Acute Ethanol Effects on Focal Cerebral Ischemia in Nonfasted Rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66417/1/j.1530-0277.1997.tb03832.x.pd

CD36 deficiency attenuates experimental mycobacterial infection

<p>Abstract</p> <p>Background</p> <p>Members of the CD36 scavenger receptor family have been implicated as sensors of microbial products that mediate phagocytosis and inflammation in response to a broad range of pathogens. We investigated the role of CD36 in host response to mycobacterial infection.</p> <p>Methods</p> <p>Experimental <it>Mycobacterium bovis </it>Bacillus Calmette-Guérin (BCG) infection in <it>Cd36^+/+</it>and <it>Cd36^-/-</it>mice, and <it>in vitro </it>co-cultivation of <it>M. tuberculosis</it>, BCG and <it>M. marinum </it>with <it>Cd36^+/+</it>and <it>Cd36^-/-</it>murine macrophages.</p> <p>Results</p> <p>Using an <it>in vivo </it>model of BCG infection in <it>Cd36^+/+</it>and <it>Cd36^-/-</it>mice, we found that mycobacterial burden in liver and spleen is reduced (83% lower peak splenic colony forming units, p < 0.001), as well as the density of granulomas, and circulating tumor necrosis factor (TNF) levels in <it>Cd36^-/-</it>animals. Intracellular growth of all three mycobacterial species was reduced in <it>Cd36^-/-</it>relative to wild type <it>Cd36^+/+</it>macrophages <it>in vitro</it>. This difference was not attributable to alterations in mycobacterial uptake, macrophage viability, rate of macrophage apoptosis, production of reactive oxygen and/or nitrogen species, TNF or interleukin-10. Using an <it>in vitro </it>model designed to recapitulate cellular events implicated in mycobacterial infection and dissemination <it>in vivo </it>(i.e., phagocytosis of apoptotic macrophages containing mycobacteria), we demonstrated reduced recovery of viable mycobacteria within <it>Cd36^-/-</it>macrophages.</p> <p>Conclusions</p> <p>Together, these data indicate that CD36 deficiency confers resistance to mycobacterial infection. This observation is best explained by reduced intracellular survival of mycobacteria in the <it>Cd36^-/-</it>macrophage and a role for CD36 in the cellular events involved in granuloma formation that promote early bacterial expansion and dissemination.</p

Cell-Intrinsic NF-κB Activation Is Critical for the Development of Natural Regulatory T Cells in Mice

regulatory T (Treg) cells develop in the thymus and represent a mature T cell subpopulation critically involved in maintaining peripheral tolerance. The differentiation of Treg cells in the thymus requires T cell receptor (TCR)/CD28 stimulation along with cytokine-promoted Foxp3 induction. TCR-mediated nuclear factor kappa B (NF-κB) activation seems to be involved in differentiation of Treg cells because deletion of components of the NF-κB signaling pathway, as well as of NF-κB transcription factors, leads to markedly decreased Treg cell numbers in thymus and periphery. thymic Treg precursors and their further differentiation into mature Treg cells. Treg cell development could neither be completely rescued by the addition of exogenous Interleukin 2 (IL-2) nor by the presence of wild-type derived cells in adoptive transfer experiments. However, peripheral NF-κB activation appears to be required for IL-2 production by conventional T cells, thereby participating in Treg cell homeostasis. Moreover, pharmacological NF-κB inhibition via the IκB kinase β (IKKβ) inhibitor AS602868 led to markedly diminished thymic and peripheral Treg cell frequencies.Our results indicate that Treg cell-intrinsic NF-κB activation is essential for thymic Treg cell differentiation, and further suggest pharmacological NF-κB inhibition as a potential therapeutic approach for manipulating this process

Intensive insulin therapy versus conventional glycemic control in patients with acute neurological injury: a prospective controlled trial Insulinoterapia intensiva versus controle glicêmico em pacientes com injuria neurológica aguda: estudo prospectivo randomizado

OBJECTIVE: To compare intensive insulin therapy to conventional glycemic control in patients with acute neurological injury evaluating neurological outcome and morbimortality. METHOD: Patients with two glycemias above 150 mg/dL 12 hours after admission were randomized to receive intensive insulin therapy (G1) or conventional treatment (G2). We evaluated a subgroup of patients with acute brain injury from July, 2004 to June, 2006. RESULTS: G1 patients (n=31) received 70.5 (45.1-87.5) units of insulin/day while G2 patients (n=19) received 2 (0.6-14.1) units/day (p<0.0001). The median glycemia was comparable in both groups (p=0.16). Hypoglycemia occurred in 2 patients (6.4%) in G1 and in 1 patient (5.8%) in G2 (p=1.0). Mortality in G1 was of 25.8% and of 35.2% in G2 (relative reduction of 27%). Neurological outcome was similar in both groups. CONCLUSION: A less strict intensive insulin therapy can reduce hypoglycemia and still maintain its benefits.<br>OBJETIVO: Comparar insulinoterapia intensiva com controle convencional da glicemia em pacientes com injuria cerebral aguda avaliando evolução neurológica e morbimortalidade. MÉTODO: Pacientes com duas glicemias acima de 150 mg/dL nas primeiras 12 horas após admissão foram randomizados para insulinoterapia intensiva (Grupo 1) ou tratamento convencional (Grupo 2). Avaliamos um subgrupo de pacientes com injuria cerebral aguda admitidos de julho/2004 a junho/2006. RESULTADOS: O Grupo 1 (n=31) recebeu 70,5 (45,1-87,5) unidades de insulina/dia enquanto o Grupo 2 (n=19) recebeu 2 (0,6-14,1) unidades/dia (p<0,0001). A glicemia mediana foi comparável nos dois grupos (p=0,16). Hipoglicemia ocorreu em 2 pacientes (6,4%) no Grupo 1 e em 1 paciente (5,8%) no Grupo 2. A mortalidade no Grupo 1 foi 25,8% contra 35,2% no Grupo 2 (redução relativa de 27%). A evolução neurológica foi semelhante nos dois grupos. CONCLUSÃO: Insulinoterapia intensiva com controle mais flexível da glicemia reduz a incidência de hipoglicemia mantendo os benefícios do tratamento