Granulomas that consist of focal accumulations of macrophages are commonly found in the liver due to stimulation of the immune system by a number of agents. Manifestations are variable depending on whether the underlying cause is a systemic disease or a primary hepatic granulomatous reaction. This article describes the common causes, presentation, histopathology, and manifestations of granulomatous diseases as well as various diagnostic and management strategies.

1 Vasorelaxation to b 2 -adrenoceptor stimulation occurs through both endothelium-dependent and endothelium-independent mechanisms, and the former is mediated through Ca 2 þ -independent activation of endothelial-type nitric oxide synthase (NOS-3). Since Ca 2 þ -independent NOS-3 activation may occur through its serine phosphorylation via protein kinase A (PKA) or Akt, we determined the PKA and Akt dependency of b 2 -adrenergic relaxation of rat aorta. 2 Rat aortic rings were pre-incubated with the PKA inhibitor H-89 (10 À7 M), the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (5 Â 10 À7 M), Akt inhibitor (10 À5 M), or vehicle, in the absence or presence of the NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME, 10 À4 M). Rings were then contracted with phenylephrine (10 À7 M), and concentration-relaxation responses determined to the b 2 -adrenoceptor agonist albuterol. 3 Rings exhibited a concentration-dependent relaxation to albuterol: pEC 50 6.970.2, E max 88.274.0%. L-NAME attenuated E max to 60.273.5% (Po0.001). 4 In the presence of L-NAME, wortmannin or Akt inhibitor did not influence albuterol responses, whereas H-89 reduced E max further, to 27.572.2% (Po0.001). 5 In the absence of L-NAME, E max to albuterol was reduced by H-89, wortmannin or Akt inhibitor, to 56.272.2, 56.071.6 and 55.471.8%, respectively (Po0.001 for each); the combinations H-89 plus wortmannin or H-89 plus Akt inhibitor reduced E max further still. 6 Western blotting of NOS-3 immunoprecipitates from rat aortas confirmed that albuterol increased serine phosphorylation of NOS-3, and this increase was attenuated by H-89 or Akt inhibitor. 7 Our results indicate that b 2 -adrenoceptor stimulation relaxes rat aorta through both NOdependent and independent mechanisms. The latter is predominantly PKA-mediated, whereas the former occurs through both PKA and PI3K/Akt activation.

Mitochondria are the proximate target of a number of different neurotoxins. Typically, impairing of the key bioenergetic function of mitochondria by toxins is considered as the main mechanism of action. However, the effective maintenance of energy generation in neurons depends on the biogenesis, trafficking, and degradation of mitochondria in addition to the traditional bioenergetic functions. We have recently demonstrated that glutamate alters both the trafficking and morphology of mitochondria in primary neurons. In addition, several other potential neurotoxins, including nitric oxide and zinc, inhibit mitochondrial movement and, in some cases, alter morphology too. This suggests that some part of the action of neurotoxins might include the impairment of mitochondrial trafficking in neurons, with the resultant failure of local ATP delivery.

No abstract

No abstract