We determined the effects of cyclooxygenase-1 (COX-1; SC-560), COX-2 (SC-58125), and inducible nitric oxide synthase (iNOS; 1400W) inhibitors on atorvastatin (ATV)-induced myocardial protection and whether iNOS mediates the ATV-induced increases in COX-2. Sprague-Dawley rats received 10 mg ATV.kg(-1).day(-1) added to drinking water or water alone for 3 days and received intravenous SC-58125, SC-560, 1400W, or vehicle alone. Anesthesia was induced with ketamine and xylazine and maintained with isoflurane. Fifteen minutes after intravenous injection rats underwent 30-min myocardial ischemia followed by 4-h reperfusion [infarct size (IS) protocol], or the hearts were explanted for biochemical analysis and immunoblotting. Left ventricular weight and area at risk (AR) were comparable among groups. ATV reduced IS to 12.7% (SD 3.1) of AR, a reduction of 64% vs. 35.1% (SD 7.6) in the sham-treated group (P < 0.001). SC-58125 and 1400W attenuated the protective effect without affecting IS in the non-ATV-treated rats. ATV increased calcium-independent NOS (iNOS) [11.9 (SD 0.8) vs. 3.9 (SD 0.1) x 1,000 counts/min; P < 0.001] and COX-2 [46.7 (SD 1.1) vs. 6.5 (SD 1.4) pg/ml of 6-keto-PGF(1alpha); P < 0.001] activity. Both SC-58125 and 1400W attenuated this increase. SC-58125 did not affect iNOS activity, whereas 1400W blocked iNOS activity. COX-2 was S-nitrosylated in ATV-treated but not sham-treated rats or rats pretreated with 1400W. COX-2 immunoprecipitated with iNOS but not with endothelial nitric oxide synthase. We conclude that ATV reduced IS by increasing the activity of iNOS and COX-2, iNOS is upstream to COX-2, and iNOS activates COX-2 by S-nitrosylation. These results are consistent with the hypothesis that preconditioning effects are mediated via PG.

Background-Both statins and thiazolidinediones have antiinflammatory properties. However, the exact mechanisms underlying these effects are unknown. We investigated whether atorvastatin (ATV) and pioglitazone (PIO) increase the myocardial content of lipoxin-A 4 and 15(R)-epi-lipoxin-A 4 (15-epi-LXA 4 ), both arachidonic acid products with strong antiinflammatory properties. Methods and Results-In experiment 1, rats received 3-day pretreatment with water; PIO 2, 5, or 10 mg · kg Ϫ1 · d Ϫ1 ; ATV 2, 5, or 10 mg · kg Ϫ1 · d

expensive agents. Intravenous and subcutaneous drugs followed different trends. For instance, observed costs of infliximab fell under the expected range without market entries.Using TNF inhibitors as a case study, we showed that increased competition in the pharmaceutical market does not necessarily translate into price reductions. Our findings illustrate a market failure contributing to the rising costs of prescription drugs.

Utilization of PR during the study period increased only 1.1% in these Medicare beneficiaries with COPD and remained low.

Nodular fasciitis is a benign reactive myofibroblastic proliferative process of unknown etiology. It presents as a solitary painless, rapidly growing nodule over several weeks' duration. The condition is self-limited, and proper diagnosis is essential to avoid unnecessary aggressive treatment. Diagnosis is often a challenge because it may be confused with a malignant tumor due to its aggressive clinical behavior and histological features. Immunohistochemical staining can be a useful tool to aid in the diagnosis. Although most commonly located on the extremities and then the trunk, it is estimated that the head and neck region represents only 10 to 20%. The majority of cases arise in the soft tissue, i.e. fascia, muscle, or subcutaneous tissue. Interestingly, cases in the head and neck region often involve dermal tissue. There have been five separate reports documenting rare cases of dermal nodular fasciitis in the dermatopathology literature and one case series involving 28 of 50 dermal variants from the external ear region. We report three additional cases of dermal nodular fasciitis occurring on the left cheek, base of the scalp, and right medial canthus.