Use of Isobutyl Nitrite as a Recreational Drug

Information on the use of isobutyl nitrite as a recreational drug and on its side effects was obtained from conversations with 150 users.     

Primary production: Depression of oxygen evolution in algal cultures by organophosphorus insecticides

Bulletin of Environmental Contamination and Toxicology - Photosynthesis of four estuarine phytoplankters was inhibited by Baytex and Abate (organophosphates), Baygon (carbamate) and DDT...     

Interleukin-12 induces a Th1-like response to Burkholderia mallei and limited protection in BALB/c mice

We evaluated the effect of interleukin (IL)-12 on the immune response to Burkholderia mallei in BALB/c mice. Mice were vaccinated with non-viable B. mallei cells with or without IL-12. There was a seven- to nine-fold increase in IgG2a levels, and a significant increase in the proliferative response and interferon (IFN)-gamma production by splenocytes from mice that received B. mallei and IL-12. We saw an increase in survivors in the groups of mice that received B. mallei and IL-12 when challenged, compared to mice that received only B. mallei or IL-12. The results suggest that IL-12 can enhance the Th1-like immune response to B. mallei and mediate limited protection from a lethal challenge.     

Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat

Citicoline and lithium (Li(-)) have been shown to support retinal ganglion cell (RGC) survival and axon regeneration in vitro. Optic nerve crush (ONC) is a model of both brain axonal injury and certain aspects of the glaucomatous degeneration of RGC. We have used this model to quantify protection offered to RGC by these drugs and to determine whether their effects are mediated by enhanced expression of the antiapoptotic protein Bcl-2. Adult rats (6-12 per group) were subjected to ONC accompanied by a contralateral sham operation. Animals were treated intraperitoneally with either vehicle, citicoline sodium (1g/kg daily for up to 7 days and 300 mg/kg daily afterwards), lithium chloride (30 mg/kg daily), or both drugs combined. Fluorogold was injected bilaterally into superior colliculi 1, 5 or 19 days after ONC. Labeled cells were counted under a fluorescence microscope 2 days after tracer injection. In a separate set of experiments the effects of treatments on expression of Bcl-2 in retinas were evaluated by immunohistochemistry. In vehicle-treated animals there was a progressive decrease of RGC density after crush. This decrease was attenuated in citicoline-treated animals 1 week and 3 weeks after the crush. In the lithium-treated group protection was even more pronounced. In animals treated with both drugs RGC protection was similar to that achieved by lithium alone. Bcl-2 immunoreactivity was seen predominantly in retinal ganglion cells. Its increase was recorded in the lithium and citicoline group as well as in animals treated with the combination of both drugs. Both citicoline and lithium protect RGC and their axons in vivo against delayed degeneration triggered by the ONC. Retinoprotective action of both drugs may involve an increase in Bcl-2 expression.     

Retinal and ciliary body pigment epithelium suppress activation of T lymphocytes via transforming growth factor beta

The ocular microenvironment is immunosuppressive and anti-inflammatory. Pigment epithelial (PE) cells isolated from the eye possess a new property of suppressing T cell receptor-dependent activation of T cells in vitro. This property depends on their capacity to produce cell-surface and soluble inhibitory molecules. The iris pigment epithelia (IPE) do so through direct cell-to-cell contact with na?ve T cells, and this suppressive contact is mediated by interactions between B7 and membrane-bound TGFbeta that are expressed constitutively on IPE. We have now examined whether other ocular PE cells, e.g., retinal pigment epithelia (RPE) and ciliary body pigment epithelia (CBPE), have a similar suppressive property by a similar process. We have found that RPE and CBPE significantly suppress the activation of bystander T cells via soluble inhibitory factors. RPE and CBPE secrete different soluble inhibitory factors including TGFbeta1 and TGFbeta2. Although IPE cells suppress the activation of bystander T cells by membrane-bound TGFbeta, the RPE and CBPE do so by soluble forms of active TGFbeta through mechanisms independent of cell contact. These ocular PE cells are capable modifying T cell function by enhancing production of regulatory cytokines including TGFbeta. We propose that this mechanism of suppression via TGFbeta ensures that soluble active TGFbeta is released into the ocular microenvironment in order to create the immune privilege of the posterior segment of the eye.     

Tumor cell lines expressing the proteasome subunit isoform LMP7E1 exhibit immunoproteasome deficiency

The immune system can recognize antigenic peptides derived from tumors by their presentation on MHC class I complexes to CTLs. Immunoproteasomes (i20S) can substantially enhance the MHC class I peptide repertoire, making down-regulation of i20S an important strategy of tumor cells in manipulating immune surveillance. Here, we report that human cancer cells express the nonfunctional immunosubunit-variant LMP7E1, in addition to, or instead of LMP7E2, in response to IFN-gamma. This preferential expression of LMP7E1 and the consequent down-regulation of LMP7E2 results in i20S deficiency. The molecular explanation for this phenomenon is the incapacity of LMP7E1 to interact efficiently with the proteasome maturation protein, which regularly recruits LMP7E2 into nascent i20S precursor complexes. In contrast to previous reports, i20S formation in these cancer cells cannot be restored by IFN-gamma treatment. However, expression of LMP7E2 in these cells restores the i20S-deficient phenotype. Thus, our data describe a novel mechanism that contributes to the process of oncogenesis.     

Antioxidant status of pair-fed labrador retrievers is affected by diet restriction and aging

Twenty-four sibling pairs of 8-wk-old Labrador Retrievers were assigned to an experiment to determine the effects of diet restriction (75% of control-fed pair mate) on the quality and span of canine life and to identify biological markers of aging in dogs. The antioxidant status of these dogs was monitored by annual assays for serum retinol (RT), retinyl palmitate (RP), total vitamin A (VA), vitamin E (VE), selenium (Se), copper (Cu), and ceruloplasmin (Cp), plasma ascorbic acid (AA), uric acid (UA), and total peroxyl-radical trapping activity (TRAP), and whole-blood glutathione peroxidase (Gpx). Data in this report are for the 6-y period of the experiment when the dogs were between 5 and 10 y of age. Diet restriction reduced RT, VE, Cu, and Cp. Aging was associated with decreased RP, VA, VE, Se, and Cu and with increased RT, Cp, and Gpx. Female dogs had lower RP, VA, Cu, and Cp than male dogs. Litter effects were observed for VE, Cu, UA, and Gpx. Treatment effects on serum RT and Cu suggest that these variables are not as regulated homeostatically by hepatic storage as in most other species. Although the antioxidant profiles did not elucidate how diet restriction contributes to longevity, they have the potential to enhance our understanding of canine clinical nutrition and to have practical applications in formulating canine diets.