Effects of topical application of free and liposome-encapsulated lactoferrin and lactoperoxidase on oral microbiota and dental caries in rats.

Four groups of rats were inoculated with Streptococcus sobrinus ATCC 33478 and fed a cariogenic diet for 42 days. Topical treatment with either distilled water, sodium fluoride (0.2%), a solution containing lactoferrin and lactoperoxidase, or a solution containing liposome-encapsulated lactoferrin and liposome-encapsulated lactoperoxidase was applied at intervals for 35 days. Caries incidence in groups treated with liposome-encapsulated lactoferrin and lactoperoxidase was significantly lower than in control groups. The number of viable Strep. sobrinus and the proportion of Strep. sobrinus in the total counts were significantly higher in liposome-treated groups. Free lactoferrin and lactoperoxidase did not cause a significant reduction in caries incidence.

Oral metamizol (1 g and 2 g) versus ibuprofen and placebo in the treatment of lower third molar surgery pain: randomised double-blind multi-centre study. Cooperative Study Group.

OBJECTIVE: To assess the efficacy of metamizol 1 g and 2 g in the relief of pain after surgical extraction of the lower third molar, and to compare the therapeutic effect with that of ibuprofen 600 mg or placebo. METHODS: A total of 253 patients aged between 18 years and 60 years who had undergone extraction of the lower third molar (types II-IV) under local anaesthesia, up to a maximum of 108 mg of mepivacaine, were randomly assigned to a single oral dose of a new galenic form (drinkable vials) of metamizol 1 g (n = 75), metamizol 2 g (n = 72), ibuprofen 600 mg (n = 74) or placebo (n = 32). Pain intensity was evaluated by a 100-mm visual analogue scale. To enter the study, a pain level of 50 mm or more was required. The duration of the trial was 1 h. Assessments were carried out at 15, 30 and 60 min after treatment. RESULTS: The analgesic efficacy of metamizol 2 g was significantly better than ibuprofen and placebo with regard to all evaluated parameters. The values of the pain intensity difference at 15 min, the percentage of patients with a decrease of 50% or more on the visual analogue scale at 60 min and the sum of pain intensity differences at 60 min showed metamizol 2 g to be significantly more effective than metamizol 1 g. In general, metamizol 1 g was as effective as ibuprofen 600 mg. The analgesic efficacy of placebo was significantly lower than that of all active treatments. A lower number of patients treated with metamizol 1 g (n = 1) or metamizol 2 g (n = 1) needed rescue medication than those given ibuprofen (n = 7) or placebo (n = 5). No serious adverse effects developed and none of the patients had to leave the study for this reason. CONCLUSIONS: The model of the lower third molar, for which the analgesic outcome referred to the first hour after drug administration, demonstrated that the analgesic efficacy of oral metamizol 2 g was significantly higher than that of ibuprofen 600 mg or placebo. Metamizol 1 g and ibuprofen 600 mg showed a similar therapeutic effect. All regimens were as well tolerated as placebo.

Protective effect of nifedipine against carrageenan-induced inflammation.

Administration of carrageenan (CA; 0.5 mg) to the plantar tissue of rats resulted in reversible inflammatory injury. The edema was monitored by changes in paw volume using a plethysmometer. Simultaneous administration of CA and nifedipine, intraperitoneally, at different doses (10, 20 and 50 mg/kg) prevented the inflammatory action, and the effect was dose- and time-dependent. In order to improve the nifedipine effects, we prepared liposomed nifedipine which, administered intraperitoneally, showed a greater anti-inflammatory action. In the presence of the L-type channel agonist Bay K 8644, the inflammation produced by CA increased and it was counteracted by free or liposomed nifedipine. The significance of these findings with respect to the mechanism of the anti-inflammatory action of nifedipine is discussed.

Fluoride and pilocarpine reduce the risk of caries produced by chronic clomipramine treatment in rats.

The effects of chronic clomipramine treatment on the incidence of caries in the rat and their prevention by fluoride and pilocarpine were investigated. One hundred and twenty male Wistar rats were divided into six groups, five experimental groups, one control group and treated with 50 mg/kg/day of clomipramine, 10 ppm fluoride in drinking water, and 5 mg/kg/day of pilocarpine. All animals were infected with Streptococcus sobrinus 6715 and fed a cariogenic diet ad libitum for 42 days. Water and food consumption, weight gain, salivary flow rate, amylase activity, protein and fluoride concentration in saliva, and caries scores were determined in all animals. Whereas clomipramine significantly increased the fluoride and protein concentration in saliva, pilocarpine only decreased fluoride concentration. Animals treated with clomipramine developed 40% more sulcal caries than nontreated animals. Administration of fluoride (10 ppm) in drinking water and chronic oral administration of pilocarpine prevented the increased risk of developing caries associated with chronic treatment with clomipramine.

Pharmacological evidence for the involvement of the endogenous opioid system in the response to local inflammation in the rat paw.

We have investigated the role of the endogenous opioid system (EOS) on the inflammatory response induced by subplantar (s.p.) injection of saline (SS) and carrageenan (CA) in the hindpaw of the rat. The administration of intraperitoneal (i.p.) naloxone was used in order to unmask the effects of endogenous opiates released during peripheral inflammation. Three groups of rats received one of the following s.p. treatments: SS, CA, or no injection (NI). Pain pressure threshold (PPT), paw volume (edema) and local temperature were evaluated in baseline conditions and 3 h after treatment. In each group, the effects of i.p. vehicle, naloxone and (+)-naloxone (0.1 mg/kg) were also investigated. Both SS and CA induced a significant inflammatory response with hyperalgesia, edema and local hyperthermia. The i.p. administration of naloxone but not that of (+)-naloxone 15 min prior to testing, significantly increased edema in all groups of treatment (P < 0.05), without altering PPT or local temperature. Two-way ANOVA revealed that treatment and drugs, as well as their interaction, had a significant impact on edema which was related to the effects of CA and naloxone. Our findings illustrate the involvement of the EOS in the physiological response to local injury, regulating microvascular leakage in the inflamed tissues.

Protective effect of fructose 1,6-bisphosphate against carrageenan-induced inflammation.

Administration of carrageenan (0.5 mg) to the plantar tissue of rats resulted in reversible inflammatory injury. This damage was monitored as changes in foot volume, using a plethysmometer. Administration of fructose 1,6-bisphosphate at different doses, orally or intraperitoneally, prevented the inflammatory action induced by the simultaneous injection of carrageenan in the rat paw. The effect was dose and time dependent. In contrast, fructose or fructose 6-phosphate afforded no significant protection. In order to extend the average half-life of the drug, we prepared liposomes of fructose 1,6-bisphosphate which, administered orally or intraperitoneally, showed a greater and more prolonged antiinflammatory action. The significance of these findings with respect to the mechanism of the antiinflammatory action of fructose 1,6-bisphosphate is discussed.

Noninvasive percutaneous induction of topical analgesia by a new type of drug carrier, and prolongation of local pain insensitivity by anesthetic liposomes.

We studied the duration of action and permeability of common analgesics and local anesthetics applied dermally via new carriers--transfersomes--in rats and humans. The therapeutic potential of analgesic transfersomes was evaluated in Sprague-Dawley rats subjected to heat and pressure stimuli. Results were compared with those obtained from administration of lidocaine-containing standard liposomes. In rats, subcutaneous injections of 2% lidocaine solution and of liposomal or transfersomal suspension resulted in a strong initial analgesic effect that decayed within 6-7 min. Characteristic withdrawal time is approximately 30 s. Dermally applied analgesic transfersomes, by contrast, increased heat stimulus reaction to greater than 70 s, 130% longer than in controls that received a placebo or a standard aqueous lidocaine solution. In humans, we tested two groups of nine male and female volunteers, aged between 25 and 60 yr, for pain-suppressing activity assessed by the pinprick method. Each subject received a total of 0.5 mL of a transfersomal preparation containing 7% lidocaine or 4% tetracaine over a forearm area of 9 cm. We conclude that the effectiveness of dermally applied anesthetic transfersomes is similar to that of the corresponding subcutaneous injections of similar drug quantities and that optimally designed transfersomes offer a suitable and promising means for the noninvasive treatment of local pain with direct, topical drug application.