Immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a potent anti-HIV nucleotide analogue, on in vivo murine models.

In order to evaluate the influence of antiviral nucleoside analogues upon the natural immune system, we investigated the immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a nucleotide analogue with potent anti-HIV and anti-herpes activity, in a murine system. C57BL/6 mice were inoculated intraperitoneally with 10, 25 and 50 mg PMEA/kg. Mononuclear cells were isolated from their spleens, and some natural immune functions were evaluated. The results show that PMEA significantly increases the levels of natural killer (NK)-cell cytotoxicity. We also found that alpha/beta IFN production was substantially increased in PMEA-treated mice, while both IL-1 and IL-2 production was decreased. Thus, PMEA can increase some natural immunity functions, such as NK activity and IFN production. These results suggest that PMEA might be active in vivo against HIV and herpes viruses both as an immunomodulator and as an antiviral compound.     

Iopamidol and meglumine diatrizoate: comparison of effects on patient discomfort during aortofemoral arteriography

Iopamidol was compared with Renografin-60 (meglumine diatrizoate, Squibb) in a controlled, randomized double-blind study of 40 patients undergoing peripheral arteriography for arteriosclerotic occlusive disease to determine which agent caused less discomfort. Each patient was evaluated for objective signs of discomfort and subjective feelings of pain and heat. Monitoring was achieved by multiple physical examinations, chemical tests, electrocardiograms, and intra-arterial pressure recordings. It is concluded that iopamidol is safe and causes significantly less patient discomfort than Renografin-60.     

TRILINOLEIN INHIBITS THE ADHESION OF NEUTROPHILS TO ENDOTHELIAL CELLS

1. Trilinolein is a triacylglycerol with linoleic acid as the only type of fatty acid in all three esterified positions of glycerol. It was recently reported to have a myocardial protective effect in coronary ligated rats. We now study its effect on the adhesion of human neutrophils to cultured bovine endothelial cells. 2. Pretreatment of an endothelial monolayer with trilinolein at concentrations ranging from 10^-10 to 10^-6 mol/L significantly inhibited neutrophil adhesion to endothelial cells. Trilinolein was less potent than sodium nitroprusside in inhibiting neutrophil adhesion. 3. The inhibitory effect of trilinolein was antagonized by methylene blue and N^G-nitro-L-arginine methyl ester. The inhibitory effect of trilinolein was not mediated through linoleic acid because linoleic acid did not inhibit neutrophil adhesion. 4. Pretreatment of neutrophils with trilinolein did not reduce neutrophil adhesion. However, in neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine, trilinolein inhibited the neutrophil adhesion to endothelial cells. 5. We conclude that trilinolein inhibits neutrophil adhesion to the endothelial monolayer by stimulating the nitric oxide and cyclic GMP pathways in endothelial cells. It may also inhibit neutrophil adhesion by scavenging free radicals. The inhibitory effect of trilinolein on neutrophil adhesion may play a role in its myocardial protective activity.     

Outpatient lumbar myelography. Initial results in 79 examinations using a low-dose metrizamide technique

Seventy-nine patients underwent lumbar myelography on an outpatient basis, with a low (3.75 g) dose of metrizamide as the radiocontrast agent and a 25-gauge spinal needle used for lumbar puncture. No patient experienced significant neurotoxicity following the examination; 70.8% (56 of 79) experienced minimal (23%) or no (48%) side effects. Three patients (3.8%) were admitted to the hospital for management of common side effects (headache, nausea/vomiting, back pain). We obtained postmyelographic computed tomographic scans on 96% (76 of 79) of the patients. Our initial results suggest that outpatient lumbar myelography is safe and can be performed with a very acceptable incidence of side effects.     

Different pattern of activity of inhibitors of the human immunodeficiency virus in lymphocytes and monocyte/macrophages.

Monocyte/macrophages (M/M) are important targets for HIV in the body, and represent the majority of cells infected by the virus in some body compartments such as the central nervous system (CNS). M/M can be different from T-lymphocytes in terms of surface antigens, cell replication and drug metabolism. Thus, we evaluated, in M/M and in T-lymphocytes, the pattern of viral inhibition induced by various anti-HIV drugs, and assessed some of the mechanisms of action related to such antiviral activity. Inhibitors of HIV binding on CD4 receptors have similar activity in M/M and T-lymphocytes, while AZT and other dideoxynucleosides (ddN) are in general more active against HIV in M/M than in T-lymphocytes. This phenomenon can be related to the increased ratio in M/M of ddN-triphosphate/deoxynucleoside-triphosphate, and can at least in part explain the ability of zidovudine and didanosine in improving neurological dysfunctions in AIDS patients. Moreover, the antiviral activity of AZT (but not of other ddN- or HIV-binding inhibitors) is potently enhanced by cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF) in M/M, while anti-HIV activity of TIBO compounds in M/M is not down-modulated by GM-CSF and other cytokines. Finally, non-toxic concentrations of adriamycin, an anticancer drug reported to be active against DNA viruses, can inhibit HIV replication in M/M (but not in T-lymphocytes). Taken together, these results suggest that M/M are selective targets for HIV with peculiarities different from those of T-lymphocytes. Thus, promising anti-HIV compounds should be evaluated both in T-cells and in M/M before reaching clinical trials. This may help in selecting drugs with good chances of being effective in patients with HIV-related disease.     

Effect of postpartum maternal infection on proteins and trace elements in colostrum and early milk

In developing countries, maternal infections during lactation are common. In this study, we evaluated the effect of acute maternal postpartum infection on the composition of colostrum and early milk with special emphasis on milk proteins and trace elements. The study was carried out in two maternity hospitals in Lima, Peru. Subjects were normally nourished women (body mass index (BMI) > 20.0) who intended to exclusively breastfeed their child and who had fever and clinical symptoms of infection within the first 48 h postpartum ( n = 34). Non-ill women of similar characteristics were selected as controls ( n = 23). Blood and milk samples were taken on days 1 and 14 postpartum. An acute phase response was confirmed by significantly increased serum levels of C-reactive protein in infected women. Serum zinc levels increased significantly from day 1 to day 14, but were not affected by infection. Serum copper levels were significantly higher in ill women than in non-ill women on day 1. All participating women were breastfeeding on day 14. Whey protein levels, the whey/casein ratio and total protein levels decreased significantly with time, but were not affected by infection. There were no differences in milk iron or copper levels with time or infection. Milk zinc levels decreased significantly with time, but were not affected by infection. Maternal infection during the early postpartum period does not appear to adversely affect the initiation of lactation or milk protein and trace element contents.