The concomitant use of cannabis and cocaine coexists with increased LPS levels and systemic inflammation in male drug users.

Illicit drug use can cause a variety of effects including alterations in the immune system. The aim of this study was to investigate the effects of illicit drugs on circulating lipopolysaccharide (LPS), systemic inflammation and oxidative stress markers in drug users. We evaluated the levels of soluble CD14 (sCD14), LPS, inflammatory (TNF-α and IL-6) and regulatory (IL-10) cytokines, as well as C-reactive protein (CRP), lipid peroxidation (TBARS) and total thiols in the peripheral blood of 81 men included in groups of cannabis (n = 21), cocaine (n = 12), cannabis-plus-cocaine users (n = 27), and non-drug users (n = 21). The use of cannabis plus cocaine leads to higher systemic levels of LPS, CRP, IL-6 and higher IL-6/IL-10 ratio, characterizing a proinflammatory profile. In contrast, a regulatory profile as viewed by lower systemic TNF-α and IL-6 levels and lower TNF-α/IL-10 ratio were observed in cannabis users compared to the control group. Moreover, cocaine users presented a lower content of non-enzymatic antioxidant thiol compared to control group, cannabis group and cannabis plus cocaine group. In conclusion, our results indicate that the use of cannabis contributes to an anti-inflammatory/or regulatory profile while the concomitant cannabis plus cocaine consumption coexists with increased circulating amounts of LPS and proinflammatory status.

Distinct inflammatory profiles in HIV-infected individuals under antiretroviral therapy using cannabis, cocaine or cannabis plus cocaine.

OBJECTIVES: To evaluate the effects of cannabis and/or cocaine use on inflammatory, oxidative stress status and circulating monocyte subsets in HIV-infected individuals under antiretroviral therapy. DESIGN: Soluble CD14 (sCD14), intestinal fatty acid-binding protein (IFABP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and oxidative stress markers were examined. The monocyte subsets and their activation and cytokine production by peripheral blood mononuclear cells (PBMCs) of HIV-1 infected individuals upon lipopolysaccharide (LPS)-stimulation were also investigated. METHODS: sCD14, IFABP, TNF-α, IL-6, IL-8 and IL-10 levels were evaluated using ELISA, CRP by turbidimetry; lipid peroxidation (TBARS) spectrofluometrically and total thiol levels by using 5-5'-dithio-bis (2-nitrobenzoic acid) reagent. Monocyte subsets and activation were assessed by flow cytometry. RESULTS: All HIV-infected drug user groups showed higher sCD14 levels compared with HIV+ nondrug users. IFABP was increased in HIV+ drug-users in relation to healthy individuals. Cannabis use lowered the percentages of inflammatory, nonclassical, activated-classic and activated-inflammatory monocytes. Cocaine users showed increased plasmatic TNF-α and TBARS levels, decreased thiols content and lower activated-classic and inflammatory-monocyte percentages. Cannabis-plus-cocaine use increased CRP, IL-8 and IL-6/IL-10 ratio, but decreased thiol content, and inflammatory and activated-classic monocyte percentages. PBMCs of cannabis and cannabis-plus-cocaine users showed low-potential cytokine production either spontaneously or under LPS-stimulation. CONCLUSION: In HIV infection, the use of cannabis induces predominantly an anti-inflammatory profile. The use of cocaine and cannabis-plus-cocaine showed a mixed pro-inflammatory and anti-inflammatory profile, with predominance of inflammatory status. Further studies are required to better understand the action of these drugs in HIV infection.

Genome-wide association analysis of stalk biomass and anatomical traits in maize.

BACKGROUND: Maize stover is an important source of crop residues and a promising sustainable energy source in the United States. Stalk is the main component of stover, representing about half of stover dry weight. Characterization of genetic determinants of stalk traits provide a foundation to optimize maize stover as a biofuel feedstock. We investigated maize natural genetic variation in genome-wide association studies (GWAS) to detect candidate genes associated with traits related to stalk biomass (stalk diameter and plant height) and stalk anatomy (rind thickness, vascular bundle density and area). RESULTS: Using a panel of 942 diverse inbred lines, 899,784 RNA-Seq derived single nucleotide polymorphism (SNP) markers were identified. Stalk traits were measured on 800 members of the panel in replicated field trials across years. GWAS revealed 16 candidate genes associated with four stalk traits. Most of the detected candidate genes were involved in fundamental cellular functions, such as regulation of gene expression and cell cycle progression. Two of the regulatory genes (Zmm22 and an ortholog of Fpa) that were associated with plant height were previously shown to be involved in regulating the vegetative to floral transition. The association of Zmm22 with plant height was confirmed using a transgenic approach. Transgenic lines with increased expression of Zmm22 showed a significant decrease in plant height as well as tassel branch number, indicating a pleiotropic effect of Zmm22. CONCLUSION: Substantial heritable variation was observed in the association panel for stalk traits, indicating a large potential for improving useful stalk traits in breeding programs. Genome-wide association analyses detected several candidate genes associated with multiple traits, suggesting common regulatory elements underlie various stalk traits. Results of this study provide insights into the genetic control of maize stalk anatomy and biomass.

Crotalus durissus collilineatus Venom Induces TNF- α and IL-10 Production in Human Peripheral Blood Mononuclear Cells.

Snake venom has been the subject of numerous studies in an attempt to find properties and biological effects that may be beneficial to man. In this study we evaluated in vitro the effects of Crotalus durissus terrificus (Cdt) and Crotalus durissus collilineatus (Cdc) venom in human peripheral blood mononuclear cells (PBMCs). At 24 h, a significant decrease of viable cells was observed in cells stimulated with the Cdc venom at 0.0005 mg/mL and 0.005 mg/mL compared to the negative control. At 48 h, a significant decrease of viable cells was observed only in cells stimulated with Cdc venom at 0.005 mg/mL. A significant increase of TNF- α and IL-10 was detected 48 hours after culture of PBMC with Cdc, but not with Cdt venom. The expression of CD69 and PD1 (programmed death-1), activation and regulatory cell markers, on CD8+ and CD8- T cells did not change in the presence of Cdt and Cdc venom. Our results suggest the presence of proinflammatory and anti-inflammatory components in the Cdc venom. Further analysis should be done to identify those Cdc venom components as it has been done for the Cdt venom by other authors, indicating that modulatory components are found in the venom of different species of Crotalus snakes.

Inheritance of nitrogen use efficiency in inbred progenies of tropical maize based on multivariate diallel analysis.

The objective of our study was to characterize and determine the patterns of genetic control in relation to tolerance and efficiency of nitrogen use by means of a complete diallel cross involving contrasting inbred progenies of tropical maize based on a univariate approach within the perspective of a multivariate mixed model. Eleven progenies, previously classified regarding the tolerance and responsiveness to nitrogen, were crossed in a complete diallel cross. Fifty-five hybrids were obtained. The hybrids and the progenies were evaluated at two different nitrogen levels, in two locations. The grain yield was measured as well as its yield components. The heritability values between the higher and lower nitrogen input environment did not differ among themselves. It was observed that the general combining ability values were similar for both approaches univariate and multivariate, when it was analyzed within each location and nitrogen level. The estimate of variance of the specific combining ability was higher than general combining ability estimate and the ratio between them was 0.54. The univariate and multivariate approaches are equivalent in experiments with good precision and high heritability. The nonadditive genetic effects exhibit greater quantities than the additive genetic effects for the genetic control of nitrogen use efficiency.