The role of ozonized oil and a combination of tobramycin/dexamethasone eye drops in the treatment of viral conjunctivitis: a randomized clinical trial.

PURPOSE: To determine whether topical tobramycin 0.3%/dexamethasone 0.1% plus ozonized oil eye drops reduces clinical signs and infectious viral titers of presumed viral conjunctivitis more than tobramycin/dexamethasone eye drops alone. METHODS: Prospective, single-blind, randomized, parallel-groups trial. Eighty patients with a clinical diagnosis of presumed viral conjunctivitis were randomizedly divided into two treatment groups: a study group and a control group, 40 for each group. Patients in the study group received topical tobramycin 0.3%/dexamethasone 0.1% eye drops, plus ozonized oil eye drops, both four times daily; patients in the control group received only topical tobramycin 0.3%/dexamethasone eye drops four times daily. The treatment was for seven days in both groups. Swabs were taken from the conjunctival fornix for adenovirus PCR analysis on the day of recruitment and at seven days follow-up. Clinical signs were also recorded on the day of recruitment and at follow-up examination: the main outcomes were conjunctival injection and conjunctival chemosis, graded on a 4-point clinical scale, presence or absence of superficial punctate keratitis and subepithelial corneal infiltrates. RESULTS: No statistically significant difference was reached in adenoviral infection negativization between the two groups, although the study group showed a higher number of PCR negative results at seven days follow-up. PCR real time detected adenoviral infection in 17 of 24 patients on the day of recruitment and it was positive in 4 patients on the seventh day (viral positivity reduction of 76%). In the control group PCR was positive for adenovirus in 18 of 24 patients on the day of recruitment and in 7 patients at seven days follow-up (reduction of 61%). There was statistically significant difference on conjunctival clinical signs between the study and control groups. Significant difference was also found on superficial punctate keratitis resolution between the study and the control group. In the former superficial punctate keratitis was detected in 14 eyes on the first day and in 5 eyes after seven days while in the latter superficial punctate keratitis was found in 124 eyes on the first day and in 6 eyes on the seventh day. No difference was found in subepithelial corneal infiltrates appearance between the two groups. CONCLUSIONS: The use of ozonized-oil containing eye drops in combination with topical tobramycin 0.3%/dexamethasone 0.1% eye drops four times daily seems to reduce the signs of conjunctivitis, and the duration of viral infection, although it does not affect the subepithelial corneal infiltrates appearance.

Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) activity in PARP-1 silenced tumour cells increases chemosensitivity to temozolomide and to a N3-adenine selective methylating agent.

We recently demonstrated that poly(ADP-ribose) polymerase (PARP)-1 is involved in angiogenesis and tumour aggressiveness. In this study we have compared the influence of abrogation of PARP-1 expression by stable gene silencing to that of the pharmacological inhibition of cellular PARP activity using PARP-1/-2 inhibitors on the chemosensitivity of tumour cells to the wide spectrum methylating agent temozolomide (TMZ) and to the N3-adenine selective methylating agent {1-methyl-4-[1-methyl-4-(3-methoxysulfonylpropanamido)pyrrole-2-carboxamido]-pyrrole-2-carboxamido}propane (Me-Lex). Silencing of PARP-1 in melanoma or cervical carcinoma lines enhanced in vitro sensitivity to TMZ and Me- Lex, and induced a higher level of cell accumulation at the G2/M phase of cell cycle with respect to controls. GPI 15427, which inhibits both PARP-1 and PARP-2, increased sensitivity to TMZ and Me-Lex both in PARP-1-proficient and - deficient cells. However, it induced different cell cycle modulations depending on PARP-1 expression, provoking a G2/M arrest only in PARP-1 silenced cells. Treatment of PARP-1 silenced cells with TMZ or Me-Lex resulted in a more extensive phosphorylation of Chk-1 and p53 as compared to PARP-1 proficient cells. The combination of the methylating agents with GPI 15427 increased Chk-1 and p53 phosphorylation both in PARP-1 proficient or deficient cells. When mice challenged with PARP-1 silenced melanoma cells were treated with the TMZ and PARP inhibitor combination there was an additional reduction in tumour growth with respect to treatment with TMZ alone. These results suggest the involvement of PARP-2 or other PARPs, in the repair of DNA damage provoked by methylating agents, highlighting the importance of targeting both PARP-1 and PARP-2 for cancer therapy.

Transient ischaemia refractory to conventional medical treatment in unstable angina: angiographic correlates and prognostic implications.

Complex stenosis morphology is frequently seen in patients with unstable angina. However, its relation to transient myocardial ischaemia and clinical outcome has not been adequately elucidated. We studied 86 patients admitted to the Coronary Care Unit for unstable angina; all patients underwent ECG Holter monitoring during the first 2-4 days, while receiving intensive triple drug treatment. Coronary angiography and subsequent analysis of the ischaemia-related artery were performed within 12 days of admission. Patients were grouped according to their angiographic features: 45 showed complex coronary morphology (CM: 29 eccentric stenosis with irregular borders or overhanging edges; 16 intracoronary thrombus), 11 had documented coronary spasm as well as moderate atherosclerosis (CS), seven had left main coronary artery disease, and the remaining 23 patients showed regular and smooth morphology of coronary stenosis (RM). At admission, transient myocardial ischaemia (TMI) was greater in patients with CM (85 +/- 60 min .24 h-1) than in those with RM or CS (33 +/- 26 min .24 h-1; P less than 0.005). After 3 days of full medical treatment TMI decreased in all groups, but 34/45 patients with CM and 9/34 with RM or CS still showed residual ischaemia (greater than 0 min .24 h-1): 76% vs 26%, P less than 0.02. Follow-up was obtained at hospital discharge and after 1 year in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic morphology in unstable angina and its relation to transient myocardial ischemia and hospital outcome.

Complex stenosis morphology frequently occurs in patients with unstable angina pectoris. However, its relation to transient myocardial ischemia and hospital outcome has not been ascertained. To address this issue, 88 patients with significant (greater than or equal to 50%) coronary artery disease presenting with angina--new onset (n = 38), worsening (n = 20) or at rest (n = 30)-were studied. Patients with left main artery disease, normal coronary arteries or occlusion of the ischemia-related arteries were not included in the study. Continuous electrocardiographic recordings were obtained during the first 24 hours. Angiography was performed within 1 week from admission. Complex morphology was defined as any stenosis with irregular borders, overhanging edges or intracoronary thrombus. Only data referring to the in-hospital outcome were considered in this study. Adverse end points were sudden death, myocardial infarction and emergency revascularization. Analysis of the angiograms revealed a complex morphology in 58 patients (group 1). The remaining 30 patients served as control subjects (group 2). Thirty-two of the 58 group 1 patients had an unfavorable clinical outcome (positive predictive value, 55%). A similar outcome occurred in only 2 of the 30 group 2 patients (negative predictive value, 93%). Of the 32 group 1 patients who had an unfavorable clinical outcome, 29 had a cumulative duration of transient myocardial ischemia of greater than or equal to 60 minutes per 24 hours. A similar duration of ischemia, however, was observed in another 6 group 1 and in 8 group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)