consisted of daily cleansing of the wound with a saline solution and application of 1 Primary Wound Dressing on the whole wound surface. There was no application of a secondary dressing. The time to heal, wound size, ease of handling, pain and complications were recorded. Procedural and background pain were observed in six of the patients older than 5 years (mean age 9.6±2.39, range 8-11 years). Due to the small number of patients examined during the period studied, it was not possible to perform statistical analyses. RESULTS: The mean wound size was 50.76±48.32cm2 (4.63-132.0cm2). A rapid induction of granulation tissue and re-epithelialisation was observed. Time to complete healing was 16.6±4.69 days (10-22 days). No complications related to wound infection was observed. The 6 patients older than five years reported a strong relief of pain, from an initial value of 7-8 out of 10 to 0 out of 10 within the first week of treatment. This remained at the 0 out of 10 level during the second and third weeks of treatment. CONCLUSION: This retrospective, non-controlled examination suggests that 1 Primary Wound Dressing could be an effective therapy for the treatment of burn wounds, with benefits including pain reduction and simplicity of use. Further evaluations with a larger population are required to document the effectiveness of this plant-derived wound dressing in a controlled fashion. DECLARATION OF INTEREST: There were no external sources of funding for this study. F. Carnevali is a researcher and co-inventor of 1 Primary Wound Dressing®.
Assuntos
Queimaduras/tratamento farmacológico , Glicerídeos/uso terapêutico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Terpenos/uso terapêutico , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico , Azadirachta/química , Bolívia , Queimaduras/complicações , Criança , Pré-Escolar , Feminino , Glicerídeos/análise , Humanos , Hypericum/química , Lactente , Masculino , Curativos Oclusivos , Dor/etiologia , Dor/prevenção & controle , Estudos Retrospectivos , Terpenos/análise , Infecção dos Ferimentos/etiologiaRESUMO
This is the first case reporting the results of using an extract of Hypericum flowers (Hypericum perforatum) and neem oil (Azadirachta indica) in foot wounds with exposed bone in a patient with bilateral advanced diabetic ulcers. The effective use of this cheap treatment in patients with diabetic lesions on the feet, if confirmed in a wide controlled study, might allow the caregivers to take care of patients at home.
Assuntos
Azadirachta , Pé Diabético/tratamento farmacológico , Hypericum , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Idoso , Flores , Glicerídeos/uso terapêutico , Humanos , Masculino , Terpenos/uso terapêutico , Resultado do TratamentoRESUMO
The psychoactive component of the cannabis resin and flowers, delta9-tetrahydrocannabinol (THC), was first isolated in 1964, and at least 70 other structurally related 'phytocannabinoid' compounds have since been identified. The serendipitous identification of a G-protein-coupled cannabinoid receptor at which THC is active in the brain heralded an explosion in cannabinoid research. Elements of the endocannabinoid system (ECS) comprise the cannabinoid receptors, a family of nascent lipid ligands, the 'endocannabinoids' and the machinery for their biosynthesis and metabolism. The function of the ECS is thus defined by modulation of these receptors, in particular, by two of the best-described ligands, 2-arachidonoyl glycerol and anandamide (arachidonylethanolamide). Research on the ECS has recently aroused enormous interest not only for the physiological functions, but also for the promising therapeutic potentials of drugs interfering with the activity of cannabinoid receptors. Many of the former relate to stress-recovery systems and to the maintenance of homeostatic balance. Among other functions, the ECS is involved in neuroprotection, modulation of nociception, regulation of motor activity, neurogenesis, synaptic plasticity and the control of certain phases of memory processing. In addition, the ECS acts to modulate the immune and inflammatory responses and to maintain a positive energy balance. This theme issue aims to provide the reader with an overview of ECS pharmacology, followed by discussions on the pivotal role of this system in the modulation of neurogenesis in the developing and adult organism, memory processes and synaptic plasticity, as well as in pathological pain and brain ageing. The volume will conclude with discussions that address the proposed therapeutic applications of targeting the ECS for the treatment of neurodegeneration, pain and mental illness.
Assuntos
Ácidos Araquidônicos/uso terapêutico , Encéfalo/metabolismo , Endocanabinoides/uso terapêutico , Doenças Neurodegenerativas/patologia , Alcamidas Poli-Insaturadas/uso terapêutico , Ácidos Araquidônicos/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Canabidiol/uso terapêutico , Agonistas de Receptores de Canabinoides/uso terapêutico , Antagonistas de Receptores de Canabinoides/uso terapêutico , Dronabinol/uso terapêutico , Sinapses Elétricas/metabolismo , Endocanabinoides/metabolismo , Glicerídeos/uso terapêutico , Humanos , Inflamação/patologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Neurogênese , Fármacos Neuroprotetores/uso terapêutico , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Alcamidas Poli-Insaturadas/metabolismo , Receptores de Canabinoides/metabolismo , Transmissão SinápticaRESUMO
A 70% ethanol extract of the roots of Livistona chinensis has been investigated, led to the isolation of 13 compounds, including a new ceramide, (2S,3S,4R,9Z)-2-[(2R)-2-hydroxytricosanoylamino]-9-octadecene-1,3,4-triol (2), a new glycosyl ceramide, 1-O-ß-D-glucopyranosyl-(2S,3S,4R,9Z)-2-[(2R)-2-hydroxydocosanoylamino]-9-octadecene-1,3,4-triol (3), three new monoacylglycerols, 1-(34-hydroxytetratriacontanoyl)-sn-glycerol (9), 1-[nonadeca-(9Z,12Z)-dienoyl]-sn-glycerol (10), and 1-[12-hydroxypentatriaconta-(13E,15Z)-dienoyl]-sn-glycerol (11), a new diacylglycerol, 1-(heptadeca-6Z,9Z-dienoyl)-3-(octadeca-6Z,9Z,12Z-trienoyl)-sn-glycerol (12), as well as a new diacylglycerol aminoglycoside, 1-octadecanoyl-2-nonadecanoyl-3-O-(6-amino-6-deoxy)-ß-D-glucopyranosyl-sn-glycerol (13). The structures of new compounds were elucidated, based on spectroscopic, zymologic and chemical methods. Among the compounds tested, compounds 3, 4 and 13 showed significantly antiproliferative effects against the human tumor cell lines (K562, HL-60, HepG2, and CNE-1) with the IC50 of 10-65 µM. To our knowledge, this is first report of the occurrence of ceramides and acylglycerols in the genus Livistona.
Assuntos
Aminoglicosídeos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Arecaceae/química , Ceramidas/uso terapêutico , Glicerídeos/uso terapêutico , Monossacarídeos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Aminoglicosídeos/isolamento & purificação , Aminoglicosídeos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ceramidas/isolamento & purificação , Ceramidas/farmacologia , Glicerídeos/isolamento & purificação , Glicerídeos/farmacologia , Células HL-60 , Células Hep G2 , Humanos , Células K562 , Estrutura Molecular , Monossacarídeos/isolamento & purificação , Monossacarídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/químicaRESUMO
BACKGROUND AND PURPOSE: To evaluate the role of 2-arachidonoyl glycerol (2AG) in the regulation of nausea and vomiting using animal models of vomiting and of nausea-like behaviour (conditioned gaping). EXPERIMENTAL APPROACH: Vomiting was assessed in shrews (Suncus murinus), pretreated with JZL184, a selective monoacylglycerol lipase (MAGL) inhibitor which elevates endogenous 2AG levels, 1 h before administering the emetogenic compound, LiCl. Regulation of nausea-like behaviour in rats by exogenous 2AG or its metabolite arachidonic acid (AA) was assessed, using the conditioned gaping model. The role of cannabinoid CB(1) receptors, CB(2) receptors and cyclooxygenase (COX) inhibition in suppression of vomiting or nausea-like behaviour was assessed. KEY RESULTS: JZL184 dose-dependently suppressed vomiting in shrews, an effect prevented by pretreatment with the CB(1) receptor inverse agonist/antagonist, AM251. In shrew brain tissue, JZL184 inhibited MAGL activity in vivo. In rats, 2AG suppressed LiCl-induced conditioned gaping but this effect was not prevented by AM251 or the CB(2) receptor antagonist, AM630. Instead, the COX inhibitor, indomethacin, prevented suppression of conditioned gaping by 2AG or AA. However, when rats were pretreated with a high dose of JZL184 (40 mg·kg(-1) ), suppression of gaping by 2AG was partially reversed by AM251. Suppression of conditioned gaping was not due to interference with learning because the same dose of 2AG did not modify the strength of conditioned freezing to a shock-paired tone. CONCLUSIONS AND IMPLICATIONS: Our results suggest that manipulations that elevate 2AG may have anti-emetic or anti-nausea potential. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
Assuntos
Ácidos Araquidônicos/uso terapêutico , Benzodioxóis/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Glicerídeos/uso terapêutico , Monoacilglicerol Lipases/antagonistas & inibidores , Náusea/tratamento farmacológico , Piperidinas/uso terapêutico , Vômito/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Endocanabinoides , Medo , Cloreto de Lítio , Masculino , Monoacilglicerol Lipases/metabolismo , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/fisiologia , Musaranhos , Vômito/induzido quimicamenteRESUMO
Mallophages of birds (featherlings) are mostly very tiny and can even as adults better be recognized by their movements than by their elongate body shape when using just the naked eye. Since some species (e.g., the "shaft louse" Menopon gallinae, the elongate feather louse Lipeurus caponis, or Columbicola sp.) may pierce the pulp of feathers or the skin by their biting or scratching mandibles and thus lick the excreted blood, they may be extremely dangerous especially to young birds, even if they only feed by nibbling along the feather surface and/or eat epidermal debris. The present paper reports on the successful treatment of different races of fowls being severely infested with both above cited species. This in vivo treatment was done either by a short dipping of the whole fowl into the 1:33 dilution (with tap water) of a neem seed extract (MiteStop®) or by spraying them with the freshly diluted product. It was seen that the dead mallophages dropped down from the feathers as soon as they were dry again. As a precaution, a second treatment was done by some owners 1 week after the first one in order to eliminate all stages, which eventually might have hatched from untouched nits during the time interval between the two treatments. When controlling the treated fowls 4 weeks after the treatment, in no case (treated once or twice), living motile stages were diagnosed indicating the high efficacy of this nontoxic neem seed extract. When treating in vitro cutoff feathers contaminated with L. caponis, it was seen under the stereomicroscope, that the mallophages tried to run away from the 1:33 water-diluted active compound indicating that there is also a repellent effect. Treated L. caponis stopped leg movements within 3 min and died on their feathers within 1-20 min. Then, the last slight trembling movements of their legs and convulsions of their intestine stopped finally.
Assuntos
Amblíceros/efeitos dos fármacos , Doenças das Aves/tratamento farmacológico , Glicerídeos/uso terapêutico , Inseticidas/uso terapêutico , Iscnóceros/efeitos dos fármacos , Infestações por Piolhos/veterinária , Terpenos/uso terapêutico , Animais , Doenças das Aves/parasitologia , Aves , Seguimentos , Glicerídeos/farmacologia , Inseticidas/farmacologia , Infestações por Piolhos/tratamento farmacológico , Infestações por Piolhos/parasitologia , Terpenos/farmacologia , Resultado do TratamentoRESUMO
We have previously demonstrated that a topical microemulsion can attenuate symptoms and signs of seasonal allergic rhinitis. This likely reflects that the microemulsion interferes with the interaction between the allergen and the mucosa. Whether or not the finding translates to conditions caused by other inhaled agents such as house dust mite allergen is unknown. Patients with perennial allergic rhinitis caused by house dust mite were subjected to topical microemulsion treatment in a randomized, double-blinded and crossover design with isotonic saline as control. Morning symptoms were monitored, change from baseline was assessed and the treatments were compared. On the first days of the isotonic saline and microemulsion runs, before any treatment was given, total nasal symptoms were scored to 2.8 and 3.1 (range 0-9), respectively. Nasal symptoms were reduced by intervention with the microemulsion: the change from baseline was consistent for the microemulsion and the difference between the microemulsion and isotonic saline reached statistical significance in favour of the former. We conclude that intervention with a microemulsion may reduce symptoms of house dust mite allergic rhinitis at natural allergen exposure. Our findings suggest the possibility that topical microemulsions can be a useful option to reduce nasal mucosal exposure to allergen in perennial allergic rhinitis..
Assuntos
Antialérgicos/uso terapêutico , Emulsões/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Administração Intranasal , Adulto , Animais , Estudos Cross-Over , Dermatophagoides pteronyssinus , Método Duplo-Cego , Feminino , Glicerídeos/uso terapêutico , Humanos , Soluções Isotônicas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polissorbatos/uso terapêutico , Propilenoglicol/uso terapêutico , Óleo de Gergelim/uso terapêutico , Cloreto de Sódio/uso terapêutico , Adulto JovemRESUMO
While endocannabinoid modulation of both GABAergic and glutamatergic synaptic transmission and plasticity has been extensively investigated, our understanding of the role of endocannabinoids in protecting neurons from harmful insults remains limited. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous ligand and a full agonist for cannabinoid receptors, exhibits anti-inflammatory and neuroprotective effects via a CB1 receptor (CB1R)-mediated mechanism. However, it is still not clear whether 2-AG is also able to protect neurons from ß-amyloid (Aß)-induced neurodegeneration. Here, we demonstrate that exogenous application of 2-AG significantly protected hippocampal neurons in culture against Aß-induced neurodegeneration and apoptosis. This neuroprotective effect was blocked by SR141716 (SR-1), a selective CB1R antagonist, but not by SR144528 (SR-2), a selective CB2R antagonist, or capsazepine (CAP), a selective transient receptor potential cation channels, subfamily V, member 1 (TRPV1) receptor antagonist. To determine whether endogenous 2-AG is capable of protecting neurons from Aß insults, hippocampal neurons in culture were treated with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), the enzyme hydrolyzing 2-AG. MAGL inhibition that elevates endogenous levels of 2-AG also significantly reduced Aß-induced neurodegeneration and apoptosis. The 2-AG-produced neuroprotective effects appear to be mediated via CB1R-dependent suppression of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) phosphorylation and cyclooxygenase-2 (COX-2) expression. Our results suggest that elevation of endogenous 2-AG by inhibiting its hydrolysis has potential as a novel efficacious therapeutic approach for preventing, ameliorating or treating Alzheimer's disease.
Assuntos
Peptídeos beta-Amiloides/efeitos adversos , Ácidos Araquidônicos/farmacologia , Ácidos Araquidônicos/uso terapêutico , Moduladores de Receptores de Canabinoides/uso terapêutico , Endocanabinoides , Glicerídeos/farmacologia , Glicerídeos/uso terapêutico , Hipocampo/patologia , Degeneração Neural/tratamento farmacológico , Fragmentos de Peptídeos/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Ácidos Araquidônicos/antagonistas & inibidores , Benzodioxóis/farmacologia , Compostos de Bifenilo/farmacologia , Canfanos/farmacologia , Antagonistas de Receptores de Canabinoides , Moduladores de Receptores de Canabinoides/farmacologia , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Técnicas de Cultura de Células , Interações Medicamentosas , Glicerídeos/antagonistas & inibidores , Hipocampo/efeitos dos fármacos , Monoacilglicerol Lipases/antagonistas & inibidores , Degeneração Neural/induzido quimicamente , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Rimonabanto , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the odour-adsorbing properties of biopolymers, with a view to using the findings to develop a novel dressing with odour-adsorbing properties. METHOD: The odour-adsorbing properties of a selection of biopolymers (aloe vera, tea tree oil, neem oil and manuka honey) and three commercially available dressings containing activated charcoal cloth (ACC) were quantitatively assessed using laboratory test equipment. An aloe vera-containing composite dressing, designed and developed by the authors, was also compared with the ACC dressings. RESULTS: Aloe vera was the most adsorbent of the biopolymers and a 40% dilution had comparable values to those of the ACC dressings. Furthermore, values for the novel composite dressing were similar to those of the ACC dressings. CONCLUSION: The novel composite dressing may be a potential alternative to ACC dressings, and has the added advantages of having antimicrobial properties as well as the ability to promote a moist wound environment. However, more research is needed.
Assuntos
Bandagens/normas , Biopolímeros/uso terapêutico , Desodorantes/uso terapêutico , Odorantes , Higiene da Pele/métodos , Ferimentos e Lesões/terapia , Aloe , Anti-Infecciosos Locais/uso terapêutico , Carvão Vegetal/uso terapêutico , Ciclodextrinas/uso terapêutico , Avaliação de Medicamentos , Glicerídeos/uso terapêutico , Mel , Humanos , Necrose , Fitoterapia/métodos , Óleo de Melaleuca/uso terapêutico , Terpenos/uso terapêutico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/patologiaRESUMO
BACKGROUND: Contaminated toothbrushes may play a role in the transmission of local or systemic diseases. As modern dentistry emphasises prevention and infection control, toothbrushes should be correctly stored, disinfected and changed at regular intervals. PURPOSE: The aim of this study was to test the efficacy of 3% neem, 2% triclosan, 0.2% chlorhexidine gluconate and 1% sodium hypochlorite as toothbrush disinfectants against Streptococcus mutans. MATERIALS AND METHODS: This was a double-blind, linear crossover, within-group comparative experimental trial conducted among 40 children aged 12 to 15 years. The study was divided into five phases: (1) distilled water (control); (2) 3% neem; (3) 2% triclosan; (4) 0.2% chlorhexidine gluconate; and (5) 1% sodium hypochlorite. The toothbrushes were collected after 5 days of brushing and were soaked for 12 h in antimicrobial solutions of separate phases, after which the toothbrushes were submitted for microbial analysis to check for the presence of S. mutans. RESULTS: The mean colony-forming units (CFUs) of S. mutans at phase 1 when compared with baseline was not significant (P = 0.17). The other phases had a significant drop in mean CFUs of S. mutans from baseline (P < 0.001). The percentage reduction of mean CFUs of S. mutans from baseline was the highest in phase 2 (86%). CONCLUSION: It can be concluded that all the solutions are effective in toothbrush decontamination, but 3% neem has greater efficacy than other solutions.