Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids

The effects of essential fatty acids on cell proliferation and cell viability of 3 human tumor and 4 normal cell lines were tested in vitro. It was found that n-3 and n-6 fatty acids supplemented at 20 micrograms/ml killed human breast, lung, and prostate cancer cells selectively. Normal human fibroblasts and other normal cells were not killed, but their rate of division was lowered. The most selective cytotoxic effects were obtained with fatty acids containing 3, 4, and 5 double bonds. The degree of inhibition of growth and/or loss of viability depended on a given fatty acid, on cell density, on fatty acid concentration, and on the type of cell. When eicosapentaenoate, gammalinolenate, or arachidonate was added to cocultures made of human cancer cells with normal fibroblasts, the cancer cells were selectively eliminated. These results, combined with the observation that certain fatty acids coupled to cytotoxic agents may enhance the cytotoxic activity, suggest that treatment of cancer with polyunsaturated fatty acids containing 3, 4, and 5 double bonds has potential clinical usefulness.     

Wall-eyed bilateral internuclear ophthalmoplegia (Webino syndrome) and myelopathy in pyoderma gangrenosum

A 35-year-old female with pyoderma gangrenosum developed paraparesis with a sensory level at L1. Three months later she complained of diplopia and was found to have bilateral internuclear ophthalmoplegia with exotropia and no ocular convergence. The term Webino syndrome has been coined to design this set of neuro-ophthalmologic findings. Although it was initially attributed to lesions affecting the medial longitudinal fasciculus and the medial rectus subnuclei of the oculomotor complex in the midbrain the exact location of the lesion is still disputed. In the present case both myelopathy and Webino syndrome were probably due to vascular occlusive disease resulting from central nervous system vasculitis occurring in concomitance to pyoderma gangrenosum.     

Sjögren syndrome: comparative studies in local ocular and serum immunoglobulin concentrations with special reference to secretory IgA

The objective of the present study was to examine Secretory IgA in tears and serum of Sjögren patients (34 patients and 23 controls). The test was performed in a parallel study using a polyclonal and a monoclonal method (Inter-Assay variation 9.1/Intra-Assay variation 5.5). No differences in the levels of tear secretory IgA were found between patients and controls. In serum however, secretory IgA, total IgA, IgM and IgG showed a significant increase in the Sjögren patients. The fact that secretory IgA levels remain normal in the ocular mucosa of these patients may explain that, despite the autoimmune destruction of the lacrimal gland, humoral defense factors are normally present on the surface of the eye to combat infections.     

Recurrence of vancomycin-resistant Enterococcus stool colonization during antibiotic therapy.

OBJECTIVE: To test the hypothesis that antibiotic therapy may promote recurrence of vancomycin-resistant Enterococcus (VRE) stool colonization in patients who have previously had three consecutive negative stool cultures obtained at least 1 week apart. DESIGN: One-year prospective cohort study examining the effect of antibiotic therapy on recurrence and density of VRE stool colonization in patients who have cleared colonization. Pulsed-field gel electrophoresis (PFGE) was performed to determine whether recurrent VRE strains were the same clone as the previous colonizing strain. SETTING: A Department of Veterans Affairs medical center including an acute care hospital and nursing home. PATIENTS: All patients with at least one stool culture positive for VRE who subsequently had three consecutive negative stool cultures obtained at least 1 week apart. RESULTS: Of the 16 patients who cleared VRE colonization, 13 received antibiotic therapy during the study period. Eight (62%) of the 13 patients who received antibiotics developed recurrent high-density VRE stool colonization (range, 4.9 to 9.1 log10 colony-forming units per gram) during a course of therapy. Five patients had VRE strains available for PFGE analysis; recurrent strains were unrelated to the prior strain in 3 patients, closely related in 1 patient, and indistinguishable in 1 patient. CONCLUSIONS: Antibiotic therapy may be associated with recurrent high-density VRE stool colonization in many patients who have previously had three consecutive negative stool cultures. These patients should be screened for recurrent stool colonization when antibiotic therapy is administered.     

Membrane–cytoskeleton interactions during the formation of the immunological synapse and subsequent T-cell activation

Summary: Upon antigen recognition, T cells undergo substantial membrane and cytoskeletal rearrangements that lead to the formation of the immunological synapse and are necessary for subsequent T‐cell activation. However, little is known about how membrane and cytoskeletal molecules interact during these processes. Here we discuss the involvement of the membrane‐microfilament linker ezrin. We propose that ezrin is a component of the cytoskeleton‐mediated architecture of the immunological synapse that plays a role in T‐cell receptor clustering, protein kinase C θ translocation and intracellular signaling.     

Pentoxifyline versus prednisolone for severe alcoholic hepatitis: A randomized controlled trial

AIM: To compare the efficacy of pentoxifylline and prednisolone in the treatment of severe alcoholic hepatitis, and to evaluate the role of different liver function scores in predicting prognosis. METHODS: Sixty-eight patients with severe alcoholic hepatitis (Maddrey score ≥ 32) received pentoxifylline ( n = 34, group Ⅰ) or prednisolone ( n = 34, group Ⅱ) for 28 d in a randomized double-blind controlled study, and subsequently in an open study (with a tapering dose of prednisolone) for a total of 3 mo, and were followed up over a period of 12 mo. RESULTS: Twelve patients in group Ⅱ died at the end of 3 mo in contrast to five patients in group Ⅰ. The probability of dying at the end of 3 mo was higher in group Ⅱ as compared to group Ⅰ (35.29% vs 14.71%, P = 0.04; log rank test). Six patients in group Ⅱ developed hepatorenal syndrome as compared to none in group Ⅰ. Pentoxifylline was associated with a significantly lower model for end-stage liver disease (MELD) score at the end of 28 d of therapy (15.53 Maddrey score was associated with increased mortality. CONCLUSION: Reduced mortality, improved risk-benefit profile and renoprotective effects of pentoxifylline compared with prednisolone suggest that pentoxifylline is superior to prednisolone for treatment of severe alcoholic hepatitis.