Natural rubber latex used as drug delivery system in guided bone regeneration (GBR)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metronidazole release using natural rubber latex as matrix

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The controlled release of antibiotic by hydroxyapatite: Anionic collagen composites

Major problems with the treatment of osteomyelitis are associated with poor antibiotic distribution at the site of infection due to limited blood circulation to the skeletal tissue. Improved treatment procedures have been used in drug delivery systems that include bioceramics and natural and synthetic polymers. This work reports the development of anionic collagen:hydroxyapatite composite paste for sustained antibiotic release. Antibiotic release by the composite was characterized by two steps. In the first, 15.0 +/- 4.9% was released in the first 5 h (n = 53) by a normal Fick diffusion mechanism. In the second step, only 16.8 +/- 2.2% was released after 7 days. In conclusion, hydroxyapatite:anionic collagen composite can be an efficient support for sustained antibiotic release in the treatment of osteomyelitis because most of the antibiotic release may be associated with composite bioresorption, thus permitting antibiotic release throughout the healing process. Hydroxyapatite:anionic collagen paste showed good biocompatibility associated with bone tissue growth with material still being observed after 60 days from the time of implants.

AC biosusceptometry in the study of drug delivery

Conventionally, pharmaceutical substances are administered orally because the gastrointestinal tract possesses the appropriate features for drug absorption. Nevertheless, the gastrointestinal tract physiology is complex and influenced by many factors. These factors must be completely understood for the optimization of oral drug delivery systems. Although in vitro tests provide information about release and drug absorption profiles, in vivo studies are essential, due to the biological variability. Several techniques have been employed in an attempt to conveniently characterize the behavior of solid dosage forms in vivo. The noninvasive biomagnetic technique of alternate current biosusceptometry (ACB) has been used in studies focusing on gastrointestinal motility and, more recently, to evaluate the performance of magnetic dosage forms. This article will discuss the main characteristics of AC biosusceptometry and its applicability for determination of the relationship between the human gastrointestinal tract and orally administered pharmaceutical dosage forms. (c) 2005 Elsevier B.V. All rights reserved.

Water regulation of actinomycin-D binding to DNA: the interplay among drug affinity, DNA long-range conformation, and hydration

Actiaomycin-D (actD) binds to natural DNA at two different classes of binding sites, weak and strong. The affinity for these sites is highly dependent on DNA se(sequence and solution conditions, and the interaction appears to be purely entropic driven Although the entropic character of this reaction has been attributed to the release of water molecules upon drug to DNA complex formation, the mechanism by which hydration regulates actD binding and discrimination between different classes of binding sites on natural DNA is still unknown. In this work, we investigate the role of hydration on this reaction using the osmotic stress method. We skew that the decrease of solution water activity, due to the addition of sucrose, glycerol ethylene glycol, and betaine, favors drug binding to the strong binding sites on DNA by increasing both the apparent binding affinity Delta G, and the number of DNA base pairs apparently occupied by the bound drug n(bp/actD). These binding parameters vary linearly with the logarithm of the molar fraction of water in solution log(X-w), which indicates the contribution of water binding to the energetic of the reaction. It is demonstrated that the hydration change measured upon binding increases proportionally to the apparent size of the binding site n(bp/uctD). This indicates that n(bp/actD) measured from the Scatchard plod is a measure of the size of the DNA molecule changing conformation due to ligand binding. We also find that the contribution of DNA deformation, gauged by n(bp/act) to the total free energy of binding Delta G, is given by Delta G = Delta G(local) + n(bp/actD) x delta G(DNA), where Delta G(local), = -8020 +/- 51 cal/mol of actD bound and delta G(DNa) = -24.1 +/- 1.7cal/mol of base pair at 25 degrees C. We interpret Delta G(local), as the energetic contribution due to the direct interactions of actD with the actual tetranucleotide binding site, and it n(bp/actB) X delta G(DNA) as that due to change inconformation, induced by binding, of it n(bp/actD) DNA base pairs flanking the local site. This interpretation is supported by the agreement found between the value of delta G(DNA) and the torsional free energy change measured independently. We conclude suggesting an allosteric model for ligand binding to DNA, such that the increase in binding affinity is achieved by increasing the relaxation of the unfavorable free energy of binding storage at the local site through a larger number of DNA base pairs. The new aspect on this model is that the size of the complex is not fixed but determined by solutions conditions, such as water activity, which modulate the energetic barrier to change helix conformation. These results may suggest that long-range allosteric transitions of duplex DNA are involved in the inhibition of RNA synthesis by actD, and more generally, in the regulation of transcription. (C) 2000 John Wiley & Sons, Inc.

Effect of non-steroidal anti-inflammatory drugs (NSAID) on the histamine release induced by compound 48/80 and cardiac anaphylaxis in guinea-pig isolated heart

Histamine release from guinea pig heart treated with compound 48/80 was potentiated by the cyclooxygenase inhibitors indomethacin and piroxicam but not by aspirin or phenylbutazone. This differential effect suggests that the potentiation is not merely due to an inhibition of prostaglandin synthesis. Piroxicam potentiated the histamine release induced by cardiac anaphylaxis whereas indomethacin reduced this effect. The SRS-A antagonist FPL 55712 inhibited histamine release induced by cardiac anaphylaxis, but not that evoked by compound 48/80, and also prevented the potentiation due to indomethacin and piroxicam. In total, these data suggest that the potentiation of histamine release by piroxicam and indomethacin is probably due to a diversion of arachidonic acid metabolism from the cyclooxygenase to the lipoxygenase pathways. The resulting lipoxygenase products may then regulate histamine release, with the secretion due to antigen being more sensitive to such modulation than that evoked by compound 48/80.

Agents that inhibit histamine release: A review

It is well known that histamine is found in high concentration in mast cell granules(1). The histamine content of these granules may be released to the extracellular space if an appropriate stimulus is provided(2). Besides histamine, other preformed active substances like enzymes, chemotatic factors and proteoglycans, as well as newly generated mediators like eicosanoids, platelet activating factor and adenosine are released during the secretion process of mast cells(3). The activation of mast cell degranulation has been associated with a number of pathologic disorders, most frequently, diseases derived from the atopic state(4). It is now evident that mast cells are the primary effector cells in the early reaction in both allergic and non-allergic asthma(5,6), although some authors doubt that the late reaction of asthma is a mast cell dependent event(6). Other studies point towards basophils as cellular elements involved in the secondary phase of inflammation in allergic diseases(7). Secretion would depend on a histamine releasing factor, and on the presence of IgE on the basophil's surface(8). There is also evidence suggesting involvement of mast cells in some non-allergic inflammatory processes like arthritis(9). The pharmacological management of these diseases basically consists in the use of methylxantines, beta 2-adrenergic agonists, glucocorticoids, sodium cromoglycate-like drugs, anticholinergic and antihistaminic H 1 antagonists(10). Their therapeutic effects include bronchodilatation, receptor and physiological antagonism, prevention of inflammatory responses induced by secondary cells, and finally, inhibition of mast cell activation(11). This review is concerned with compounds having inhibitory action on mast cell activation, and their possible importance on the pathophysiology of mast cell-related diseases.

Histamine release induced by glucose (mannose)-specific lectins isolated from Brazilian beans. Comparison with concanavalin A

The histamine releasing properties of glucose (mannose)-specific lectins isolated from Brazilian beans was examined. The Canavalia brasiliensis, Dioclea rostrata, and Dioclea virgata lectins induced histamine release in rat peritoneal mast cells similar to concanavalin A. Less potency and efficacy was observed for Canavalia maritima, Dioclea guianensis, and Dioclea violacea while very low activities were seen for the lectins from Dioclea grandiflora, Canavalia bonariensis, and Cratylia floribunda. The histamine releasing effect was quenched by higher doses of D. virgata lectin similar to what was reported for concanavalin A. This effect was abrogated by increasing the concentration of calcium in the incubating medium. As these above proteins have sites that bind calcium, higher doses of the lectins might withdraw the calcium which is essential for the mast cell secretion.

Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia

The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 12 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 12 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1-2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration increased and haematocrit decreased during halothane anaesthesia. The concentrations of met-enkephalin, dynorphin and catecholamines did not change and those of β-endorphin, adrenocorticotrophin, arginine vasopressin and cortisol increased during halothane anaesthesia. Halothane appeared to be a major stimulus to pituitary adrenocortical activation because the adrenocortical secretion was proportional to the amount of halothane inhaled. β-endorphin increased proportionally more than adrenocorticotrophin and their plasma concentrations were not correlated, suggesting that they have independent secretion mechanisms.

Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake and release in rat striatal slices

Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic transmission through inhibition of dopamine uptake and enhanced release of the transmitter. We evaluated the changes in the inhibition of uptake and the release of striatal [ 3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200-250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were used. In the behavioral experiments the rats (N = 8 for each group) received FCF (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the duration of activity (sniffing, rearing and locomotion) was recorded for 120 min. The basal motor activity was higher (28.6 ± 4.2 vs 8.4 ± 3.5 s) after saline administration at 21:00 h than at 9:00 h. FCF at a single dose significantly enhanced the basal motor activity (38.3 ± 4.5 vs 8.4 ± 3.5 s) and increased the duration of exploratory activity (38.3 ± 4.5 vs 32.1 ± 4.6 s) during the light, but not the dark phase. Two other groups of rats (N = 6 for each group) were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine uptake and relase assays. The inhibition of uptake and release of [ 3H]-dopamine were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the release properties of FCF undergo daily variation. These data suggest that the circadian time-dependent effects of FCF might be related to a higher susceptibility of dopamine presynaptic terminals to the action of FCF during the light phase which corresponds to the rats' resting period.

Release of formaldehyde by 4 endodontic sealers

Objective. The purpose of this study was to evaluate the release of formaldehyde by some root canal filling materials. Study design. Two older endodontic sealers, AH 26 and Endomethasone, and 2 recently available sealers, AH Plus and Top Seal, were analyzed. Infrared and electronic spectroscopy were used to determine formaldehyde content after set of the materials. Results. Analysis showed that the AH 26 and Endomethasone sealers released formaldehyde. Although the AH Plus and Top Seal sealers have similar chemical composition, they released formaldehyde in a minimal concentration. Conclusions. The AH 26 and Endomethasone sealers released formaldehyde after setting; however, a minimum release was observed for the AH Plus and Top Seal sealers. Copyright © 1999 by Mosby, Inc.

Efficacy and total release interval of mating disruption pheromone on the control of pink bollworm - Pectinophora Gossypiella - in cotton under field conditions in Brazil

This experiment was developed in order to evaluation the efficiency of pheromone to control the pink bollworm and the total time of its release in cotton field. The experiment was installed in field conditions, in Chapadao do Sul/SP/Brazil, from January to April, 1998. The treatments consisted of 2 areas, being one of 30ha, where it was applied the pheromone and another of 10ha that was chosen as control area and did not receive pheromone. In the treated area, the laboratory synthesized sex pheromone (PB-Rope) was used thought of dispensers that allowed the slow and gradual release of the active substance. A total of 250 dispenser per hectare were evenly hand distributed in the area. The dispensers were wrapped around the plants. Both areas (treated area and untreated area) were monitored by delta trap. For evaluation of the boll damage, the treatment area was divided into 4 sub-areas. Twenty five green bolls were collected at random from each sub-area at 48 and 65 days after pheromone treatment. Bolls were cracked open by hand, and number of the bolls with symptoms of pink bollworm attacks was recorded. For evaluation of the productivity four areas were demarcated in each treatment, where all fibers and seeds harvested were weighted. Release rate of pheromone from dispenser was evaluated through of the weigh of the dispensers. Were marked and weighed in analytic scale, 20 dispensers contend the pheromone, being placed 10 dispensers under the cotton plants in treated area and other 10 dispensers in an open area. To every 15 days the dispensers were retired and weighed in analytic scale and soon after put back in the field in the same places. The results showed that only one application of mating disrupt pheromone, used in a dosage of 250 dispenser/ha, reached 80% of control for pink bollworm. the release period of pheromone from dispenser, after the application, was 120 days.