Inhibition of platelet aggregation by putrescine, spermidine, and spermine in hypercholesterolemic rabbits.

BACKGROUND: Hypercholesterolemia causes alterations in platelet function. Platelet hyperaggregation is considered a predisposing factor for atherosclerosis. In this paper, the antiaggregating effect of the polyamines putrescine, spermidine, and spermine was studied on platelets of normal and hypercholesterolemic rabbits. METHODS: New Zealand rabbits were fed with a cholesterol-enriched diet for 10 weeks. Lipids and glucose were determined in serum. The assays of platelet aggregation were carried out using platelet-rich plasma (PRP) obtained from both control and cholesterol-fed rabbits. We used 2.5 micromol /mL ADP and 2 microg/mL collagen as inductors of platelet aggregation. In addition, arginase activity and L-arginine content were determined in PRP. RESULTS: Serum total cholesterol and LDL-cholesterol concentrations were increased from 26.3 +/- 8.1 to 1,485.0 +/- 26.8 mg/dL and from 15.9 +/- 5.9 to 1,383.8 +/- 58.9 mg/dL, respectively, whereas triglyceride concentration increased from 88.3 +/- 35.6 to 411.0 +/- 154.5 mg/dL upon cholesterol feeding. Seventy-five percent of platelet aggregation inhibition was observed with 10 microM of polyamines in PRP of normal rabbits. Spermine inhibited platelet aggregation by 54% in PRP of hypercholesterolemic rabbits when ADP was used as agonist. The order of polyamine action was spermine > spermidine > putrescine. In addition, we found that platelet arginase activity and L-arginine content were unaltered upon hypercholesterolemia. CONCLUSIONS: These results show that the polyamines putrescine, spermidine, and spermine have antagonist action in platelet aggregation and suggest a key role of polyamines in platelet aggregation under normal and hypercholesterolemic conditions.

Systemic IFN-alpha treatment of multiple bladder papilloma grade I or II patients: pilot study.

Bladder papillomatosis offers a good target to evaluate IFN-alpha systemic treatment. We carried out a pilot study on eight multiple bladder papilloma patients under the same treatment scheme (1 x 10(6) IU/amp. every 48 h over six months), and they were followed-up for over two years after treatment. Recurrent patients underwent a similar second treatment. IFN-alpha therapy showed the following variations of effects: total disappearance, size decrease or persistence of papillomas, neither size increase nor appearance of new ones, remarkable valuable recurrence frequency rate decrease in all cases, and recurrences with smaller papillomas. This IFN-alpha treatment scheme would be fit to carry out broader controlled studies to show frequencies of the different kinds of responses. The inclusion of a minimum (dose-frequency-period) IFN-alpha treatment period after the first six months' therapy is proposed in order to achieve total disappearance of recurrences.

Influence of human leukocyte interferon on IgG on the replication of herpes simplex virus in nervous tissue in vitro.

Herpes simplex virus type 1 (HSV-1) replicated productively in rabbit and guinea pig ganglia and nerve organ cultures when inoculated in high titres. Treatment with IgG 20 hr before and 48 hr after infection produced a delay of 4 to 7 days in the recovery of HSV-1 by the method of co-cultivation. The same result was obtained when IgG was combined with human leukocyte interferon. There was no difference in the period up to HSV recovery between the groups treated with interferon alone and the HSV control. Morphological evidence by light and electron microscopy of viral productive infection was obtained in all the cell types of nervous tissues infected in vitro.

Combined therapy of human interferon (HI) and secretory immunoglobulin (S-IgA) in the treatment of human herpetic keratitis.

The topical action of a combined therapy of human interferon (3000 U/ml) and secretory immunoglobulin IgA (1,5 mg/ml) was studied in 56 patients with herpetic keratitis. The pain and photophobia disappeared within 48 h after the beginning of treatment and a marked reduction of the corneal lesion during the first week of treatment was observed in all the patients. The therapy was effective, with complete healing of the lesion in 94.8% of cases; 72.2% of them healed in less than 15 days. The highest frequency of healing was between 5 and 10 days, and the rest up to 30 days. Humoral, immunological and delayed hypersensitivity studies were carried out in 36 patients.

Interferon in the replication of herpes simplex virus in normal and pathological nerve cells.

Previous results obtained in experimental and clinical trials have demonstrated that topical combined thrapy with human interferon (HI) and human colostral secretory immunoglobulin A (S-IgA) is effective against herpetic corneal infection. This therapy prevented encephalitis in rabbits but could not completely prevent recurrences either in rabbits or in patients. A number of in vitro studies were designed to elucidate the role of these factors in herpes simplex virus replication in the nervous system, with the following results: (1) HSV latency in trigeminal ganglia (TG) explanted from rabbits with experimental herpetic keratitis, topically treated with HI or HI/S-IgA: HSV was recovered in 30% TG after 15-19 days co-cultivation on RK-13 cells. (2) HSV replication in nervous ganglia and nerve of newborn rabbits in organ culture; influence of HI or HI plus IgG: a restrictive HSV productive infection was demonstrated in this system, although yields were always higher in nerve cultures. We were unable to demonstrate a direct effect of HI on HSV-1 replication. When explants were treated with HI and IgG before and after infection for 48 hours a delay in the expression of HSV-1 was detected by co-cultivation. (3) Replication of HSV-1 and HSV-2 in a C1300 murine neuroblastoma clone (NB41A3): both HSV types replicated with titres of 10(3.4) for HSV-1 AND 10(4.8) for HSV-2 at 48 hours p.i.; CPE was more marked for HSV-2 at 24 hours. HSV-specific antigens were demonstrated by the immunoperoxidase technique.