Evaluation of the antioxidant, antibacterial, and antibiofilm activity of the sesquiterpene nerolidol.

The aim of this study was to evaluate the antioxidant, antibacterial, and antibiofilm activities of nerolidol. The antioxidant activity of nerolidol was determined using the total antioxidant activity method. Antibacterial activity was performed using the microdilution method to determine the minimum inhibitory concentration (MIC) against seven standard strains of the ATCC and four bacterial clinical isolates with a resistance profile, following the Clinical and Laboratory Standards Institute (CLSI). The antibiofilm activity of nerolidol was performed using the crystal violet method. The results of the antioxidant test revealed a total antioxidant activity of 93.94%. Nerolidol inhibited the growth of Staphylococcus aureus (MIC = 1 mg/mL), Streptococcus mutans (MIC = 4 mg/mL), Pseudomonas aeruginosa (MIC = 0.5 mg/mL), and Klebsiella pneumoniae (MIC = 0.5 mg/mL). For clinical isolates, nerolidol showed an inhibitory potential against multidrug-resistant P. aeruginosa, K. pneumoniae carbapenemase (MIC = 0.5 mg/mL), methicillin-susceptible S. aureus (MIC = 2 mg/mL), and methicillin-resistant S. aureus (MIC = 2 mg/mL). Nerolidol showed similar antibacterial activity against ATCC strains and hospital clinical isolates with resistance profile, suggesting that even though these strains are resistant to antibiotics, they are still sensitive to nerolidol. Nerolidol exerted a dose-dependent effect on the inhibition of biofilm formation, even at subinhibitory concentrations. Nerolidol inhibited bacterial biofilms of ATCC strains at a rate ranging from 51 to 98%, at concentrations ranging from 0.5 to 4 mg/mL. For clinical bacterial isolates, biofilm inhibition ranged from 6 to 60%. Therefore, the present study showed the antioxidant, antibacterial, and antibiofilm properties of nerolidol.

Effects of Tityus stigmurus (Thorell 1876) (Scorpiones: Buthidae) venom in isolated perfused rat kidneys.

Scorpions belonging to the Tityus genus are of medical interest in Brazil. Among them, Tityus stigmurus is the main scorpion responsible for stings in the Northeast region. After a sting, the scorpion venom distributes rapidly to the organs, reaching the kidneys quickly. However, there are few studies concerning the renal pathophysiology of scorpion poisoning. In this study, we evaluated the effects of T. stigmurus venom (TsV) on renal parameters in isolated rat kidneys. Wistar rats (n = 6), weighing 250-300 g, were perfused with Krebs-Henseleit solution containing 6 g/100 mL bovine serum albumin. TsV at 0.3 and 1.0 µg/mL was tested, and the effects on perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and electrolyte excretion were analyzed. Effects were observed only at TsV concentration of 1.0 µg/mL, which increased PP (controlPP40' = 92.7 ± 1.95; TsVPP40' = 182.0 ± 4.70* mmHg, *p < 0.05), RVR (controlRVR40' = 3.28 ± 0.23 mmHg; TstRVR40' = 6.76 ± 0.45* mmHg, *p < 0.05), UF (controlUF50' = 0.16 ± 0.04; TstUF50' = 0.60 ± 0.10* mL/g/min,*p < 0.05), GFR and electrolyte excretion, with histological changes that indicate renal tubular injury. In conclusion, T. stigmurus venom induces a transient increase in PP with tubular injury, both of which lead to an augmented electrolyte excretion.

Antivenom potential of the latex of Jatropha mutabilis baill. (Euphorbiaceae) against Tityus stigmurus venom: Evaluating its ability to neutralize toxins and local effects in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Species of the Jatropha genus (Euphorbiaceae) are used indiscriminately in traditional medicine to treat accidents involving venomous animals. Jatropha mutabilis Baill., popularly known as "pinhão-de-seda," is found in the semi-arid region of Northeastern Brazil. It is widely used as a vermifuge, depurative, laxative, and antivenom. AIM OF THE STUDY: Obtaining the phytochemical profile of the latex of Jatropha mutabilis (JmLa) and evaluate its acute oral toxicity and inhibitory effects against the venom of the scorpion Tityus stigmurus (TstiV). MATERIALS AND METHODS: The latex of J. mutabilis (JmLa) was obtained through in situ incisions in the stem and characterized using HPLC-ESI-QToF-MS. Acute oral toxicity was investigated in mice. The protein profile of T. stigmurus venom was obtained by electrophoresis. The ability of latex to interact with venom components (TstiV) was assessed using SDS-PAGE, UV-Vis scanning spectrum, and the neutralization of fibrinogenolytic and hyaluronidase activities. Additionally, the latex was evaluated in vivo for its ability to inhibit local edematogenic and nociceptive effects induced by the venom. RESULTS: The phytochemical profile of the latex revealed the presence of 75 compounds, including cyclic peptides, glycosides, phenolic compounds, alkaloids, coumarins, and terpenoids, among others. No signs of acute toxicity were observed at a dose of 2000 mg/kg (p.o.). The latex interacted with the protein profile of TstiV, inhibiting the venom's fibrinogenolytic and hyaluronidase activities by 100%. Additionally, the latex was able to mitigate local envenomation effects, reducing nociception by up to 56.5% and edema by up to 50% compared to the negative control group. CONCLUSIONS: The latex of Jatropha mutabilis exhibits a diverse phytochemical composition, containing numerous classes of metabolites. It does not present acute toxic effects in mice and has the ability to inhibit the enzymatic effects of Tityus stigmurus venom in vitro. Additionally, it reduces nociception and edema in vivo. These findings corroborate popular reports regarding the antivenom activity of this plant and indicate that the latex has potential for treating scorpionism.

Hydrogels based on galactomannan and κ-carrageenan containing immobilized biomolecules for in vivo thermal-burn wound treatment.

Hydrogels based on natural polysaccharides have demonstrated efficacy in epithelial recovery from cutaneous burn wounds. Here, we prepared a double-network hydrogel consisting of galactomannan (from Cassia grandis seeds) and κ-carrageenan (commercially sourced), cross-linked with CaCl2, as a matrix for immobilizing lactoferrin and/or Cramoll, aiming at its applicability as dressings for second-degree burn wounds. The formulations obtained [H - hydrogel, HL - hydrogel + lactoferrin, HC - hydrogel + Cramoll and HLC - hydrogel + lactoferrin + Cramoll] were analyzed rheologically as well as in terms of their stability (pH, color, microbial contamination) for 90 days. The burn was created with an aluminum bar (97 ± 3 °C) in the dorsal region of Wistar rats and subsequently treated with hydrogels (H, HL, HC, HLC) and control saline solution (S). The burn was monitored for 3, 7 and 14 days to evaluate the efficacy of the hydrogels in promoting wound healing. The hydrogels did not reveal significant pH or microbiological changes; there was an increase in brightness and a reduction in opacity for H. The rheological analysis confirmed the gel-like viscoelastic signature of the systems without substantial modification of the basic rheological characteristics, however HLC proved to be more rigid, due to rheological synergy when combining protein biomolecules. Macroscopic analyses confirmed centripetal healing with wound contraction: S < H < HC < HL < HLC. Histopathological analyses showed that hydrogel-treated groups reduced inflammation, tissue necrosis and fibrosis, while promoting re-epithelialization with focal acanthosis, especially in HLC due to a positive synergistic effect, indicating its potential as a promising therapy in the repair of burns.

Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results.

Recurrent glioblastoma (rGBM) remains a major unmet medical need, with a median overall survival of less than 1 year. Here we report the first six patients with rGBM treated in a phase 1 trial of intrathecally delivered bivalent chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Rα2). The study's primary endpoints were safety and determination of the maximum tolerated dose. Secondary endpoints reported in this interim analysis include the frequency of manufacturing failures and objective radiographic response (ORR) according to modified Response Assessment in Neuro-Oncology criteria. All six patients had progressive, multifocal disease at the time of treatment. In both dose level 1 (1 ×107 cells; n = 3) and dose level 2 (2.5 × 107 cells; n = 3), administration of CART-EGFR-IL13Rα2 cells was associated with early-onset neurotoxicity, most consistent with immune effector cell-associated neurotoxicity syndrome (ICANS), and managed with high-dose dexamethasone and anakinra (anti-IL1R). One patient in dose level 2 experienced a dose-limiting toxicity (grade 3 anorexia, generalized muscle weakness and fatigue). Reductions in enhancement and tumor size at early magnetic resonance imaging timepoints were observed in all six patients; however, none met criteria for ORR. In exploratory endpoint analyses, substantial CAR T cell abundance and cytokine release in the cerebrospinal fluid were detected in all six patients. Taken together, these first-in-human data demonstrate the preliminary safety and bioactivity of CART-EGFR-IL13Rα2 cells in rGBM. An encouraging early efficacy signal was also detected and requires confirmation with additional patients and longer follow-up time. ClinicalTrials.gov identifier: NCT05168423 .

A phase I trial of cyclosporine for hospitalized patients with COVID-19.

BACKGROUNDCOVID-19 remains a global health emergency with limited treatment options, lagging vaccine rates, and inadequate healthcare resources in the face of an ongoing calamity. The disease is characterized by immune dysregulation and cytokine storm. Cyclosporine A (CSA) is a calcineurin inhibitor that modulates cytokine production and may have direct antiviral properties against coronaviruses.METHODSTo test whether a short course of CSA was safe in patients with COVID-19, we treated 10 hospitalized, oxygen-requiring, noncritically ill patients with CSA (starting at a dose of 9 mg/kg/d). We evaluated patients for clinical response and adverse events, measured serum cytokines and chemokines associated with COVID-19 hyperinflammation, and conducted gene-expression analyses.RESULTSFive participants experienced adverse events, none of which were serious; transaminitis was most common. No participant required intensive care unit-level care, and all patients were discharged alive. CSA treatment was associated with significant reductions in serum cytokines and chemokines important in COVID-19 hyperinflammation, including CXCL10. Following CSA administration, we also observed a significant reduction in type I IFN gene expression signatures and other transcriptional profiles associated with exacerbated hyperinflammation in the peripheral blood cells of these patients.CONCLUSIONShort courses of CSA appear safe and feasible in patients with COVID-19 who require oxygen and may be a useful adjunct in resource-limited health care settings.TRIAL REGISTRATIONThis trial was registered on ClinicalTrials.gov (Investigational New Drug Application no. 149997; ClinicalTrials.gov NCT04412785).FUNDINGThis study was internally funded by the Center for Cellular Immunotherapies.

Natural Infection with Giardia Is Associated with Altered Community Structure of the Human and Canine Gut Microbiome.

Enteric parasitic infections are among the most prevalent infections in lower- and middle-income countries (LMICs) and have a profound impact on global public health. While the microbiome is increasingly recognized as a key determinant of gut health and human development, the impact of naturally acquired parasite infections on microbial community structure in the gut, and the extent to which parasite-induced changes in the microbiome may contribute to gastrointestinal symptoms, is poorly understood. Enteric parasites are routinely identified in companion animals in the United States, presenting a unique opportunity to leverage this animal model to investigate the impact of naturally acquired parasite infections on the microbiome. Clinical, parasitological, and microbiome profiling of a cohort of 258 dogs revealed a significant correlation between parasite infection and composition of the bacterial community in the gut. Relative to other enteric parasites, Giardia was associated with a more pronounced perturbation of the microbiome. To compare our findings to large-scale epidemiological studies of enteric diseases in humans, a database mining approach was employed to integrate clinical and microbiome data. Substantial and consistent alterations to microbiome structure were observed in Giardia-infected children. Importantly, infection was associated with a reduction in the relative abundance of potential pathobionts, including Gammaproteobacteria, and an increase in Prevotella-a profile often associated with gut health. Taken together, these data show that widespread Giardia infection in young animals and humans is associated with significant remodeling of the gut microbiome and provide a possible explanation for the high prevalence of asymptomatic Giardia infections observed across host species.IMPORTANCE While enteric parasitic infections are among the most important infections in lower- and middle-income countries, their impact on gut microbiota is poorly understood. We reasoned that clinical symptoms associated with these infections may be influenced by alterations of the microbiome that occur during infection. To explore this notion, we took a two-pronged approach. First, we studied a cohort of dogs naturally infected with various enteric parasites and found a strong association between parasite infection and altered gut microbiota composition. Giardia, one of the most prevalent parasite infections globally, had a particularly large impact on the microbiome. Second, we took a database-driven strategy to integrate microbiome data with clinical data from large human field studies and found that Giardia infection is also associated with marked alteration of the gut microbiome of children, suggesting a possible explanation for why Giardia has been reported to be associated with protection from moderate to severe diarrhea.

Tityus stigmurus venom causes genetic damage in blood and testicular cells and affects the number and morphology of gametogenic lineage cells in mice.

Scorpion envenomation represents an important health problem in many parts of the world, due to the high number and severity of accidents. Recent studies demonstrated that some species can produce venoms with genetic damage potential. Here, we evaluated whether Tityus stigmurus venom causes genetic damage in blood and testicular cells of Swiss mice. We also analyzed the effect of the venom on the number of spermatogenic lineage cells. Five groups of mice received 0.387 mg/kg of the venom, intraperitoneally; one group received saline solution (control group). Blood and testicular cells were collected for comet assay and histological analysis at different times after treatment (1, 2, 6, 12, and 48 h). Blood was also collected 48 h after treatment for the micronucleus test in erythrocytes. Histological analysis was performed by counting cells of the spermatogenic lineages; the nuclear area of elongated spermatocytes was also evaluated. Treatment with the venom induced DNA damage that endured from 1 h to 48 h, as confirmed by the comet assay. The micronucleus test demonstrated that the venom induced mutations in erythrocytes. The number of spermatogonia and rounded spermatids decreased in some groups; the number of elongated spermatids increased, and their nuclear size decreased 1 h after treatment. Genetic damage can be caused directly by the venom, but we suggested that reactive oxygen species that result from inflammatory process caused by the envenomation may have an important role in the DNA damage. Genetic damage and apoptosis may explain the changes in the number of spermatogenic cells. Furthermore, the decrease in nuclear area may result from chromatin loss. Genetic damage in testicular cells, associated with alterations in the number and morphology of spermatogenic cells, can result in reproduction disorders in animals, or humans, stung by T. stigmurus.

In Vitro and In Vivo Wound Healing and Anti-Inflammatory Activities of Babassu Oil (Attalea speciosa Mart. Ex Spreng., Arecaceae).

Babassu (Attalea speciosa Mart. ex Spreng., Arecaceae) is a palm tree endemic to Brazil and found mainly in the borders of Amazon forest, where the harvesting of its fruits is an important source of income for more than 300,000 people. Among the communities of coconut breakers women, babassu oil is used in culinary, as fuel, and mostly as medicinal oil for the treatment of skin wounds and inflammation. This study aimed to evaluate in vitro and in vivo the wound healing effects of babassu oil. In vitro, babassu oil increased the migration of L929 fibroblasts, inhibited the production of nitric oxide by LPS-stimulated peritoneal macrophages, and increased the levels of INF-γ and IL-6 cytokines production. In vivo, babassu oil accelerated the healing process in a full-thickness splinted wound model, by an increase in the fibroblasts number, blood vessels, and collagen deposition in the wounds. The babassu oil also increased the recruitment of inflammatory cells into the wound site and showed an anti-inflammatory effect in a chronic ear edema model, reducing ear thickness, epidermal hyperplasia, and myeloperoxidase activity. Thus, these data corroborate the use of babassu oil in folk medicine as a remedy to treat skin wounds.

Evaluation of the cytotoxicity, oral toxicity, genotoxicity, and mutagenicity of the latex extracted from Himatanthus drasticus (Mart.) Plumel (Apocynaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Himatanthus drasticus is a tree popularly known as janaguba. Endemic to Brazil, it is found in the Cerrado and Caatinga biomes, rock fields, and rainforests. Janaguba latex has been used in folk medicine for its antineoplastic, anti-inflammatory, analgesic, and antiallergic activities. However, studies investigating the safety of its use for medicinal purposes are limited. AIM OF THE STUDY: This study aimed to evaluate the toxicity of the latex extracted from H. drasticus. MATERIALS AND METHODS: The latex was extracted from H. drasticus specimens by removing a small area of bark (5 × 30 cm) and then dissolving the exudate in water and lyophilizing it. Phytochemical screening was performed by TLC and GC-MS, protein, and carbohydrate levels. Cell viability was performed by the MTT method. Acute oral toxicity, genotoxicity, and mutagenicity assays were performed in mice. RESULTS: TLC showed the presence of saponins and reducing sugars, as well as steroids and terpenes. The GC-MS analysis of the nonpolar fraction identified lupeol acetate, betulin, and α/ß-amyrin derivatives as the major compounds. The latex was toxic to S-180 cells at 50 and 100 µg/mL. No signals of toxicity or mutagenicity was found in mice treated with 2000 mg/kg of the latex, but genotoxicity was observed in the Comet assay. CONCLUSIONS: H. drasticus latex showed toxicity signals at high doses (2000 mg/kg). Although the latex was not mutagenic to mice, it was genotoxic in the Comet assay in our experimental conditions. Even testing a limit dose of 2000 mg/kg, which is between 10 to 35-fold the amount used in folk medicine, caution must be taken since there is no safe level for genotoxic compounds exposure. Further studies on the toxicological aspects of H. drasticus latex are necessary to elucidate its possible mechanisms of genotoxicity.

Plants and Phytocompounds Active Against Bothrops Venoms.

Snakebite envenomation is an important health problem in tropical countries, with severe human and social consequences. In Latin America, the Bothrops species constitute the main threat to humans, and the envenomation caused by these species quickly develops into severe local tissue damage, including swelling, hemorrhaging, myonecrosis, skin ulceration, and pain. The systemic effects of envenomation are usually neutralized by antivenom serum therapy, despite its intrinsic risks. However, neutralization of local tissue damage remains a challenge. To improve actual therapy, two major alternatives are proposed: the rational design of new specific antibodies for most of the tissue damaging/ poor immunogenic toxins, or the search for new synthetic or natural compounds which are able to inhibit these toxins and complement the serum therapy. Natural compounds isolated from plants, mainly from those used in folk medicine to treat snakebite, are a good choice for finding new lead compounds to improve snakebite treatment and minimize its consequences for the victims. In this article, we reviewed the most promising plants and phytocompounds active against bothropic venoms.

Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids.

BACKGROUND: The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn's disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease. RESULTS: We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens, was associated with diet-induced remission in human pediatric Crohn's disease. CONCLUSIONS: These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn's disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets.

Purification and renal effects of phospholipase A(2) isolated from Bothrops insularis venom.

Bothrops insularis venom contains a variety of substances presumably responsible for several pharmacological effects. We investigated the biochemical and biological effects of phospholipase A(2) protein isolated from B. insularis venom and the chromatographic profile showed 7 main fractions and the main phospholipase A(2) (PLA(2)) enzymatic activity was detected in fractions IV and V. Fraction IV was submitted to a new chromatographic procedure on ion exchange chromatography, which allowed the elution of 5 main fractions designated as IV-1 to IV-5, from which IV-4 constituted the main fraction. The molecular homogeneity of this fraction was characterized by high-performance liquid chromatography (HPLC) and demonstrated by mass spectrometry (MS), which showed a molecular mass of 13984.20 Da; its N-terminal sequence presented a high amino acid identity (up to 95%) with the PLA(2) of Bothrops jararaca and Bothrops asper. Phospholipase A(2) isolated from B. insularis (Bi PLA(2) ) venom (10 microg/mL) was also studied as to its effect on the renal function of isolated perfused kidneys of Wistar rats (n=6). Bi PLA(2) increased perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). Sodium (%TNa(+)) and chloride tubular reabsorption (%TCl(-)) decreased at 120 min, without alteration in potassium transport. In conclusion, PLA(2) isolated from B. insularis venom promoted renal alterations in the isolated perfused rat kidney.

Assessment of the responsiveness of a public health service from the perspective of older adults.

OBJECTIVE: To assess the quality of health care of older adults using as a parameter the assessment of the responsiveness of the service. METHODS: This is a descriptive cross-sectional study conducted in a reference unit of the Brazilian Unified Health System at the outpatient level. The sample was probabilistic and had 385 older adults; data collection occurred in 2014. The domains assessed were: choice, autonomy, confidentiality, dignity, communication, physical facilities, and fast service. To this end, we used Pearson correlation test and Fisher's exact test. RESULTS: The domains of dignity, confidentiality, and communication reached the highest level of adequate responsiveness. On the other hand, freedom of choice and fast service received the worst assessments. Participation in decision-making regarding treatment was significantly lower among the older adults who had no education. In addition, the older adults that self-reported as black receive a lower quality of care regarding clear explanation and respected privacy in the appointment, when compared to users of any other race. CONCLUSIONS: Although most domains studied have receive a positive assessment, we have found a need for an equal care by the health professionals, regardless of race, education level, or any other adjective characteristic of older adults, users of public health services. OBJETIVO: Avaliar a qualidade da atenção à saúde da população idosa usando como parâmetro a avaliação da responsividade do serviço. MÉTODOS: Trata-se de um estudo descritivo, de corte transversal, realizado em uma unidade de referência do Sistema Único de Saúde em nível ambulatorial. A amostra foi probabilística composta por 385 idosos e a coleta de dados ocorreu em 2014. Foram avaliados os domínios: escolha, autonomia, confidencialidade, dignidade, comunicação, instalações físicas e atendimento rápido. Para tanto, foram utilizados o teste de correlação de Pearson e o teste de Fisher. RESULTADOS: Os domínios dignidade, confidencialidade e comunicação atingiram o maior nível de responsividade adequada. Por outro lado, a liberdade de escolha e o atendimento rápido receberam as piores avaliações. A participação na tomada de decisões a respeito do tratamento foi significativamente menor entre os idosos que não frequentaram a escola. Além disso, os idosos que se autodeclararam negros receberam um atendimento de menor qualidade no que diz respeito à explicação clara e a privacidade respeitada mediante consulta, quando comparados aos usuários de outra raça. CONCLUSÕES: Apesar de a maioria dos domínios estudados receberem uma avaliação positiva, evidenciou-se a necessidade de um atendimento igualitário por parte dos profissionais de saúde, independentemente de raça, nível de escolaridade ou qualquer outra característica adjetiva referente aos usuários idosos atendidos nos serviços de saúde públicos.

Renal effects of Bunodosoma caissarum crude extract: Prostaglandin and endothelin involvement.

Sea anemones contain a variety of interesting biologically active compounds, including some potent toxins. PLA2 from Bunodosoma caissarum, a sea anemone endemic in the Brazilian southern coast, has shown renal alterations on isolated kidney. The aim of this study was to evaluate the renal and vascular effects of B. caissarum crude extract (BcE) on isolated perfused kidney and arteriolar mesenteric bed, as well the involvement of prostaglandins and endothelin. BcE did not show any effect on arteriolar mesenteric bed, but increased perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and decreased the percentage of sodium tubular transport on isolated perfused kidney. Indomethacin blocked the renal effects induced by BcE and tezosentan only partially blocked these effects. These results demonstrate the effects of BcE on kidney in situ, suggesting the involvement of prostaglandins and endothelin.

Renal effects and vascular reactivity induced by Tityus serrulatus venom.

Tityus serrulatus, popularly known as yellow scorpion, is one of the most studied scorpion species in South America and its venom has supplied some highly active molecules. The effects of T. serrulatus venom upon the renal physiology in human showed increased renal parameters, urea and creatinine. However, in perfused rat kidney the effects were not tested until now. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution containing 6% (g weight) of previously dialysed bovine serum albumin. The effects of T. serrulatus venom were studied on the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), sodium tubular transport (%TNa+), potassium tubular transport (%TK+) and chloride tubular transport (%TCl-). Tityus serrulatus venom (TsV; 10 microg/mL) was added to the system 30 min after the beginning of each experiment (n=6). This 30 min period was used as an internal control. The mesenteric bed was perfused with Krebs solution kept warm at 37 degrees C by a constant flow (4 mL/min), while the variable perfusion pressure was measured by means of a pressure transducer. The direct vascular effects of TsV (10 microg/mL/min; n=6), infused at a constant rate (0.1 mL/min), were examined and compared to the infusion of the vehicle alone at the same rate. TsV increased PP (PP30'=127.8+/-0.69 vs PP60'=154.2+/-14 mmHg*, *p<0.05) and RVR (RVR30'=6.29+/-0.25 vs RVR60'=8.03+/-0.82 mmHg/mLg(-1)min(-1)*, *p<0.05), decreased GFR (GFR30'=0.58+/-0.02 vs GFR60'=0.46+/-0.01mLg(-1)min(-1)*, *p<0.05) and UF (UF30'=0.135+/-0.001 vs UF60'=0.114+/-0.003mLg(-1)min(-1)*, *p<0.05). Tubular transport was not affected during the whole experimental period (120 min). On the other hand, the infusion of TsV (10 microg/mL/min) increased the basal perfusion pressure of isolated arteriolar mesenteric bed (basal pressure: 74.17+/-3.42 vs TsV 151.8+/-17.82 mmHg*, *p<0.05). TsV affects renal haemodynamics probably by a direct vasoconstrictor action leading to decreased renal flow.

Antinociceptive Effect of the Essential Oil Obtained from the Leaves of Croton cordiifolius Baill. (Euphorbiaceae) in Mice.

Croton cordiifolius Baill. is a shrub known as "quebra-faca" and is used to treat inflammation, pain, wounds, and gastrointestinal disturbances in the semiarid region in the northeast of Brazil. In an ethnobotanical survey in the state of Pernambuco, "quebra-faca" use was cited in 33% of the interviews. Thus, we decided to evaluate the antinociceptive effects of the essential oil from C. cordiifolius (CcEO). Chemical analysis by gas chromatography-mass spectrometry revealed 1,8-cineole (25.09%) and α-phellandrene (15.43%) as major constituents. Antinociceptive activity was evaluated using murine models of chemically induced pain (writhing induced by acetic acid, formalin, capsaicin, and glutamate tests). Opioid and central nervous systems (CNS) involvement were also investigated. Regarding antinociceptive activity, CcEO (50 and 100 mg/kg) reduced the number of writhing responses induced by acetic acid and decreased the licking times in both phases of the formalin test. CcEO also was evaluated in capsaicin- and glutamate-induced nociception. While no effect was observed in the capsaicin test, CcEO (100 mg/kg) was effective in the glutamate test. Naloxone, an opioid antagonist, did not affect the antinociceptive activity of CcEO in writhing test. In conclusion, the antinociceptive effect of CcEO could be explained, at least in part, by inhibition of the glutamatergic system.

Conhecimento e práticas de usuários com diabetes mellitus sobre a automonitorização da glicemia capilar no domicilio / Knowledge and practices of users with diabetes mellitus on capillary blood glucose self-monitoring at home / Conocimientos y prácticas de los usuarios con diabetes mellitus en sangre capilar glucosa autocontrol en casa

Objective:To analyze the knowledge and practices of users with Diabetes Mellitus (DM) on the capillary blood glucose self-monitoring (AMGC) held at home. Methods: descriptive-exploratory study with qualitative methodology, developed in April and May 2013, with users with DM in the public health system of an interior. The data were collected through interviews and categorial analysis verified the sample. The theme was selected by saturation of the speech totaling 12 DM users that perform AMGC at home. Results: the content analysis of data made it possible to identify three categories: realization of non-rational AMGC; The absence of educational programmes to steer on the realization of AMGC; Insufficient availability of inputs to users who perform AMGC. Conclusion: Despite advances legally reached by public policies, users with DM are unaware of the legislation and how it directly interferes in the conduct of AMGC's

Objetivo: Analisar o conhecimento e as práticas de usuários com Diabetes Mellitus (DM) acerca da Automonitorização da Glicemia Capilar (AMGC) realizada no domicílio. Métodos: Estudo descritivo-exploratório, com metodologia qualitativa, desenvolvido em abril e maio 2013, com usuários com DM atendidos pelo sistema público de saúde de um interior pernambucano. Os dados foram coletados por meio de entrevistas e verificados por análise categorial temática, a amostra foi selecionada por meio da saturação do discurso totalizando 12 usuários com DM que realizam a AMGC no domicílio. Resultados: A análise de conteúdo dos dados possibilitou identificar três categorias: Realização da AMGC de forma não racional; Ausência de programas educativos para orientar sobre a realização da AMGC; Disponibilização insuficiente de insumos aos usuários que realizam a AMGC. Conclusão: Apesar dos avanços legalmente alcançados pelas políticas públicas, os usuários com DM desconhecem a legislação e como está interfere diretamente na realização da AMGC

Objetivo: Analizar los conocimientos y prácticas de los usuarios con Diabetes Mellitus (DM) de la glucosa en sangre capilar Self-monitoring (AMGC) llevó a cabo en casa. Métodos: estudio descriptivo exploratorio con metodología cualitativa, desarrollado en abril y mayo de 2013, con usuarios con DM en el sistema de salud pública de un interior. Los datos fueron recogidos a través de entrevistas y análisis categorial verificado que el tema de la muestra fue seleccionado por la saturación del discurso por un total de 12 DM usuarios que realizan la AMGC en casa. Resultados: el análisis del contenido de los datos permitió identificar tres categorías: realización de AMGC no racional; La ausencia de programas educativos para orientar en la realización de AMGC; Disponibilidad insuficiente de insumos a los usuarios que realizan AMGC. Conclusión: A pesar de los avances alcanzados legalmente por las políticas públicas, usuarios con DM desconocen la legislación y cómo está directamente interfiere en la AMGC de conducta

Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus).

Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityus serrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64 Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1 µg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60 min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1 µg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C.

Antinociceptive and wound healing activities of Croton adamantinus Müll. Arg. essential oil.

Leaves of Croton adamantinus have been used to treat inflammation and skin wounds in the semi-arid area of the Northeast of Brazil. In order to evaluate if the essential oil (EO) was responsible for the claimed activities; antinociceptive, wound healing and antimicrobial tests were carried out. Twenty constituents were identified in C. adamantinus EO by GC-MS, ¹H-NMR and ¹³C-NMR, the major compounds being methyl-eugenol (14.81%) and 1,8-cineol (13.74%). Antinociceptive activity was evaluated by the formalin test and the abdominal contortion assay in mice. The EO (50 and 100 mg/kg) decreased the licking time of both phases of the formalin test when compared to the vehicle, but not to morphine (7.5 mg/kg). In the abdominal contortion assay, the EO (50 and 100 mg/kg) reduced the number of contortions compared to the vehicle and to indometacin (10 mg/kg). The wound healing activity was verified also using two experimental models: excisional wound and dead space. Topical treatment with the EO (1%) increased the wound contraction from the third day of treatment (compared with nitrofurazone 0.2%), while systemic treatment (50 mg/kg/day) increased granulation tissue formation and reduced the water content. C. adamantinus EO also showed antimicrobial activity against Staphylococcus aureus in disk diffusion method. These results corroborate the ethnobotanical use of this specie by Brazilian population.