Study of the action of antineoplastic drugs (methotrexate) on DNA structure both in vitro and in vivo

In the present study we examined the antineoplastic effects of methotrexate and its combinations with caffeine hyperthermia and caffeine with hyperthermia together on normal human lymphocytes in vitro. The effects of the above agents on normal human lymphocytes were evaluated through the simultaneous study of the 3 cytogenetic indicators: a) the SCEs/cell, b) the proliferating rate index and c) the mitotic index. Also, we examined the in vivo effects of methotrexate and its combination with caffeine on laboratory animals with Ehrlich cancer through the simultaneous study of both the survival span of the experimental animals and the rate of the increase of the weight of their tumours. The results of our experiments indicated that methotrexate and its combinations with caffeine, hyperthermia and caffeine with hyperthermia together increased the SCEs/cell levels and reduced both the proliferating rate index and the mitotic index. Also both methotrexate and its combinations with caffeine increased the survival span of the experimental animals and reduced the rate of the increase of the weight of their tumours. Consequently, it is possible to achieve increased effectiveness of methotrexate, and better therapy results with fewer side effects if together with methotrexate caffeine is administered in non-toxic doses and if hyperthermia is applied.Στην παρούσα εργασία μελετήσαμε την αντινεοπλασματική δράση της μεθοτρεξάτης και των συνδυασμών της με την καφεΐνη, την υπερθερμία και την καφεΐνη με την υπερθερμία μαζί σε καλλιέργειες φυσιολογικών λεμφοκυττάρων ανθρώπου in vitro, με την ταυτόχρονη αξιολόγηση των ακολούθων 3 κυτταρογενετικών δεικτών: α) των SCEs, β) του δείκτη ρυθμού πολλαπλασιασμού και γ) του μιτωτικού δείκτη. Επίσης μελετήσαμε την in vivo δράση της μεθοτρεξάτης και του συνδυασμού της με την καφεΐνη σε πειραματόζωα με καρκίνο του Εrhlich, με την ταυτόχρονη αξιολόγηση της επιβίωσης και της αύξησης του βάρους του όγκου τους την 8η ημέρα. Τα αποτελέσματα των πειραμάτων έδειξαν ότι τόσο η μεθοτρεξάτη όσο και οι συνδυασμοί της με την καφεΐνη, την υπερθερμία και την καφεΐνη με την υπερθερμία μαζί προκάλεσαν αύξηση των επιπέδων των SCEs/κύτταρο και ελάττωση των τιμών του δείκτη ρυθμού πολλαπλασιασμού και του μιτωτικού δείκτη. Επίσης, η μεθοτρεξάτη και ο συνδυασμός της με την καφεΐνη αύξησαν την επιβίωση των πειραματόζωων και μείωσαν το ρυθμό της αύξησης του βάρους του όγκου τους. Συνεπώς, φαίνεται ότι η δραστικότητα της μεθοτρεξάτης αυξάνεται και οι ανεπιθύμητες ενέργειές της ελαττώνονται όταν ταυτόχρονα με αυτή χορηγείται καφεΐνη σε μη τοξικές δόσεις και εφαρμόζεται υπερθερμία. Επίσης, είναι δυνατόν ο παραπάνω τριπλός συνδυασμός να χρησιμοποιηθεί με επιτυχία στην αντιμετώπιση διαφόρων μορφών καρκίνου στον άνθρωπο, όπου η μεθοτρεξάτη βρίσκει σήμερα εφαρμογή σε συνδυασμό με άλλους παράγοντες

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension

PURPOSE. The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS. This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were ≥24 mmHg at 9 AM and ≥21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12. RESULTS. Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant. CONCLUSIONS. Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH.8 page(s

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension

European Journal of Ophthalmology172183-190EJOO