Antifungal activity of terpenes isolated from the Brazilian Caatinga: a review.

Terpenoids, also named terpenes or isoprenoids, are a family of natural products found in all living organisms. Many plants produce terpenoids as secondary metabolites, and these make up a large part of essential oils. One of most important characteristic is that the compounds are volatile, have odor and can be used in a variety of applications in different industrial segments and traditional medicine. Brazil has a rich and diverse flora that can be used as a source of research for obtaining new molecules. Within the Brazilian flora, it is worth mentioning the Caatinga as an exclusively Brazilian biome where plants adapt to a specific series of weather conditions and therefore become a great storehouse of the terpenoid compounds to be described herein. Fungal infections have become increasingly common, and a great demand for new agents with low toxicity and side effects has thus emerged. Scientists must search for new molecules exhibiting antifungal activity to develop new drugs. This review aims to analyze scientific data from the principal published studies describing the use of terpenes and their biological applications as antifungals.

Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury.

Yellow fever (YF) is a mosquito-transmitted viral disease that causes tens of thousands of deaths each year despite the long-standing deployment of an effective vaccine. In its most severe form, YF manifests as a hemorrhagic fever that causes severe damage to visceral organs. Although coagulopathy is a defining feature of severe YF in humans, the mechanism by which it develops remains uncertain. Hepatocytes are a major target of yellow fever virus (YFV) infection, and the coagulopathy in severe YF has long been attributed to massive hepatocyte infection and destruction that results in a defect in clotting factor synthesis. However, when we analyzed blood from Brazilian patients with severe YF, we found high concentrations of plasma D-dimer, a fibrin split product, suggestive of a concurrent consumptive process. To define the relationship between coagulopathy and hepatocellular tropism, we compared infection and disease in Fah-/-, Rag2-/-, and Il2rɣ-/- mice engrafted with human hepatocytes (hFRG mice) and rhesus macaques using a highly pathogenic African YFV strain. YFV infection of macaques and hFRG mice caused substantial hepatocyte infection, liver damage, and coagulopathy as defined by virological, clinical, and pathological criteria. However, only macaques developed a consumptive coagulopathy whereas YFV-infected hFRG mice did not. Thus, infection of cell types other than hepatocytes likely contributes to the consumptive coagulopathy associated with severe YF in primates and humans. These findings expand our understanding of viral hemorrhagic disease and associated coagulopathy and suggest directions for clinical management of severe YF cases.

Online dating, reproductive success and the rise autism spectrum disorder prevalence.

The increase in the prevalence of autism spectrum disorder (ASD) has not yet been adequately explained. There is evidence that when people with a specific personality profile, including strong systematic thinking, attention to detail and lesser social communication skills, though not falling on the autistic spectrum (AS), are more likely to have children with autism, especially when both parents have such characteristics. The use of new technologies such as social networks facilitates the communication of these persons because it does not rely on skills in which they are deficient. We hypothesize that the massive use of such technologies for the establishment of romantic relationships increases the reproductive success of this population contributing to the increase in the prevalence of autism spectrum disorder.

Rethinking priorities: experience of an educational initiative to change attitudes, behaviours and clinical practice in end-of-life care.

To implement the National End of Life Care strategy and enable more people to express and achieve their preferences about care at the end of life, senior clinicians outside palliative medicine need to make it a routine part of their practice. However, it is acknowledged that recognising that people are entering the last phase of their illness is not always straightforward, and having conversations about aims of treatment and planning for future care may not be easy. In order to begin to address these challenges, funding was sought from the Yorkshire and the Humber Strategic Health Authority (SHA), and subsequently Health Education England, Yorkshire and the Humber (HEEYH), to pilot a development programme in 2 acute trusts. 2 palliative medicine consultants shared the trainer role at each site, supporting hospital consultants from a range of specialties, with a GP to give a community perspective. The programme involved individual clinicians identifying their own learning needs and specific issues for end-of-life care in their patients. The group met together monthly in action learning sets to discuss issues in a safe yet challenging environment. Following evaluation using a combination of training needs analyses, feedback questionnaires, audits and service evaluations, it was modified slightly and repiloted in 2 further trusts as 'Rethinking Priorities'. This paper describes the programme and its outcomes, especially in relation to participants' learning, service development and leadership. It also highlights the challenges, including different learning styles, the concept of action learning, obtaining funding and dedicated time, and how to evaluate the effectiveness of a programme. Overall, it suggests that an educational initiative based on clinicians identifying their own learning needs, and using an action learning approach to explore issues with other colleagues, with the addition of some targeted sessions, can result in positive change in knowledge, behaviour and clinical practice.

Neurotoxicity in zebrafish exposed to carbon nanotubes: Effects on neurotransmitters levels and antioxidant system.

Given the increasing use of carbon nanotubes (CNT) in several industries and technological applications, it is essential to perform in vivo toxicological studies with these nanomaterials to evaluate their potential ecotoxicity. Dopamine (DA) and serotonin (5HT) are key neurotransmitters for brain functions and behavioral responses. Determination of DA and 5HT were performed in brain samples from zebrafish Danio rerio exposed i.p. to single-walled CNT (SWCNT), besides analyzing acetylcholinesterase (AChE) and ectonucleotidases activity, lipid peroxidation and total antioxidant capacity. Results showed that treatment with SWCNT increased between 3 and 6-fold the concentration of DA and 5HT (p < 0.05). Similarly, a significant reduction (p < 0.05) in AChE activity was observed in the brains of SWCNT exposed zebrafish when compared to the control groups. Cholinergic, serotonergic, and dopaminergic systems, through AChE activity and serotonin and dopamine levels, respectively were affected by SWCNT in the zebrafish brain. Alterations in these neurotransmitters can potentially affect several physiological and behavioral that they control.

Experimental Fock-State Superradiance.

Superradiance in an ensemble of atoms leads to the collective enhancement of radiation in a particular mode shared by the atoms in their spontaneous decay from an excited state. The quantum aspects of this phenomenon are highlighted when such collective enhancement is observed in the emission of a single quantum of light. Here we report a further step in exploring experimentally the nonclassical features of superradiance by implementing the process not only with single excitations, but also in a two-excitation state. Particularly, we measure and theoretically model the wave packets corresponding to superradiance in both the single-photon and two-photon regimes. Such progress opens the way to the study and future control of the interaction of nonclassical light modes with collective quantum memories at higher photon numbers.

Testicular thermoregulation, scrotal surface temperature patterns and semen quality of water buffalo bulls reared in a tropical climate.

This study evaluated the capacity of thermoregulation and its consequences on the scrotal surface temperature patterns and semen quality of buffalo bulls raised in a wet tropical climate. Eleven water buffaloes were evaluated in the rainiest, in the transitional and in the less rainy season. Air temperature and humidity were consistently high, but the animals did not show thermal stress in any season. The scrotal temperature gradient of buffalo bulls using infrared thermography was described, and three parallel and decreasing thermal bands were characterised. Sperm quality (n = 176 ejaculates) was maintained in normal parameters over the periods. Pearson's coefficients showed that sperm volume and progressive motility were negatively correlated with ocular globe, epididymal tail and minimum scrotal temperatures (p < .01). Sperm membrane integrity was negatively influenced by increases in epididymal tail and minimum scrotal temperatures (p < .01). Ocular globe temperature also showed positive correlation with rectal, spermatic cord, and epididymal tail temperatures (p < .01). Therefore, even under high temperature and humidity, the thermoregulatory system was effective in preventing heat stress and the normality of scrotal surface temperatures, spermatogenesis and sperm maturation were maintained.

Assessment of surface temperatures of buffalo bulls (Bubalus bubalis) raised under tropical conditions using infrared thermography / Avaliação de temperaturas superficiais de touros bubalinos (Bubalus bubalis) criados em ambiente tropical com uso da termografia infravermelha

This paper aimed to evaluate the surface temperatures of buffalo bulls using infrared thermography, considering four distinct anatomical parts over time, and to correlate surface temperatures and thermal comfort indexes. The humid tropical climate (Kõppen's Afi) was predominant in the research station where the experiment was performed and the trial lasted from April to August. Ten bulls (n=10) were evaluated every 25 days (morning: 6:00-9:00; afternoon: 12:00-15:00) and the parameters assessed were respiratory rate (RR), rectal temperature (RT), and the thermograms of surface temperature for orbital area (ORB), right flank (RF), left flank (LF) and scrotum (SCR). Climatological data was continuously monitored and the Temperature and Humidity Index (THI) and the Index of Comfort of Benezra (ICB) were calculated. The average values of THI were ≥78, and significant differences between shifts were observed (P<0.05). The ICB ranged from 1.96 to 2.25 and significant differences were observed for shifts and throughout the months (P<0.05). The averages of surface temperatures were RT=38.2±0.5°C, ORB=36.1±0.8°C, LF=33.5±2.5°C, RF=35.4±1.7ºC and SCR=33.3±1.1°C, which exhibited significant differences for shifts and throughout the months (P<0.05). Positive correlations were obtained between THI and ORB (0.72), RF (0.77), LF (0.75) and SCR (0.41) (P<0.0001). The maximum temperature of ORB showed the highest correlation with RT (0.58, P<0.0001). Therefore, the surface temperatures are subject to climatic variations and increase throughout the day, due to the variation in thermal comfort indexes, and the maximum ORB temperature was the parameter most related to rectal temperature. Lastly, the results indicate that IRT may be a useful non-invasive and accurate tool to detect the variations in ORB, LF, RF and SCR temperature in buffalo bulls.

O presente trabalho visou avaliar as temperaturas superficiais de diferentes regiões anatômicas de búfalos ao longo do tempo, por meio da termografia infravermelha, e correlacioná-las a índices bioclimatológicos de conforto térmico. O ensaio foi realizado em região de clima tropical úmido (Afi de Kõppen), de abril a agosto. Dez touros (n=10) foram avaliados a cada 25 dias (manhã: seis-nove horas; tarde: 12-15h), quanto à frequência respiratória (FR), temperatura retal (TR) e imagens termográficas da órbita ocular (ORB), flanco direito (FLd), flanco esquerdo (FLe) e escroto (ESC). Os dados climatológicos foram ininterruptamente monitorados, e calculados o índice de temperatura e umidade (ITU) e o índice de conforto de Benezra (ICB). O ITU foi ≥78, com diferença entre turnos (P<0,05). Já o ICB variou de 1,96 a 2,25 e apresentou diferenças ao longo dos meses e entre turnos (P<0,05). As temperaturas observadas foram de TR=38,2±0,5ºC, ORB=36,1±0,8ºC, FLd=33,5±2,5ºC, FLe=35,4±1,7ºC e ESC=33,3±1,1ºC, as quais variaram significativamente ao longo dos meses e entre turnos (P<0,05). O ITU apresentou correlações positivas com ORB (0,72), FLd (0,77), FLe (0,75) e ESC (0,41) (P<0,0001). A temperatura máxima de ORB apresentou a maior correlação com a TR (0,58; P<0,0001). Portanto, as temperaturas superficiais dos animais sofrem interferências das variações climáticas e se elevam ao longo do dia, devido à variação nos índices de conforto térmico; a temperatura máxima de ORB foi o parâmetro mais condicionado à temperatura retal. Também, as oscilações de temperatura de superfície de ORB, FLd, FLe e ESC podem ser aferidas em bubalinos com o uso da termografia infravermelha, de modo preciso e não invasivo.

Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats.

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

NMDA receptor binding in focal epilepsies.

OBJECTIVE: To demonstrate altered N-methyl-d-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [(18)F]GE-179, a ligand that selectively binds to the open NMDA receptor ion channel, which is thought to be overactive in epilepsy. METHODS: Eleven patients (median age 33 years, 6 males) with known frequent interictal epileptiform discharges had an [(18)F]GE-179 PET scan, in a cross-sectional study. MRI showed a focal lesion but discordant EEG changes in two, was non-localising with multifocal EEG abnormalities in two, and was normal in the remaining seven patients who all had multifocal EEG changes. Individual patient [(18)F]GE-179 volume-of-distribution (VT) images were compared between individual patients and a group of 10 healthy controls (47 years, 7 males) using Statistical Parametric Mapping. RESULTS: Individual analyses revealed a single cluster of focal VT increase in four patients; one with a single and one with multifocal MRI lesions, and two with normal MRIs. Post hoc analysis revealed that, relative to controls, patients not taking antidepressants had globally increased [(18)F]GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [(18)F]GE-179 VT (-29%; p<0.002). There were no focal abnormalities common to the epilepsy group. CONCLUSIONS: In patients with focal epilepsies, we detected primarily global increases of [(18)F]GE-179 VT consistent with increased NMDA channel activation, but reduced availability in those taking antidepressant drugs, consistent with a possible mode of action of this class of drugs. [(18)F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy.

Performance of an anthropometric assessment method as a predictor of low birthweight and being small for gestational age.

BACKGROUND: The present study aimed to evaluate the performance of the method proposed in 2009 by the Institute of Medicine for the anthropometric assessment of pregnant women, predicting perinatal outcomes: adequacy of birthweight, adequacy of birthweight according to gestational age [small for gestational age (SGA), large for gestational age (LGA)] and gestational and neonatal complications. METHODS: The study comprised a cross-sectional study involving 827 post-partum women (>20 years) who were treated in a public maternity hospital in the city of Rio de Janeiro. Data collection occurred by interviews and record consultation. Adequacy of weight gain during pregnancy was determined as being insufficient and excessive for the recommended range according to nutritional status category. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for logistic regression. RESULTS: Some 36.2% of women initiated gestation with some weight deviation. The prevalence of the outcomes studied was 4.6% (n = 35) for low birthweight, 3.7% (n = 31) for SGA, 5.7% (n = 47) for LGA, 45.2% (n = 374) for pregnancy complications and 15.2% (n = 85) for neonatal complications. For women with insufficient weight gain, the new recommendation indicated a correlation in the prediction of low birthweight (OR = 3.76, 95% CI = 1.53-9.21), SGA newborns (OR = 5.77, 95% CI = 2.10-15.8) and gestational complications (OR = 1.72, 95% CI = 1.20-2.48). CONCLUSIONS: The method evaluated demonstrated a better sensitivity and specificity for the main outcomes related to insufficient weight gain (low birthweight and SGA). Regarding excessive foetal growth (LGA), gestational and neonatal complications demonstrated sensitivity for an intermediate value.

Pharmacological blockage and P2X7 deletion hinder aversive memories: reversion in an enriched environment.

Adenosine triphosphate (ATP) plays a role in cell signaling. It was soon proposed that ATP activates ionotropic P2X receptors, exerting an influence on neurons as well as on glial cells. In addition to the fact that the activation of P2X and P2Y receptors can stimulate or inhibit the release of glutamate from rat hippocampal neurons, the release of ATP has been implicated in hippocampal long-term potentiation (LTP). Through different behavioral paradigms, this study aimed to investigate the participation of P2X7R in genetically modified (knockout (KO)) mice with the suppressed expression of this receptor and in the pharmacological blockage of this receptor in rats, as well as to evaluate the effect of environmental enrichment on potential mnemonic deficits. The results suggest that P2X7R participates in aversive memory processes: pharmacological blockage with the selective P2X7R antagonist, A-740003, in different time frames elicited dose-dependent impairments in memory acquisition, consolidation and retrieval in rats that were submitted to the contextual fear-conditioning (FC) task, and the deletion of P2X7R hampered the aversive memory processes of mice that were subjected to the FC paradigm. Experiments using mice that were subjected to environmental enrichment suggest that this form of stimulation reverses mnemonic impairments that are ascribed to the absence of the P2X7R, suggesting that these receptors do not participate on such a reversal. Finally, no alterations were observed in the habituation memory of P2X7KO mice.

Possible impacts of climate change on wetlands and its biota in the Brazilian Amazon.

Wetlands cover approximately 6% of the Earth's surface. They are frequently found at the interface between terrestrial and aquatic ecosystems and are strongly dependent on the water cycle. For this reason, wetlands are extremely vulnerable to the effects of climate change. Mangroves and floodplain ecosystems are some of the most important environments for the Amazonian population, as a source of proteins and income, and are thus the types of wetlands chosen for this review. Some of the main consequences that can be predicted from climate change for wetlands are modifications in hydrological regimes, which can cause intense droughts or inundations. A possible reduction in rainfall can cause a decrease of the areas of mangroves and floodplains, with a consequent decline in their species numbers. Conversely, an increase in rainfall would probably cause the substitution of plant species, which would not be able to survive under new conditions for a long period. An elevation in water temperature on the floodplains would cause an increase in frequency and duration of hypoxic or anoxic episodes, which might further lead to a reduction in growth rates or the reproductive success of many species. In mangroves, an increase in water temperature would influence the sea level, causing losses of these environments through coastal erosion processes. Therefore, climate change will likely cause the loss of, or reduction in, Amazonian wetlands and will challenge the adaptability of species, composition and distribution, which will probably have consequences for the human population that depend on them.

Effects of isolation and environmental variables on fish community structure in the Brazilian Amazon Madeira-Purus interfluve.

Due to the existence of terrestrial barriers to freshwater fish dispersion, it is believed that its distribution is strongly associated with historical factors related to the formation of the habitats they occupy. By the other hand, some studies reveal the influence of abiotic conditions (such as size of water bodies, pH, conductivity) on the composition of fish fauna occurring in small streams. This study aimed to investigate whether drainage basins, because catchment boundaries are potential barriers to fish dispersion, or the physical structure and physico-chemical characteristics of water have a greater influence on fish community structure in small streams. We sampled 22 streams belonging to five drainage basins in the Madeira-Purus interfluve. Fish were caught with dip nets and a small trawl, and data were simultaneously obtained on structural characteristics of the streams and physico-chemical characteristics of the water. Community composition was analyzed using Non-Metric Multidimensional Scaling (NMDS), and variables related to structural and physico-chemical characteristics were summarized by Principal Component Analysis (PCA). Two explanatory models relating faunal composition to environmental factors were constructed: the first using only continuous variables and the second including the drainage basin as a categorical variable. The Akaike Information Criterion (AIC) and AIC weight were used to select the best model. Although structural and physico-chemical variables significantly contributed to explaining faunal composition, the model including the drainage basin was clearly the better of the two models (more than 90% support in the data). The importance of drainage basins in structuring fish communities in streams may have significant consequences for conservation planning in these environments.

Neuroactive effects of cotinine on the hippocampus: behavioral and biochemical parameters.

The present work evaluated the effects of nicotine (NIC), cotinine (COT), mecamylamine (MEC), methyllycaconitine (MLA) and dihydro-beta-eritroidine (DHßE) on memory extinction and the following biochemical parameters of the hippocampus: lipid peroxidation (LPO), antioxidant capacity (AC) and the phosphorylation of Extracellular-Signal-Regulated Kinase (ERK 1/2). Young male rats that were implanted bilaterally with cannulae were submitted to memory extinction tests sessions, and their hippocampi were dissected for biochemical assays. The extinction of fear memory was significantly improved by both nicotine and its metabolite. Cotinine significantly increased LPO, while nicotine significantly decreased it. Antioxidant capacity was increased by all treatments. Our results showed that cotinine, unlike nicotine, may increase oxidative stress in the hippocampus, but this increase depends upon the dose used and happens without causing corresponding impairments in cognitive function. Cotinine also increased the phosphorylation of ERK 1/2 in a similar fashion as nicotine. Considering these results, it is plausible to wonder to what extent nicotine-attributed effects are really due to the actions of this alkaloid and whether they could be due instead to cotinine or to cotinine-nicotine interactions within the brain.

Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus.

Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic monoterpene indole alkaloids. These compounds are able to display a large range of effects on the central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae) leaves, on monoamine levels in rat hippocampus and on monoamine oxidase activity. A significance (p<0.01) of 83.5% reduction in 5-HT levels was observed after intra-hippocampal injection (20 µg/µl). After treatment by intraperitoneal route (10 mg/kg), a 63.4% reduction in 5-HT levels and a 67.4% reduction in DOPAC values were observed. The results indicate that strictosidinic acid seems to act on 5-HT system in rat hippocampus, possibly inhibiting precursor enzymes of 5-HT biosynthesis. The decrease verified in DOPAC levels suggests a role of strictosidinic acid in the dopaminergic transmission, probably due to an inhibition of monoamine oxidase activity, confirmed by the enzymatic assay, which demonstrated an inhibitory effect on MAO A in rat brain mitochondria.