White Blood Cell Counts as Risk Markers of Developing Metabolic Syndrome and Its Components in the Predimed Study

Background

The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglucemia, hypertension, dyslipidemia and central obesity, conferring an increased risk of cardiovascular disease. The white blood cell (WBC) count has been proposed as a marker for predicting cardiovascular risk. However, few prospective studies have evaluated the relationship between WBC subtypes and risk of MetS.

Methods

Participants were recruited from seven PREDIMED study centers. Both a baseline cross-sectional (n = 4,377) and a prospective assessment (n = 1,637) were performed. Participants with MetS at baseline were excluded from the longitudinal analysis. The median follow-up was 3.9 years. Anthropometric measurements, blood pressure, fasting glucose, lipid profile and WBC counts were assessed at baseline and yearly during the follow-up. Participants were categorized by baseline WBC and its subtype count quartiles. Adjusted logistic regression models were fitted to assess the risk of MetS and its components.

Results

Of the 4,377 participants, 62.6% had MetS at baseline. Compared to the participants in the lowest baseline sex-adjusted quartile of WBC counts, those in the upper quartile showed an increased risk of having MetS (OR, 2.47; 95%CI, 2.03–2.99; P-trend<0.001). This association was also observed for all WBC subtypes, except for basophils. Compared to participants in the lowest quartile, those in the top quartile of leukocyte, neutrophil and lymphocyte count had an increased risk of MetS incidence. Leukocyte and neutrophil count were found to be strongly associated with the MetS components hypertriglyceridemia and low HDL-cholesterol. Likewise, lymphocyte counts were found to be associated with the incidence of the MetS components low HDL-cholesterol and high fasting glucose. An increase in the total WBC during the follow-up was also associated with an increased risk of MetS.

Conclusions

Total WBC counts, and some subtypes, were positively associated with MetS as well as hypertriglyceridemia, low HDL-cholesterol and high fasting glucose, all components of MetS.

Trial registration

Controlled-Trials.comISRCTN35739639.     

The thermoregulatory benefits of the communal nest of sociable weavers Philetairus socius are spatially structured within nests

Structures built by animals, such as nests, mounds and burrows, are often the product of cooperative investment by more than one individual. Such structures may be viewed as a public good, since all individuals that occupy them share the benefits they provide. However, access to the benefits generated by the structure may vary among individuals and is likely to be an important determinant of social organisation. Here we use the massive, communal nests of sociable weavers Philetairus socius, to investigate whether their thermoregulatory function varies in relation to the size of communal nests, and the position of individual nest chambers within the communal structure. We then examine whether this spatial variation in thermoregulatory function predicts the social organisation of colonies. First, we show that the sociable weavers’ communal nests buffer variation in ambient temperature, and reduce temperature variability within nest chambers. The extent of this buffering effect depends significantly on the position of nest chambers within the communal structure, and on the depth to which chambers are embedded within the nest mass. We detected no effect of nest volume on thermoregulatory benefits, suggesting that there are likely to be additional, non‐thermoregulatory benefits leading to communal nests. Finally, our results indicate that there may be competition for access to the benefits of the public good, since older birds occupied the chambers with the highest thermoregulatory benefits, where breeding activity was also more common. We discuss how the spatial structure of the benefits of the public good might influence social organisation in the unique communal lifestyle of sociable weavers.     

Purification of a chitin-binding protein from Moringa oleifera seeds with potential to relieve pain and inflammation

Moringa oleifera Lam. is a perennial multipurpose tree that has been successfully used in folk medicine to cure several inflammatory processes. The aim of this study was to purify and characterize a chitin-binding protein from Moringa oleifera seeds, named Mo-CBP4, and evaluate its antinociceptive and anti-inflammatory effects in vivo. The protein was purified by affinity chromatography on chitin followed by ion exchange chromatography. Acetic acid-induced abdominal constrictions assay was used for the antinociceptive and anti-inflammatory activity assessments. Mo-CBP4 is a glycoprotein (2.9% neutral carbohydrate) composed of two protein subunits with apparent molecular masses of 28 and 18 kDa (9 kDa in the presence of reducing agent). The intraperitoneal injection of Mo-CBP4 (3.5 and 10 mg/kg) into mice 30 min before acetic acid administration potently and significantly reduced the occurrence of abdominal writhing in a dose dependent manner by 44.7% and 100%, respectively. In addition, the oral administration of the protein (10 mg/kg) resulted in 18% and 52.8% reductions in abdominal writhing when given 30 and 60 min prior to acetic acid administration, respectively. Mo-CBP4, when administered by intraperitoneal route, also caused a significant and dose-dependent inhibition of peritoneal capillary permeability induced by acid acetic and significantly inhibited leukocyte accumulation in the peritoneal cavity. In conclusion, this pioneering study describes that the chitin-binding protein Mo-CBP4, from M. oleifera seeds, exhibits anti-inflammatory and antinociceptive properties and scientifically supports the use of this multipurpose tree in folk medicine.     

Anxiogenic and antinociceptive effects induced by corticotropin-releasing factor (CRF) injections into the periaqueductal gray are modulated by CRF1 receptor in mice

Chemical or electrical stimulation of the dorsal portion of the midbrain periaqueductal gray (dPAG) produces anxiogenic and antinociceptive effects. In rats, chemical stimulation of dPAG by local infusion of the neuropeptide corticotropin-releasing factor (CRF) provokes anxiogenic effects in the elevated plus-maze test (EPM). CRF also produces antinociception when injected intracerebroventricularly in rats, however it remains unclear whether this response is also observed following CRF injection into the dPAG in mice. Yet, given that there are CRF1 and CRF2 receptor subtypes within the PAG, it is important to show in which receptor subtypes CRF exert its anxiogenic and antinociceptive effects in the dPAG. Here, we investigated the role of these receptors in the anxiogenic (assessed in the EPM) and antinociceptive (assessed by the Formalin test: 2.5% formalin injection into the right hind paw) effects following intra-dPAG infusion of CRF in mice. The results show that intra-dPAG injections of CRF (75 pmol/0.1 μl and 150 pmol/0.2 μl) produced dose-dependent anxiogenic and antinociceptive effects. In addition, local infusion of NBI 27914 (5-chloro-4-(N-(cyclopropyl)methyl-N-propylamino)-2-methyl-6-(2,4,6-trichlorophenyl)-aminopyridine; 2 nmol/0.2 μl), a CRF1 receptor antagonist, completely blocked both the anxiogenic and antinociceptive effects induced by local infusion of CRF, while that of antisauvagine 30 (ASV30; 1 nmol/0.2 μl), a CRF2 receptor antagonist, did not alter the CRF effects. Present results are suggestive that CRF1 (but not CRF2) receptors play a crucial role in the anxiogenic and antinociceptive effects induced by CRF in the dPAG in mice.     

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

The relationship between autoimmunity and malaria is not well understood. To determine whether autoimmune responses have a protective role during malaria, we studied the pattern of reactivity to plasmodial antigens of sera from 93 patients with 14 different autoimmune diseases (AID) who were not previously exposed to malaria. Sera from patients with 13 different AID reacted against Plasmodium falciparum by indirect fluorescent antibody test with frequencies varying from 33-100%. In addition, sera from 37 AID patients were tested for reactivity against Plasmodium yoelii 17XNL and the asexual blood stage forms of three different P. falciparum strains. In general, the frequency of reactive sera was higher against young trophozoites than schizonts (p < 0.05 for 2 strains), indicating that the antigenic determinants targeted by the tested AID sera might be more highly expressed by the former stage. The ability of monoclonal auto-antibodies (auto-Ab) to inhibit P. falciparum growth in vitro was also tested. Thirteen of the 18 monoclonal auto-Ab tested (72%), but none of the control monoclonal antibodies, inhibited parasite growth, in some cases by greater than 40%. We conclude that autoimmune responses mediated by auto-Ab may present anti-plasmodial activity.     

Phylogeography and population history of the crab-eating fox (Cerdocyon thous)

The crab-eating fox is a medium-sized Neotropical canid with generalist habits and a broad distribution in South America. We have investigated its genetic diversity, population structure and demographic history across most of its geographic range by analysing 512 base pairs (bp) of the mitochondrial DNA (mtDNA) control region, 615 bp of the mtDNA cytochrome b gene and 1573 total nucleotides from three different nuclear fragments. MtDNA data revealed a strong phylogeographic partition between northeastern Brazil and other portions of the species' distribution, with complete separation between southern and northern components of the Atlantic Forest. We estimated that the two groups diverged from each other c. 400,000-600,000 years ago, and have had contrasting population histories. A recent demographic expansion was inferred for the southern group, while northern populations seem to have had a longer history of large population size. Nuclear sequence data did not support this north-south pattern of subdivision, likely due at least in part to secondary male-mediated historical gene flow, inferred from multilocus coalescent-based analyses. We have compared the inferred phylogeographic patterns to those observed for other Neotropical vertebrates, and report evidence for a major north-south demographic discontinuity that seems to have marked the history of the Atlantic Forest biota.     

Age-associated changes in gene expression in the anterior pituitary glands of female Japanese black cattle

Mammalian Genome - Proper functioning of the anterior pituitary (AP) gland is imperative, however, is suppressed by aging via unclear mechanisms. Therefore, we identified differentially expressed...     

Malaria in Brazil: what happens outside the Amazonian endemic region

Brazil, a country of continental proportions, presents three profiles of malaria transmission. The first and most important numerically, occurs inside the Amazon. The Amazon accounts for approximately 60% of the nation’s territory and approximately 13% of the Brazilian population. This region hosts 99.5% of the nation’s malaria cases, which are predominantly caused by Plasmodium vivax (i.e., 82% of cases in 2013). The second involves imported malaria, which corresponds to malaria cases acquired outside the region where the individuals live or the diagnosis was made. These cases are imported from endemic regions of Brazil (i.e., the Amazon) or from other countries in South and Central America, Africa and Asia. Imported malaria comprised 89% of the cases found outside the area of active transmission in Brazil in 2013. These cases highlight an important question with respect to both therapeutic and epidemiological issues because patients, especially those with falciparum malaria, arriving in a region where the health professionals may not have experience with the clinical manifestations of malaria and its diagnosis could suffer dramatic consequences associated with a potential delay in treatment. Additionally, because the Anopheles vectors exist in most of the country, even a single case of malaria, if not diagnosed and treated immediately, may result in introduced cases, causing outbreaks and even introducing or reintroducing the disease to a non-endemic, receptive region. Cases introduced outside the Amazon usually occur in areas in which malaria was formerly endemic and are transmitted by competent vectors belonging to the subgenus Nyssorhynchus (i.e., Anopheles darlingi, Anopheles aquasalis and species of the Albitarsis complex). The third type of transmission accounts for only 0.05% of all cases and is caused by autochthonous malaria in the Atlantic Forest, located primarily along the southeastern Atlantic Coast. They are caused by parasites that seem to be (or to be very close to) P. vivax and, in a less extent, by Plasmodium malariae and it is transmitted by the bromeliad mosquito Anopheles (Kerteszia) cruzii. This paper deals mainly with the two profiles of malaria found outside the Amazon: the imported and ensuing introduced cases and the autochthonous cases. We also provide an update regarding the situation in Brazil and the Brazilian endemic Amazon.     

Intraguild Predation and Interspecific Killing as Structuring Forces of Carnivoran Communities in South America

Intraguild predation (IGP) and interspecific killing (IK) have been recently acknowledged as important ecological forces that could influence community structure. Not only can carnivores influence prey community composition, they might also impact the populations of other carnivores. The goal of the current study was to assess the role of IGP and IK as significant forces influencing carnivoran assemblages in South America. To this end, we compiled the available records on 35 species of terrestrial carnivorans in the subcontinent, to investigate the potential and actual extent of IGP/IK as widespread ecological forces. We considered potential intraguild predators those having >20 % range overlap and body mass 2–5.4 times greater than that of other guild members and likely-potential intraguild predators those that, in addition, were also hypercarnivorous. The potential number of intraguild predators for those species evaluated ranged from zero to 18 (mean?=?5.35?±?SE 0.74). IGP/IK events (n?=?116) included 52 pairs of Neotropical carnivorans, 13 of which were killers and 25 were victims. Confirmed intraguild predator species (n?=?13) accounted for 37.1 % of the assemblage, nearly the same value predicted to be likely potential predators (n?=?14). IGP and IK were highly associated with the hypercarnivorous felids, whereas victim species were most often the omnivorous procyonids and skunks. The results indicate jaguars, pumas, and ocelots as the species most likely to have significant impact on the guild. IGP and IK are not random and reflect widespread interactions that influence carnivoran community structure in South America.     

Evaluation of the mutagenicity and antimutagenicity of Ziziphus joazeiro Mart. bark in the micronucleus assay

The aim of this study was to evaluate the mutagenicity (clastogenicity/aneugenicity) of a glycolic extract of Ziziphus joazeiro bark (GEZJ) by the micronucleus assay in mice bone marrow. Antimutagenic activity was also assessed using treatments associated with GEZJ and doxorubicin (DXR). Mice were evaluated 24–48 h after exposure to positive (N-nitroso-N-ethylurea, NEU - 50 mg.kg⁻¹ and DXR - 5 mg.kg⁻¹) and negative (150 mM NaCl) controls, as well as treatment with GEZJ (0.5–2 g.kg⁻¹), GEZJ (2 g.kg⁻¹) + NEU and GEZJ (2 g.kg⁻¹) + DXR. There were no significant differences in the frequencies of micronucleated polychromatic erythrocytes in mice treated with GEJZ and GEJZ + DXR compared to the negative controls, indicating that GEZJ was not mutagenic. Analysis of the polychromatic:normochromatic erythrocyte ratio revealed significant differences in the responses to doses of 0.5 g.kg⁻¹ and 1–2 g.kg⁻¹ and the positive control (NEU). These results indicated no systemic toxicity and moderate toxicity at lower and higher doses of GEZJ. The lack of mutagenicity and systemic toxicity in the antimutagenic assays, especially for treatment with GEZJ + DXR, suggested that phytochemical compounds in Z. joazeiro bark attenuated DXR-induced mutagenicity and the moderate systemic toxicity of a high dose of Z. joazeiro bark (2 g.kg⁻¹). Further studies on the genotoxicity of Z. joazeiro extracts are necessary to establish the possible health risk in humans and to determine the potential as a chemopreventive agent for therapeutic use.