Tolerance to chronic delta-9-tetrahydrocannabinol (Δ?-THC) in rhesus macaques infected with simian immunodeficiency virus.

Although Δ?-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ?-THC before and after inoculation with simian immunodeficiency virus (SIVmac251, 100 TCID??/ml, i.v.). Prior to chronic Δ?-THC and SIV inoculation, 0.032–0.32 mg/kg of Δ?-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ?-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/?SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ?-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ?-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Fermentative hydrogen production with xylose by Clostridium and Klebsiella species in anaerobic batch reactors

Hydrogen production was obtained from low concentrations of xylose metabolized by heat treated inoculum obtained from the slaughterhouse wastewater treatment UASB reactor installed in Brazil. The molecular biological analysis Clostridium and Klebsiella species, recognized as H₂ and volatile acid producers, in addition to Burkholderia species and uncultivated bacteria. The assays were carried out in batch reactors: (1) 630.0 mg xylose/L, (2) 1341.0 mg xylose/L, (3) 1848.0 mg xylose/L and (4) 3588.0 mg xylose/L. The following yields were obtained: 3% (0.2 mol H₂/mol xylose), 8% (0.5 mol H₂/mol xylose), 10% (0.6 mol H₂/mol xylose) and 14% (0.8 mol H₂/mol xylose), respectively. The end products obtained were acetic acid, butyric acid, methanol and ethanol in all of the anaerobic reactors. The concentrations of xylose did not inhibit microbial growth and hydrogen production. This suggested that low concentrations of xylose should be added to wastewater to produce hydrogen.     

Structure–Activity Relationships and Binding Mode in the Human Acetylcholinesterase Active Site of Pseudo‐Irreversible Inhibitors Related to Xanthostigmine

Acetylcholinesterase inhibitors : We extended the AChE inhibitors SAR study to newly synthesized compounds based on the lead compound xantostigmine. Docking and molecular dynamics simulations were carried out to both define a new computational protocol, and to acquire a better understanding of the SAR data. These computations prompted us to evaluate two of the synthesized compounds as inhibitors of AChE‐induced Aβ aggregation.

     

Evaluation of Friction Behavior and Its Contact-Area Dependence at the Micro- and Nano-Scales

The friction behavior of two different materials, mica and ultra-high molecular weight polyethylene (UHMWPE), was evaluated at the nanoscale with an atomic force microscope and with a custom-built ball-on-flat microtribometer at the microscale. The same counterface (Si₃N₄ probe), environmental conditions (25 °C, RH < 10%), and similar load ranges were maintained for all experiments. The friction-force data obtained were analyzed for contact-area dependence. Friction force between silicon nitride and mica at the nanoscale showed initial non-linearity with normal load up to a certain load, beyond which surface damage was observed resulting in a linear dependence of friction force on normal load. At the microscale, the friction force of the mica–silicon nitride interface exhibited linear dependence on normal load. Friction force between silicon nitride and UHMWPE exhibited non-linearity with normal load at both the length scales, for the applied load ranges of our experiment. An appropriate contact mechanics theory was applied to calculate an interfacial shear strength value for the material pair at both the scales. The values at both the scales were similar, when the conditions were carefully maintained to be the same across scales.     

CFH Loss in Human RPE Cells Leads to Inflammation and Complement System Dysregulation via the NF-κB Pathway

Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is a degenerative disease of the macula, where retinal pigment epithelium (RPE) cells are damaged in the early stages of the disease, and chronic inflammatory processes may be involved. Besides aging and lifestyle factors as drivers of AMD, a strong genetic association to AMD is found in genes of the complement system, with a single polymorphism in the complement factor H gene (CFH), accounting for the majority of AMD risk. However, the exact mechanism of CFH dysregulation confers such a great risk for AMD and its role in RPE cell homeostasis is unclear. To explore the role of endogenous CFH locally in RPE cells, we silenced CFH in human hTERT-RPE1 cells. We demonstrate that endogenously expressed CFH in RPE cells modulates inflammatory cytokine production and complement regulation, independent of external complement sources, or stressors. We show that loss of the factor H protein (FH) results in increased levels of inflammatory mediators (e.g., IL-6, IL-8, GM-CSF) and altered levels of complement proteins (e.g., C3, CFB upregulation, and C5 downregulation) that are known to play a role in AMD. Moreover, our results identify the NF-κB pathway as the major pathway involved in regulating these inflammatory and complement factors. Our findings suggest that in RPE cells, FH and the NF-κB pathway work in synergy to maintain inflammatory and complement balance, and in case either one of them is dysregulated, the RPE microenvironment changes towards a proinflammatory AMD-like phenotype.     

Th17-Related Cytokines as Potential Discriminatory Markers between Neuromyelitis Optica (Devic’s Disease) and Multiple Sclerosis—A Review

Multiple sclerosis (MS) and Devic’s disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.     

Starve to Sustain—An Ancient Syrian Landrace of Sorghum as Tool for Phosphorous Bio-Economy?

Phosphorus (P) is an essential macronutrient, playing a role in developmental and metabolic processes in plants. To understand the local and systemic responses of sorghum to inorganic phosphorus (P_i) starvation and the potential of straw and ash for reutilisation in agriculture, we compared two grain (Razinieh) and sweet (Della) sorghum varieties with respect to their morpho-physiological and molecular responses. We found that P_i starvation increased the elongation of primary roots, the formation of lateral roots, and the accumulation of anthocyanin. In Razinieh, lateral roots were promoted to a higher extent, correlated with a higher expression of SbPht1 phosphate transporters. Infrared spectra of straw from mature plants raised to maturity showed two prominent bands at 1371 and 2337 cm⁻¹, which could be assigned to P-H(H₂) stretching vibration in phosphine acid and phosphinothious acid, and their derivates, whose abundance correlated with phosphate uptake of the source plant and genotype (with a higher intensity in Razinieh). The ash generated from these straws stimulated the shoot elongation and root development of the rice seedlings, especially for the material derived from Razinieh raised under P_i starvation. In conclusion, sorghum growing on marginal lands has potential as a bio-economy alternative for mineral phosphorus recycling.