Ação antimicrobiana de compostos majoritários presentes em óleos essenciais sobre bactérias causadoras de infecções hospitalares

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria

Objective-The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria. Methods and Results-DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (Pf-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-gamma levels, and ameliorated clinical score (day 5) with a trend for increased survival. Conclusion-Therapeutic use of DF in malaria is proposed. (Arterioscler Thromb Vasc Biol. 2012; 32:786-798.)

Plant immunostimulants-Scientific paradigm or myth?

In traditional medicine, numerous plant preparations are used to treat inflammation both topically and systemically. Several anti-inflammatory plant extracts and a few natural product-based monosubstances have even found their way into the clinic. Unfortunately, a number of plant secondary metabolites have been shown to trigger detrimental pro-allergic immune reactions and are therefore considered to be toxic. In the phytotherapy research literature, numerous plants are also claimed to exert immunostimulatory effects. However, while the concepts of plant-derived anti-inflammatory agents and allergens are well established, the widespread notion of immunostimulatory plant natural products and their potential therapeutic use is rather obscure, often with the idea that the product is some sort of "tonic" for the immune system without actually specifying the mechanisms. In this commentary it is argued that the paradigm of oral plant immunostimulants lacks clinical evidence and may therefore be a myth, which has originated primarily from in vitro studies with plant extracts. The fact that no conclusive data on orally administered immunostimulants can be found in the scientific literature inevitably prompts us to challenge this paradigm.

Prophylactic and therapeutic efficacy of nitazoxanide against Cryptosporidium parvum in experimentally challenged neonatal calves

Diarrhoea caused by Cryptosporidium parvum is a major problem in calves younger than 4 weeks of age. To date only a few compounds have been approved for prophylactic and none for therapeutic use. Nitazoxanide (NTZ) has proven its efficacy in vitro against C. parvum and is approved by FDA for the treatment of human cryptosporidiosis. In a first experimental study, 3 uninfected calves were treated with NTZ and pharmacokinetics was followed through blood samples. Serum samples of uninfected treated calves contained both NTZ metabolites (tizoxanide and tizoxanide glucuronide) and oral administration at 12 h intervals was considered as optimal. Three groups of three calves (1-3 days old) were then each inoculated with 1x10(7) oocysts of C. parvum (cattle genotype): the prophylactic group received 15 mg/kg body weight NTZ twice daily orally in milk from 1 day before to 8 days postinoculation (dpi). The therapeutic group received the same dosage of NTZ for 10 days from the appearance of diarrhoea (between 1 and 5 dpi). The control group was left untreated. All calves were monitored daily from day -1 to 28 dpi and faecal samples were collected for evaluation of consistency and for determination of oocyst numbers per gram (OPG) of faeces. Diarrhoea was observed in all calves within the first week. Neither prophylactic nor therapeutic use of NTZ improved the clinical appearance and calves of the therapeutic showed a longer diarrheic episode (p<0.05) with strong altered faecal consistency compared to the untreated control group. The number of days with oocyst excretion did not differ significantly between the groups. In 5 out of 6 infected and treated calves oocyst excretion stopped only after discontinuation of treatment. In the prophylactic and in the control group mean values of the sum of the daily OPG per calf (8.5x10(6) and 8.0x10(6), respectively) and of the mean daily number of OPG (0.3x10(6) and 0.3x10(6), respectively) were similar, while the therapeutic group showed significantly lower values (1.9x10(6) and 0.06x10(6), respectively, p<0.05). However oocyst determinations in this group may have been altered by the severe diarrhoea, diluting oocyst densities in the analysed faecal samples. In conclusion, these preliminary results about the first prophylactic and therapeutic use of NTZ in calves did not show the expected positive effect on the course of the Cryptosporidium-infection, neither on reducing the clinical severity, nor on oocyst excretion.

The feasibility of hybrid solar-biomass power plants in India

We assess the feasibility of hybrid solar-biomass power plants for use in India in various applications including tri-generation, electricity generation and process heat. To cover this breadth of scenarios we analyse, with the help of simulation models, case studies with peak thermal capacities ranging from 2 to 10 MW. Evaluations are made against technical, financial and environmental criteria. Suitable solar multiples, based on the trade-offs among the various criteria, range from 1 to 2.5. Compared to conventional energy sources, levelised energy costs are high - but competitive in comparison to other renewables such as photovoltaic and wind. Long payback periods for hybrid plants mean that they cannot compete directly with biomass-only systems. However, a 1.2-3.2 times increase in feedstock price will result in hybrid systems becoming cost competitive. Furthermore, in comparison to biomass-only, hybrid operation saves up to 29% biomass and land with an 8.3-24.8 $/GJ/a and 1.8-5.2 ¢/kWh increase in cost per exergy loss and levelised energy cost. Hybrid plants will become an increasingly attractive option as the cost of solar thermal falls and feedstock, fossil fuel and land prices continue to rise. In the foreseeable future, solar will continue to rely on subsidies and it is recommended to subsidise preferentially tri-generation plants. © 2012 Elsevier Ltd.

Avaliação dos efeitos tóxicos in vitro e in vivo do extrato hidroetanólico dos frutos de Genipa americana L. (Rubiaceae) em camundongos Swiss

The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).

Avaliação dos efeitos tóxicos in vitro e in vivo do extrato hidroetanólico dos frutos de Genipa americana L. (Rubiaceae) em camundongos Swiss

The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).

The efficacy of Aloe vera, tea tree oil and saliva as first aid treatment for partial thickness burn injuries

Many alternative therapies are used as first aid treatment for burns, despite limited evidence supporting their use. In this study, Aloe vera, saliva and a tea tree oil impregnated dressing (Burnaid) were applied as first aid to a porcine deep dermal contact burn, compared to a control of nothing. After burn creation, the treatments were applied for 20 min and the wounds observed at weekly dressing changes for 6 weeks. Results showed that the alternative treatments did significantly decrease subdermal temperature within the skin during the treatment period. However, they did not decrease the microflora or improve re-epithelialisation, scar strength, scar depth or cosmetic appearance of the scar and cannot be recommended for the first aid treatment of partial thickness burns.

A retrospective cohort study of Acticoat™ versus Silvazine™ in a paediatric population

We wished to determine whether changing our centre's practice of using Acticoat instead of Silvazine as our first-line burns dressing provided a better standard of care in terms of efficacy, cost and ease of use. A retrospective cohort study was performed examining 328 Silvazine treated patients from January 2000 to June 2001 and 241 Acticoat treated patients from July 2002 to July 2003. During those periods the respective dressings were used exclusively. There was no significant difference in age, %BSA and mechanism of burn between the groups. In the Silvazine group, 25.6% of children required grafting compared to 15.4% in the Acticoat group (p=0.001). When patients requiring grafting were excluded, the time taken for re-epithelialisation in the Acticoat group (14.9 days) was significantly less than that for the Silvazine group (18.3 days), p=0.047. There were more wounds requiring long term scar management in the Silvazine group (32.6%) compared to the Acticoat group (29.5%), however this was not significant. There was only one positive blood culture in each group, indicating that both Silvazine and Acticoat are potent antimicrobial agents. The use of Acticoat as our primary burns dressing has dramatically changed our clinical practice. Inpatients are now only 18% of the total admissions, with the vast majority of patients treated on an outpatient basis. In terms of cost, Acticoat was demonstrated to be less expensive over the treatment period than Silvazine . We have concluded that Acticoat is a safe, cost-effective, efficacious dressing that reduces the time for re-epithelialisation and the requirement for grafting and long term scar management, compared to Silvazine.

A review of first aid treatments for burn injuries

Throughout history there have been many different and sometimes bizarre treatments prescribed for burns. Unfortunately many of these treatments still persist today, although they often do not have sufficient evidence to support their use. This paper reviews common first aid and pre-hospital treatments for burns (water--cold or warm, ice, oils, powders and natural plant therapies), possible mechanisms whereby they might work and the literature which supports their use. From the published work to date, the current recommendations for the first aid treatment of burn injuries should be to use cold running tap water (between 2 and 15 degrees C) on the burn, not ice or alternative plant therapies.