Mechanisms of the antinociceptive action of (?) Epicatechin obtained from the hydroalcoholic fraction of Combretum leprosum Mart & Eic in rodents

ABSTRACT: BACKGROUND: The mechanisms of the antinociceptive activity of () epicatechin (EPI), a compound isolated from the hydroalcoholic fraction of Combreum leprosum Mart & Eicher. METHODS: were assessed in the model of chemical nociception induced by glutamate (20 mumol/paw). To evaluate the mechanisms involved, the animals , male Swiss mice (25-30 g), received EPI (50 mg/kg p.o.) after pretreatment with naloxone (2 mg/kg s.c. opioid antagonist), glibenclamide (2 mg/kg s.c. antagonist K + channels sensitive to ATP), ketanserin (0.3 mg/kg s.c. antagonist of receptor 5-HT2A), yoimbine (0.15 mg/kg s.c. alpha2 adrenergic receptor antagonist), pindolol (1 mg/kg s.c. 5-HT1a/1b receptor antagonist), atropine (0.1 mg/kg s.c. muscarinic antagonist) and caffeine (3 mg/kg s.c. adenosine receptor antagonist), ondansetron (0.5 mg/kg s.c. for 5-HT3 receptor) and L-arginine (600 mg/kg i.p.). RESULTS: The antinociceptive effect of EPI was reversed by pretreatment with naloxone and glibenclamide, ketanserin, yoimbine, atropine and pindolol, which demonstrates the involvement of opioid receptors and potassium channels sensitive to ATP, the serotoninergic (receptor 5HT1A and 5HT2A), adrenergic (receptor alpha 2) and cholinergic (muscarinic receptor) systems in the activities that were observed. The effects of EPI, however, were not reversed by pretreatment with caffeine, L-arginine or ondansetron, which shows that there is no involvement of 5HT3 receptors or the purinergic and nitrergic systems in the antinociceptive effect of EPI. In the Open Field and Rotarod test, EPI had no significant effect, which shows that there was no central nervous system depressant or muscle relaxant effect on the results. CONCLUSIONS: This study demonstrates that the antinociceptive activity of EPI in the glutamate model involves the participation of the opioid system, serotonin, adrenergic and cholinergic.     

Heparin and its derivatives bind to HIV-1 recombinant envelope glycoproteins, rather than to recombinant HIV-1 receptor, CD4

We have employed a direct radiolabel binding assay to investigate the interaction between3H-heparin and recombinant envelope glycoproteins, rgp120s, derived from several different isolates of HIV-1. Comparable dose-dependent binding is exhibited by rgp120s from isolates IIIB, GB8, MN and SF-2. Under identical experimental conditions the binding of3H- heparin to a recombinant soluble form of the cellular receptor for gp120, CD4, is negligible. The binding of3H-heparin to rgp120 is competed for by excess unlabeled heparin and certain other, but not all, glycosaminoglycan and chemically modified heparins. Of a range of such polysaccharides tested, ability to compete with3H-heparin for binding was strictly correlated with inhibition of HIV-1 replication in vitro. Those possessing potent anti-HIV-1 activity were effective competitors, whereas those having no or little anti-HIV-1 activity were poor competitors. Scatchard analysis indicates that the K d of the interaction between heparin and rgp120 is 10 nM. Binding studies conducted in increasing salt concentrations confirm that the interaction is ionic in nature. Synthetic 33-35 amino acid peptides based on the sequence of the V3 loop of gp120 also bind to heparin with high affinity. V3 loop peptides that are cyclized due to terminal cysteine residues show more selective binding than their uncyclized counterparts. Overall, these data demonstrate further that heparin exerts its anti-HIV-1 activity by binding to the envelope glycoprotein of HIV-1, rather than its cellular receptor, CD4. This study confirms that the V3 loop of gp120 is the site at which heparin exerts its anti- HIV-1 activity. Moreover, it reveals that high affinity binding to heparin is shared by all four rgp120s examined, despite amino acid substitutions within the V3 loop.      

Care Seeking for Neonatal Illness in Low- and Middle-Income Countries: A Systematic Review

Background

Despite recent achievements to reduce child mortality, neonatal deaths continue to remain high, accounting for 41% of all deaths in children under five years of age worldwide, of which over 90% occur in low- and middle-income countries (LMICs). Infections are a leading cause of death and limitations in care seeking for ill neonates contribute to high mortality rates. As estimates for care-seeking behaviors in LMICs have not been studied, this review describes care seeking for neonatal illnesses in LMICs, with particular attention to type of care sought.

Methods and Findings

We conducted a systematic literature review of studies that reported the proportion of caregivers that sought care for ill or suspected ill neonates in LMICs. The initial search yielded 784 studies, of which 22 studies described relevant data from community household surveys, facility-based surveys, and intervention trials. The majority of studies were from South Asia (n = 17/22), set in rural areas (n = 17/22), and published within the last 4 years (n = 18/22). Of the 9,098 neonates who were ill or suspected to be ill, 4,320 caregivers sought some type of care, including care from a health facility (n = 370) or provider (n = 1,813). Care seeking ranged between 10% and 100% among caregivers with a median of 59%. Care seeking from a health care provider yielded a similar range and median, while care seeking at a health care facility ranged between 1% and 100%, with a median of 20%. Care-seeking estimates were limited by the few studies conducted in urban settings and regions other than South Asia. There was a lack of consistency regarding illness, care-seeking, and care provider definitions.

Conclusions

There is a paucity of data regarding newborn care-seeking behaviors; in South Asia, care seeking is low for newborn illness, especially in terms of care sought from health care facilities and medically trained providers. There is a need for representative data to describe care-seeking patterns in different geographic regions and better understand mechanisms to enhance care seeking during this vulnerable time period. Please see later in the article for the Editors'' Summary     

Co-development of wetland soils and benthic invertebrate communities following salt marsh creation

Wetlands Ecology and Management -     

Intra-amniotic prostaglandin F2α and urea for abortion

Prostaglandin F_2α (PGF_2α) 20 mg combined with urea 80 g was injected intra-amniotically in 20 patients to induce mid-trimester abortion. Abortion resulted in all subjects within 24 hours in a mean time of 12 hours 38 minutes (range 5 hours 50 minutes to 20 hours 45 minutes).Plasma sex steroids were evaluated before and hourly for 5 hours after the injection. A progressive decline in levels occurred with time. Decreases in plasma progesterone, estrone, estradiol and estriol were significant as soon as one hour after injection.Gastrointestinal side effects occurred with a greater frequency than when a comparable dose of PGF_2α is given alone and 2 patients had small cervical lacerations requiring suture. Further studies are indicated to establish whether a lower dose of PGF_2α will be associated with fewer side effects and be as effective.     

Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions

Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.     

Distinguishing epidemic waves from disease spillover in a wildlife population

Serengeti lions frequently experience viral outbreaks. In 1994, one-third of Serengeti lions died from canine distemper virus (CDV). Based on the limited epidemiological data available from this period, it has been unclear whether the 1994 outbreak was propagated by lion-to-lion transmission alone or involved multiple introductions from other sympatric carnivore species. More broadly, we do not know whether contacts between lions allow any pathogen with a relatively short infectious period to percolate through the population (i.e. reach epidemic proportions). We built one of the most realistic contact network models for a wildlife population to date, based on detailed behavioural and movement data from a long-term lion study population. The model allowed us to identify previously unrecognized biases in the sparse data from the 1994 outbreak and develop methods for judiciously inferring disease dynamics from typical wildlife samples. Our analysis of the model in light of the 1994 outbreak data strongly suggest that, although lions are sufficiently well connected to sustain epidemics of CDV-like diseases, the 1994 epidemic was fuelled by multiple spillovers from other carnivore species, such as jackals and hyenas.     

Sand goby (Pomatoschistus minutus) males exposed to an endocrine disrupting chemical fail in nest and mate competition

Endocrine disrupting chemicals (EDCs) are a widely studied group of chemicals that interfere with the endocrinology of organisms. So far, few studies have demonstrated the effect of EDCs on the reproductive behavior of aquatic wildlife. Here we show that sand goby males' (Pomatoschistus minutus) success in mating competition greatly decreases after an exposure for 7 to 24 days to 17α-ethinyl estradiol (EE2, measured concentration 4 ng L^− 1). The sand goby exhibits a polygynous mating system with male parental care, in which males compete for nest sites and females. The aim of this study was to test how EE2 exposure affects the ability of males to compete for breeding resources, i.e. nest sites and mates. First, EE2 exposed males competed over a nest site against a non-exposed, control male of the same size. Secondly, we examined male courtship behavior and female mate preferences for EE2 exposed males and similar-sized non-exposed, control males. In addition to the behavioral experiments we determined the zona radiata protein (Zrp) mRNA gene expression and measured morphometric indicators of sexual maturation. Our study revealed that EE2 treated males were not able to acquire or defend a nest site. Additionally, EE2 treated males spent significantly less time in active courtship and nest leading behavior than control males. As a result, females clearly preferred to mate with control males. However, we found no significant differences in Zrp mRNA expression or the morphometric indicators between treatments. Our study illustrates that exposure to this EDC can greatly reduce the chances of an individual reproducing successfully. Moreover, it demonstrates that severe behavioral effects can be seen before any effects are detectable at the molecular or morphometric level.