NMR and multivariate methods: Identification of chemical markers in extracts of pedra-ume-caá and their antiglycation, antioxidant, and enzymatic inhibition activities.

INTRODUCTION: In Brazil, the plant group popularly known as "pedra-ume-caá" is used in folk medicine for the treatment of diabetes, and its raw material is commonly sold. OBJECTIVE: The aim of the study was to apply a method for chemical identification of extracts of dry pedra-ume-caá leaves using HPLC-high-resolution mass spectrometry (HRMS) and NMR and develop a multivariate model with NMR data to authenticate commercial samples. In addition, to evaluate the biological activities of the extracts. MATERIALS AND METHODS: Dry extracts of Myrcia multiflora, Myrcia amazonica, Myrcia guianensis, Myrcia sylvatica, Eugenia punicifolia leaves, and 15 commercial samples (sold in Manaus and Belém, Brazil) were prepared by infusion. All the extracts were analysed using HPLC-high-resolution mass spectrometry (HRMS), NMR, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The antidiabetic effect of extracts was evaluated according to enzymatic inhibition. Their content of total phenols, cell viability, and antioxidant and antiglycation activities were also determined. RESULTS: HPLC-HRMS and NMR analysis of these extracts permitted the identification of 17 compounds. 1H NMR data combined with multivariate analyses allowed us to conclude that catechin, myricitrin, quercitrin, and gallic and quinic acids are the main chemical markers of pedra-ume-caá species. These markers were identified in 15 commercial samples of pedra-ume-caá. Additionally, only the extracts of M. multiflora and E. punicifolia inhibited α-glucosidase. All the extracts inhibited the formation of advanced glycation end products (AGEs) and showed free-radical-scavenging activity. These extracts did not present cytotoxicity. CONCLUSION: This study revealed the chemical markers of matrices, and it was possible to differentiate the materials marketed as pedra-ume-caá. Moreover, this study corroborates the potential of these species for treating diabetes.

Recovery and partial purification of fibrinolytic protease from Pleurotus ostreatus and P. eryngii and cytotoxic and antioxidant activity of their extracts.

Mushrooms are a source of primary and secondary metabolites. Little is known about the most suitable conditions for production of mushrooms by submerged fermentation. This article reports antioxidant and cytotoxic assays, in addition to quantitatively evaluating the content of proteases with fibrinolytic action in the crude extracts of two species of edible mushrooms produced in different formulations, as well as evaluating the recovery of these enzymes by aqueous two-phase systems (ATPS). The mushrooms Pleurotus ostreatus and Pleurotus eryngii, at concentration of 100 µg/mL, displayed inhibition of DPPH and ABTS radicals below 50%. In the cytotoxicity test, the cells human fibroblast cell lines (MRC-5) showed cell viability greater than 80%. Concerning fibrinolytic activity, P. eryngii presented 226.47 ± 7.26 U/mL, therefore being more efficient than P. ostreatus (71.5 ± 0.56 U/mL). In the recovery of the P. eryngii extract by ATPS, the fibrinolytic protease was partitioned in the salt phase (30.25 U/mL). The molecular mass of the proteases was between 75 and 100 kDa. These results prove the low cytotoxicity of the extracts produced and that fermentation in supplemented malt broth favored the excretion of fibrinolytic proteases compared to the other evaluated media.

Effect of chia flour associated with high fat diet on intestinal health in female ovariectomized Wistar rats.

PURPOSE: The present study aimed to evaluate the effect of chia flour associated with a high fat diet on intestinal health in female ovariectomized Wistar rats. METHODS: The study was conducted with 32 adult female ovariectomized Wistar rats, which were separated into four groups: standard diet (ST), standard diet with chia (STC), high fat diet (HF) and high fat diet with chia (HFC) for 18 weeks. Cecum content pH, short chain fatty acid content, brush border membrane functionality and morphology and the gut microbiota were evaluated. RESULTS: This study demonstrated that the consumption of chia flour increased the production of acetic and butyric acids, the longitudinal and circular muscle layers and crypt thickness. It also improved the expression of aminopeptidase (AP) and sucrose-isomaltase (SI) and decreased the cecum content pH. Further, the consumption of chia improved richness and decreased diversity of the microbiota. Operational Taxonomic Units (OTUs) clustering indicated difference between the ST and STC groups. In the linear discriminant analysis effect size (LEfSe) analysis, the Bacteroides genus and members of the Muribaculaceae and Lachnospiraceae families were enriched in the STC treatment group. The STC group demonstrated the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways related to peptidoglycan and coenzyme A biosynthesis. CONCLUSION: Our results suggest that chia flour, which is rich in dietary fiber and phenolic compounds, presented potential properties to improve intestinal health.

Sorghum flour BRS 305 hybrid has the potential to modulate the intestinal microbiota of rats fed with a high-fat high-fructose diet.

AIM: The present study aimed to investigate the effect of dry heated whole sorghum BRS 305 hybrid flour on the gut microbiota modulation and gut health of rats fed with a high-fat high-fructose diet (HFHF). METHODS: In phase I (8 weeks), 45-50 days, male Wistar rats, were separated into the AIN93-M group (n = 10; fed with normal diet) and HFHF group (n = 20; fed with diet rich in saturated and simple carbohydrate). In phase II (10 weeks), we maintained the AIN-93-M group, and the HFHF group was divided into the HFHF group (n = 10) and HFHF plus sorghum flour group (n = 10). RESULTS: The consumption of sorghum flour increased the circular muscle layer and propionic acid when compared to the HFHF group. The sequencing of the 16S rRNA gene of the cecal microbiota presented no changes in the α-diversity and ß-diversity between. However, the sorghum group exhibited higher relative abundance of Firmicutes and higher Firmicutes/Bacteroidetes ratio compared to the other experimental groups, and lower abundance of Bacteroidetes, compared to the HFHF group. Despite, sorghum increased the abundance of the genera Roseburia and Lachnospiraceae_NK4A136_group compared to the HFHF group. No differences were observed in total goblet cell number, crypt thickness and height, circular muscle layer, secretory IgA, and butyric acid between all groups. CONCLUSIONS: The consumption of sorghum flour can modulate the gut microbiota composition, abundance of SCFA-producing bacteria, and intestinal morphology even with consumption of an HFHF diet.

Regulation of dental consultations in primary health care and performance of services in dental speciality centers.

OBJECTIVE: This study analyzed the regulation of dental specialty centers (CEOs) coordinated exclusively by Primary Health Care (PHC) in four primary outcomes: access and dental consultation, reception services, bonding and responsibility, and social participation. METHODS: A cross-sectional study was carried out using secondary data from the National Program for the Improvement of Access and Quality of Dental Specialty Centers (PMAQ-CEO): second cycle, using multilevel logistic regression to calculate the odds ratio (OR) and individual covariates. RESULTS: The analytical sample consisted of 9,599 CEO users who had completed all the variables analyzed. Of these, 63.5% were referred to the CEO by PHC. Dental care regulated by PHC was related to better access (OR 1.36, CI 95% 1.10-1.68), better reception (OR 1.33, CI 95% 1.03-1.71), better bonding and responsibility (OR 1.36, CI 95% 0.91-2.04), and social participation (OR 1.13, CI 95% 0.93-1.35) compared to those not regulated by primary health care as the exclusive pathway. CONCLUSION: The regulation of access to the CEO coordinated by PHC presented the best performance. It is suggested that this form of PHC regulation, as a route for dental specialty centers, can be established in the national oral health care policy for better service performance.

Decomposition and nutrient release of green manure biomass in a passion fruit orchard in the brazilian semiarid region.

Green manure decomposition and nutrient recycling improve soil quality and productivity of different crops, but information on irrigated fruit orchards in the Brazilian semi-arid region is still scarce. Decomposition and nitrogen, phosphate, and potassium release from the cut biomass of three green manure legumes (sunn hemp, pigeon pea and jack bean) placed in litterbags, and spontaneous vegetation grown for 90 days in the rows of a passion fruit orchard were followed for 150 days. Biomasses decreased exponentially, reaching 12 (sunn hemp) to 25% (jack beans and spontaneous vegetation) after 150 days. K was rapidly released (< 21 and 4% of the original content remaining after 7 and 150 days, respectively), contrasting with more than half of the P and one third of the N remaining after 150 days. The amounts released were more influenced by the amounts of biomass produced (sunn hemp, 1583); (Jack bean 5152 kg ha-1); (Pigeon pea 822 kg ha-1); (Spontaneous plants 3175 kg ha-1); (spontaneous legumes 744 kg ha-1) than by variation in decomposition proportions among species. N release represented a liquid input to the soil, since more than 80% of the green manure and spontaneous vegetation contents came from N2-symbiotic fixation. Therefore, green manure is an effective technique to incorporate N and recycle K and P in irrigated orchards in the Brazilian semi-arid region.

Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells.

Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo-induced cellular network (iNet) 'webs', which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.

Bioavailability of Calcium from Chia (Salvia hispanica L.) in Ovariectomized Rats Fed a High Fat Diet.

BACKGROUND: Skeletal abnormalities such as bone loss occur when there is an imbalance in bone matrix synthesis and bone resorption. This imbalance is also caused by hormonal changes and inflammation. Chia (Salvia hispanica L.) has a high nutritional value and is an excellent source of calcium. Evaluate the bioavailability of calcium from chia, and its effect on bone metabolism when consumed as part of a standard or high fat diet (HFD) in ovariectomized rats. METHODS: The study was conducted with 80 female Wistar rats that received standard diet or HFD. 40 female mice were ovariectomized (OVX) and 40 were sham-operated (SHAM). After recovery from surgery the animals received chia as a source of 20% of the calcium recommendation, calcium bioavailability was measured using the calcium balance technique. Bone strength and bone morphometry were evaluated by weight, length and microtomography measurements. RESULTS: HFD increased serum calcium and decreased calcium retention. The addition of chia to HFD did not alter bone morphology. Ovariectomy led to lower percentage of bone volume, smaller trabecular thickness, higher trabecular separation and higher porosity, when ovariectomy was associated with HFD, the final weight, waist circumference, body mass index and adiposity were increased. CONCLUSIONS: Chia maintained bone health when offered as a source of 20% calcium, in a diet that met 100% of the mineral recommendation, regardless of the type of diet, in animals non-ovariectomized adults.

Polymorphisms and haplotypes in the Interleukin 17 Alfa gene: potential effect of smoking habits in the association with periodontitis and type 2 diabetes mellitus.

Few studies evaluate interrelationships between periodontitis (P) and Type 2 Diabetes Mellitus (T2DM). The aim of this study is to investigate the genetic susceptibility to periodontitis alone, or concomitant with T2DM (as comorbidities), analyzing single nucleotide polymorphisms (SNPs) in the Interleukin 17 alpha (IL17A) gene, considering the biochemical profile and smoking habits on the subjects' periodontal status. We investigated 879 individuals divided into: T2DM subjects also affected by severe or moderate periodontitis (T2DM-P, n = 199); non-diabetics with severe or moderate periodontitis (PERIODONTITIS, n = 342); and healthy subjects (HEALTHY, n = 338). Subjects underwent complete periodontal examination, history of smoking habits, glycemic and lipid biochemical evaluation. DNA from buccal cells was utilized to genotype the SNPs rs2275913, rs3819024 and rs10484879. The impact of the subjects' biochemical profile was analyzed in their periodontal status. Each SNP was analyzed independently, and as haplotypes, by multiple logistic regressions, adjusted for covariates, and also stratifying the groups by age, sex and smoking habits. Independently of the periodontitis degree, poorly-controlled T2DM subjects showed worse glycemic and lipid profile. Multiple logistic regressions demonstrated that smokers and former-smokers carrying the GG genotype of rs3819024 seemed to have higher risk for T2DM-Periodontitis (OR = 6.33; 95% CI = 1.26-31.77, p = 0.02), and mainly for T2DM alone (OR = 5.11; 95% CI = 1.37-19.06, p = 0.01), than never smokers. We found the potential effect of smoking habits in the association of IL17A-rs3819024-GG with diseased phenotypes. Because the observed wide confidence intervals, further studies enrolling larger populations, and SNPs' functional evaluations are needed to better understand our findings.

Physicochemical Characterization, Stability and Cytotoxicity of a Blue Dye Obtained from Genipap Fruit (Genipa americana L.).

RESEARCH BACKGROUND: The current commercial scenario indicates an increase in the demand for natural dyes. Compared to synthetic dyes, natural ones have the advantage of being sustainable, making them of great interest for the food and cosmetic industries. The development of new natural dyes is necessary, as well as the carrying out of complementary research regarding the existing ones. EXPERIMENTAL APPROACH: The present study aims to characterize the physicochemical and biological characteristics of the dye obtained from dehydrated endocarp of the genipap (Genipa americana) fruit, as well as perform the relevant stability and cytotoxicity tests. The chemical characterization was performed by HPLC-MS/MS analyses. The stability studies were carried out by spectrophotometry and cytotoxicity assays using cell culture and fluorometric methods. RESULTS AND CONCLUSIONS: After dehydration and milling of the fruit endocarp, water was added to the obtained powder (in the ratio 4:1) to extract the dye. Five compounds were elucidated using HPLC-MS/MS and confirmed the presence of the geniposide as its main compound. With the X-ray diffraction and electron microscopy analysis, we characterised the obtained powder as being amorphous and of porous structure with a variable size. The thermogravimetric analysis indicated a maximum loss of 61% mass after exposure to a temperature range from 240 to 760 °C. The obtained blue dye was stable in the absence of light, at room temperature and had neutral pH. In the cytotoxicity assay, (95.0±1.3) % of viable human fibroblasts were observed after exposure to this dye. The genipap fruit can be a viable alternative to produce a natural blue dye, since it is easy to obtain and has very low toxicity in food, pharmaceutical or cosmetic products. NOVELTY AND SCIENTIFIC CONTRIBUTION: This study demonstrates for the first time the physicochemical and biological properties of a natural blue dye from G. americana fruit.

Macrobrachium amazonicum (Crustacea, Decapoda) Used to Biomonitor Mercury Contamination in Rivers.

Open-air landfill's may be are considered as a potential source of human environmental exposure to chemical substances such as, polycyclic aromatic hydrocarbons and toxic metals. Due to possible availability of mercury in the environment caused by open landfill emissions, this study evaluates the spatiality and seasonality of macroinvertebrates, in particular shrimps (Macrobrachium amazonicum), exposure to mercury (Hg). Information regarding Hg accumulation in this crustacean may be important for the development of public policies aiming conservation and preservation of ecosystems surrounding landfills in Amazon, and around the world. Sampling occurred quarterly in the following months: November/2015; February/2016; May/2016 and; August/2016. In each of these months, three points were selected: P1, P2 and P3. The samples were processed via acid digestion and the quantification of metal was performed by inductively coupled plasma mass spectrometry. The average concentration of total mercury (T-Hg) was 24.565 ± 6.610 µg kg-1 wet weight, with minimum and maximum limits of 12.742 ± 11.367 (P3) and 35.509 ± 14.761 µg kg-1 wet weight (P1) in November/2015 and August/2016, respectively. The concentration of total mercury (T-Hg) in shrimps was different between points (p = 0.004) and months (p = 0.000). The T-Hg concentrations were significantly higher in May and August 2016, which corresponds to the dry season. The presence of landfills promotes large accumulation of T-Hg in the aquatic biota and represents a risk to human health. However, seasonal changes in T-Hg levels were observed. In the wettest period, bioconcentration factor levels decrease in aquatic organisms.

Müller Cells Derived from Adult Chicken and Mouse Retina Neurospheres Acquire the Dopaminergic Phenotype.

Neurospheres prepared from multipotent progenitors in the retina obtained from postnatal mice differentiate into neurons and Müller glia (De Melo Reis et al., in Cell Mol Neurobiol 31:835-846, 2011). Here, we investigated whether neurospheres prepared from adult chickens (ciliary marginal zone, CMZ) or (ciliary body) retina could also lead to differentiated neurons and glia. Neurospheres were prepared from post-hatched chickens or from adult mice after 7 days in the presence of mitogenic factors (FGFb, insulin, and EGF), generating neurons and glial cells. In addition, Müller (2M6 or glutamine synthetase positive cells) derived from post-hatch chicken CMZ neurospheres displayed the dopaminergic phenotype. Furthermore, we observed that Müller cells derived from adult chickens and mice retina neurospheres released significant amounts of dopamine as well as of its metabolites. Taken together, our data lead us to conclude that as for embryonic (chick) or newborn (mouse), the dopaminergic phenotype is a default condition of Müller glial cells obtained from neurospheres prepared from mature retina. Our data raise the possibility that Müller cells from differentiated tissue could be used to ameliorate neurodegenerative diseases involving dopaminergic dysfunction as in Parkinson's disease as shown previously (Stutz et al., in J Neurochem 128:829-840, 2014).

Effects of blueberry and cranberry consumption on type 2 diabetes glycemic control: A systematic review.

The metabolic effects of cranberry and blueberry consumption on glycemic control have been evaluated in vitro and in animal models as well as in human studies, although findings have not been systematically reviewed yet. Therefore, a systematic review was carried out of relevant randomized clinical trials (RCTs) in order to assess the effect of berries (blueberry and cranberry) consumption on type 2 diabetes (T2DM) glycemic control. Some evidences were also discussed on the anti-diabetic mechanisms exerted by berries polyphenols. Studies were identified by searching electronic databases: LILACS, PubMed/MEDLINE, Scopus, The Cochrane Library and Web of Science. Three authors independently searched and extracted RCTs in which the effect of berries (cranberry or blueberry) consumption on T2DM glycemic control was assessed. A total of 7 RCTs, involving 270 adults with type 2 diabetes were included. Despite the heterogeneity of the administration forms (in natura, dried, extract, preparations - juice), dosage, duration of the intervention and type of population of the studies involving these two berries some studies highlight the potential benefit of berries, especially of blueberry, on glucose metabolism in T2DM subjects. Daily cranberry juice (240 mL) consumption for 12 weeks and blueberry extract or powder supplementation (9.1 to 9.8 mg of anthocyanins, respectively) for 8 to 12 weeks showed a beneficial effect on glucose control in T2DM subjects. Those results indicate a promising use of these berries in T2DM management; although more studies are required to better understand the mechanisms involved.

A Combined Computer-Aided Approach to Drive the Identification of Potential Epitopes in Protein Therapeutics.

BACKGROUND: The identification of fragment sequences, or motifs, within a therapeutic protein that may elicit an immune response when processed by T-cells can be provided by computer-aided approaches. Immunogenicity is a significant problem associated with protein therapeutics and should be investigated in the early stage of protein-based drug development to avoid treatment resistance and potentially life-threatening immune responses. PURPOSE: To provide a combined computer-aided protocol for investigating the immunogenic profile of a recombinant Kunitz-type inhibitor, which has been reported as promising antitumor agent by our research group. METHODS: The combination of databases searching (IEDB and SYFPEITHI) and molecular docking simulations was exploited, herein. This combined protocol has allowed the identification of potential epitopes before in vitro/in vivo evaluation. Predictors of human proteasome cleavage transport and major histocompatibility complex (MHC) binding were considered as overall score assigning the corresponding intrinsic potential of being a T cell epitope to each fragment sequence. The peptides or motifs better classified in the two databases were docked into the three-dimensional (3D) structure of MHC (class I and II) complex to verify the calculated binding affinity.  The binding interactions regarding the molecular recognition process by T-cells were also exploited through the MHC:ligand:T-cell complexes. RESULTS: Regarding the Kunitz-type sequence, four motifs were identified as potentially epitopes for MHC-I and three motifs were found for MHC-II. But, those motifs were classified as moderately immunogenic. Final remarks: The combined computer-aided protocol has significantly reduced the number of potential epitopes to be considered for further analysis and could be useful to identify immunogenic fragments (high, moderate and low) in protein pharmaceutics before in vitro/in vivo experimentation.

Towards Understanding Male Infertility After Spinal Cord Injury Using Quantitative Proteomics.

The study of male infertility after spinal cord injury (SCI) has enhanced the understanding of seminal plasma (SP) as an important regulator of spermatozoa function. However, the most important factors leading to the diminished sperm motility and viability observed in semen of men with SCI remained unknown. Thus, to explore SP related molecular mechanisms underlying infertility after SCI, we used mass spectrometry-based quantitative proteomics to compare SP retrieved from SCI patients to normal controls. As a result, we present an in-depth characterization of the human SP proteome, identifying ∼2,800 individual proteins, and describe, in detail, the differential proteome observed in SCI. Our analysis demonstrates that a hyper-activation of the immune system may influence some seminal processes, which likely are not triggered by microbial infection. Moreover, we show evidence of an important prostate gland functional failure,i.e.diminished abundance of metabolic enzymes related to ATP turnover and those secreted via prostasomes. Further we identify the main outcome related to this fact and that it is intrinsically linked to the low sperm motility in SCI. Together, our data highlights the molecular pathways hindering fertility in SCI and shed new light on other causes of male infertility.

Spermatic mitochondria: role in oxidative homeostasis, sperm function and possible tools for their assessment.

SummaryDespite sperm mitochondrial relevance to the fertilization capacity, the processes involved in the production of ATP and functional dynamics of sperm mitochondria are not fully understood. One of these processes is the paradox involved between function and formation of reactive oxygen species performed by the organelle. Therefore, this review aimed to provide data on the role of sperm mitochondria in oxidative homeostasis and functionality as well the tools to assess sperm mitochondrial function.

Polyunsaturated fatty acids and type 2 diabetes: Impact on the glycemic control mechanism.

There is a growing mortality related to co-morbidities associated with diabetes mellitus. Intake of polyunsaturated fatty acids (PUFA) has been associated with low cardiometabolic risk and reduction of inflammatory process. The objective of this paper is to review the impact of PUFA intake on glycemic control in diabetic patients as well as to elucidate the possible mechanisms involved. Medline/PubMed electronic database was searched to identify studies published within last five years regarding the effect of PUFA intake on glucose metabolism in type 2 diabetics. The search terms used were "polyunsaturated fatty acid(s)," "PUFA," and "diabetes." We included only interventional studies that assessed the effects of PUFA intake on glucose metabolism - fasting glucose, serum insulin, HbA1c, and HOMA-IR assessment- in type 2 diabetics. Initially, 48 articles were identified, of which one was not available and 41 did not match the inclusion criteria. Within the selected studies, three articles showed an improvement in fasting blood glucose, two showed an increase in fasting glycemia, and there was no effect of intervention in one article only. Based on the analyzed clinical interventional studies, supplementation of 0.42-5.2-g PUFA/day for at least eight weeks may become an alternative treatment for type 2 diabetes mellitus, particularly in Asian subjects.

Association between vitamin deficiency and metabolic disorders related to obesity.

Inappropriate food behavior contributes to obesity and leads to vitamin deficiency. This review discusses the nutritional status of water- and fat-soluble vitamins in obese subjects. We verified that most vitamins are deficient in obese individuals, especially the fat-soluble vitamins, folic acid, vitamin B12 and vitamin C. However, some vitamins have been less evaluated in cases of obesity. The adipose tissue is considered a metabolic and endocrine organ, which in excess leads to changes in body homeostasis, as well as vitamin deficiency which can aggravate the pathological state. Therefore, the evaluation of vitamin status is of fundamental importance in obese individuals.

The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist.

5'-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 1-12 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist. Locomotor and motor activities were not affected by PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent time in the open arms of the apparatus compared with the control group. Conversely, a decrease in the percentages of entries and time spent in the closed arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist, prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB 8 exhibited antinociceptive activity in the hot plate test, and reduced reactivity to formalin in the neurogenic and the inflammatory phases. These data suggest that PILAB 8 can activate µ-opioid receptors to provoke antinociceptive and anti-inflammatory effects in mice.

Empathy is Associated with Meaning of Life and Mental Health Treatment but not Religiosity Among Brazilian Medical Students.

The purpose of this study was to investigate the influence of spirituality, religiosity, personal beliefs, and previous contact with health issues on the level of empathy in medical students. Jefferson Scale of Empathy-Student Version, WHOQOL-Spirituality, Religiousness and Personal Beliefs, and Duke University Religion Index were applied to 285 Brazilian medical students. The findings suggest that meaning of life and previous mental health treatment but not Religiosity were positively related to empathy. We suggest that more attention should be given for prevention and treatment of mental health issues, and further studies are needed to understand and replicate these findings.