IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Treatment of acne vulgaris. Guidelines for primary care physicians.

The spectrum of acne vulgaris is wide, ranging from minor comedones to devastating nodules and cysts. Appropriate therapy requires an understanding of the various types of lesions, their pathophysiology, and the rationale for treatment. Good patient rapport and communication are important, and close follow-up is necessary until the treatment regimen has stabilized. Timely referral to a dermatologist is essential when therapy is not effective. With effort, the treatment of acne can be quite rewarding for both patient and physician.     

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation

We investigated the degree and time course of neutrophil sequestration into human lungs during cardiac operations. At the same time, measurement of the concentration of peroxidation products in the plasma was used as an index of oxidant free radical activity. The study was performed in two groups of patients. Group A (n = 11) had studies extending over the entire operative period and showed a highly significant sequestration of neutrophils into the lung, together with a highly significant (p less than 0.001) rise in peroxidation products from 2.8 +/- 0.12 nmol/ml(mean +/- standard error of the mean)before bypass to a peak of 5.05 +/- 0.13 nmol/ml at the end of bypass. As these changes occurred only during the time after release of the aortic cross-clamp, we investigated this period in more detail in a second group of patients (Group B, n = 7). Results from this group showed that significant release of peroxidation products occurred at the same time as pulmonary neutrophil sequestration. This study has produced evidence of increased oxidant activity in the lung associated with cardiac operations. Nevertheless, it is not known whether the neutrophils sequestered into the lung alone induced the increased activity. Similarly, whether neutrophil-derived oxidant species are the sole cause of lung tissue injury remains unproved.