Inhibition of nitric oxide synthase isoforms by porphyrins.

Protoporphyrin IX inhibits citrulline formation by all three nitric oxide synthase isoforms in a manner reversible by dilution. Zinc protoporphyrin IX, by contrast, produces a time- and concentration-dependent inactivation of all three nitric oxide synthase isoforms, not reversible by dilution. The inhibition of citrulline formation by protoporphyrin IX occurs with IC50 values of 0.8, 4, and 5 microM for the nNOS, iNOS, and eNOS isoforms, respectively. Inhibition by N-methyl-protoporphyrin IX occurs at IC50 values of 6, 5, and 8 microM for the nNOS, iNOS, and eNOS isoforms, respectively. Inhibition of nitric oxide synthase by protoporphyrin IX is a multisite, positively cooperative inhibition that exhibits a Hill coefficient of 2.3 for the iNOS isoform. Protoporphyrin IX reduces the maximal velocity of citrulline formation for both the iNOS and nNOS isoforms without altering the K(m) for the arginine substrate or the EC50 value for the tetrahydrobiopterin cofactor. Protoporphyrin IX inhibits the arginine-independent NADPH oxidase activity of nNOS with an IC50 value of 1 microM but has no effect on cytochrome c reductase activity at concentrations as high as 30 microM. At concentrations of 10 and 20 microM, protoporphyrin IX inhibits NO formation by cytokine-induced murine RAW 264.7 cells; however, these inhibitions are accompanied by significant cellular cytotoxicity. Coproporphyrins I and III, uroporphyrins I and III, and porphobilinogen, intermediates in the biosynthesis of heme that accumulate in hepatic porphyrias, are ineffective as inhibitors of the nitric oxide synthase isoforms. Since protoporphyrin IX is the immediate biosynthetic precursor of heme that accumulates in hepatic protoporphyria, iron deficiency anemia, and lead poisoning, protoporphyrin IX inhibition of nitric oxide synthase may contribute to the pathophysiology of these conditions.

Prevention of posterior capsular opacification by cryolysis and the use of heparinized irrigating solution during extracapsular lens extraction in rabbits.

We tried applying a specially-designed cryoprobe to the posterior capsule as well as adding heparin, an anticoagulative, anti-inflammatory compound, to the anterior chamber irrigation solution in an attempt to inhibit secondary cataract formation following a planned extracapsular lens extraction in 36 rabbits. The first group received both cryo treatment and heparin; a second group received heparin without cryo treatment; a third group received neither heparin nor cryo treatment. Complete opacification of the lens developed 3 months after the operation in all the rabbits not treated with heparin, and in 50% of those that received heparin. The addition of cryo treatment to the heparin-treated rabbits further reduced opacification by 20%. We conclude that in rabbits, cryo treatment, combined with intracameral administration of heparin during surgery, has a significant inhibitory effect on secondary cataract formation.

Epithelial cyst in cerebellopontine angle with xanthogranulomatous changes simulating cholesterol granuloma.

We describe the clinical, radiological, and pathological features of an epithelial lined cyst in the cerebellopontine angle of a 54-year-old man who presented with headaches, ataxia, and multiple cranial nerve dysfunction. The surgically excised lesion showed a cyst lined by ciliated columnar epithelium with copious mucin secretion similar to that seen in colloid cysts of the third ventricle and enterogenous cysts of the spinal canal. In addition the cyst contained brownish material with an exuberant xanthogranulomatous reaction and numerous cholesterol clefts. This lesion closely resembled a cholesterol granuloma by radiographic and pathologic studies. Although two examples of neuroepithelial lined cysts have been described in the cerebellopontine angle, to our knowledge a lesion similar to that in our patient has not been reported previously.

Diffuse pulmonary ossification detected by bone scanning with Tc-99m hydroxymethylene diphosphate.

Diffuse pulmonary ossification (DPO) is a rare pathologic finding of heterotropic bone formation within the lungs. It has been associated with mitral stenosis, chronic left ventricular failure, interstitial fibrosis, metastatic breast cancer, pulmonary amyloidosis, histoplasmosis, and chronic busulfan therapy. This patient represents a case associated with Placidyl use.