Experimental periodontal disease treatment by subgingival irrigation with tetracycline hydrochloride in rats

Objective: The aim of this study was to compare subgingival irrigation with tetracycline hydrochloride (TTC-HCL) as adjunctive treatment to scaling and root planning (SRP) on induced periodontitis in rats. Material and Methods: In 60 rats, periodontal disease was ligature-induced at the mandibular left first molar. After 7 days, the ligature was removed and all animals were submitted to SRP, and divided into 2 groups according to the following treatment: C (n=30) - subgingival irrigation with 1 mL of saline; T (n=30) - subgingival irrigation with 1 mL of TTC-HCL (50 mg/mL). Ten animals in each group were euthanized at 7, 15 and 30 days posttreatment. The histometric values were statistically analyzed (p<0.05). Results: In the histometric analysis, at 7, 15 and 30 days, Group T (0.72+/-0.05 mm(2), 0.57+/-0.14 mm(2), 0.62+/-0.07 mm(2)), showed less bone loss (p<0.05) than Group C (1.35+/-0.25 mm(2); 1.40+/-0.31 mm(2); 1.29+/-0.27 mm(2)), respectively. Conclusions: Subgingival irrigation with TTC-HCL was an effective adjunctive treatment for periodontal disease induced in rats.

Smear layer removal and collagen fiber exposure using tetracycline hydrochloride conditioning

Aim: Smear layer removal and collagen fiber exposure may improve periodontal treatment and regeneration. This in vitro study assessed smear layer removal and collagen fiber exposure after tetracycline hydrochloride (TTC) application on root surfaces using scanning electron microscopy (SEM). Methods and Materials: Root cementum was removed with diamond burs followed by scaling and root planning. Four hundred fifty samples were divided into ten groups: a control (saline application) and nine different TTC concentrations were applied at doses of 10, 25, 50, 75, 100, 125, 150, 200, and 250 mg/ml. The TTC application was performed in all groups in three different ways (passive, brushing, and burnishing) and at three different periods of conditioning (1, 2, and 3 minutes). A previously trained, calibrated, and blind examiner evaluated photomicrographs of the samples using Sampaio's index (2005). Statistical analysis was performed using the Kruskal-Wallis' and Dunn's tests. Results: The concentrations of 50 mg/mL and 75 mg/mL applied by burnishing were the most effective in smear layer removal and collagen fiber exposure. Both the passive mode of application (p=0.0001) and 1 minute period of application (p=0.002) were the least effective. Conclusions: The concentrations of 50 mg/mL and 75 mg/mL applied by burnishing during 2 or 3 minutes were the most effective. Clinical Significance: These parameters may be applied in periodontal procedures involving TTC root conditioning to optimize results.

Formulation and characterisation of tetracycline-containing bioadhesive polymer networks designed for the treatment of periodontal disease.

This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w) may be useful for the treatment of periodontal disease.

Healing of dehiscence defects following root surface demineralization with tetracycline: A histologic study in monkeys

Background: the purpose of this study was to histologically evaluate the healing of experimental dehiscence defects after surface demineralization with tetracycline hydrochloride.Methods: Six adult male monkeys (Cebus apella) were used in this study. Dehiscence defects were surgically created on the buccal aspect of the mandibular lateral incisors in all animals. The root surfaces were debrided and planed. In a split-mouth design, a 10% tetracycline hydrochloride solution was applied to one tooth for 4 minutes (T group), followed by irrigation with saline. The contralateral tooth served as a control (C group). The flaps were repositioned and sutured. The animals were sacrificed at 6 months postoperatively and histological sections were processed. Computer-assisted histomorphometric analysis was used to evaluate the formation of new cementum, new bone, new connective tissue attachment, and length of the epithelium (junctional and sulcular).Results: Bone regeneration was similar in both groups (1.5 +/- 0.3 mm for the T group and 1.5 +/- 0.6 mm for the C group). The C group showed more new cementum than the T group (2.3 +/- 0.3 mm versus 2.2 +/- 0.3 mm) as well as a longer epithelium (1.0 +/- 0.3 mm versus 0.9 +/- 0.2 mm). The T group presented more new connective tissue attachment (3.1 +/- 0.2 mm) than the C group (2.9 +/- 0.6 mm). However, no statistically significant differences were detected between the two groups.Conclusions: the amount of new attachment was similar in both groups. Root conditioning with 10% tetracycline solution did not produce any additional new attachment in comparison to the controls.

Pharmacokinetics of tetracycline in plasma, synovial fluid and milk using single intravenous and single intravenous regional doses in dairy cattle with papillomatous digital dermatitis

The purpose of this study was to compare the pharmacokinetics of tetracycline in plasma, synovial fluid, and milk following either a single systemic intravenous (i.v.) injection or a single i.v. regional antibiosis (IVRA) administration of tetracycline hydrochloride to dairy cattle with papillomatous digital dermatitis (PDD). To this end, plasma and synovial fluid tetracycline concentrations were compared with the minimal inhibitory concentration (MIC) values of the major bacteria, which are known to cause digital diseases and thus assess its efficacy in PDD. Residual tetracycline concentrations in milk from cows treated by both methods were also determined. Twelve Holstein cows with various stages of PDD were randomly assigned to two groups of six animals. Group 1 received a single systemic i.v. injection of 10 mg/kg of tetracycline hydrochloride. Group 2 received 1000 mg of tetracycline hydrochloride by IVRA of the affected limb. Blood, synovial fluid and milk samples were taken prior to tetracycline administration (time 0 control), and then at 22, 45 and 82 min, and 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h following drug administration. Tetracycline concentrations were determined by high-performance liquid chromatography. Mean tetracycline plasma and milk concentrations in Group 1 were higher than Group 2. The opposite was observed for synovial fluid concentrations. Group 2 synovial fluid concentrations were higher than the MIC value over 24 h for the bacteria most frequently responsible for claw disease. Compared with i.v. administration, IVRA administration of tetracycline produced very high synovial fluid and low plasma and milk concentrations.

Experimental periodontal disease treatment by subgingigval irrigation with tetracycline hidrochloride in rats

Objective: The aim of this study was to compare subgingival irrigation with tetracycline hydrochloride (TTC-HCL) as adjunctive treatment to scaling and root planning (SRP) on induced periodontitis in rats. Material and Methods: In 60 rats, periodontal disease was ligature-induced at the mandibular left first molar. After 7 days, the ligature was removed and all animals were submitted to SRP, and divided into 2 groups according to the following treatment: C (n=30) – subgingival irrigation with 1 mL of saline; T (n=30) – subgingival irrigation with 1 mL of TTC-HCL (50 mg/mL). Ten animals in each group were euthanized at 7, 15 and 30 days posttreatment. The histometric values were statistically analyzed (p<0.05). Results: In the histometric analysis, at 7, 15 and 30 days, Group T (0.72±0.05 mm2, 0.57±0.14 mm2, 0.62±0.07 mm2), showed less bone loss (p<0.05) than Group C (1.35±0.25 mm2; 1.40±0.31 mm2; 1.29±0.27 mm2), respectively. Conclusions: Subgingival irrigation with TTC-HCL was an effective adjunctive treatment for periodontal disease induced in rats.

Validation of daily growth increments and estimation of growth rates of larval and early juvenile black skipjack, Euthynnus lineatus, using otoliths

ENGLISH: Increments in otoliths (sagittae) were examined, using light and scanning electron microscopy, to determine ages and estimate growth rates of larval and early-juvenile black skipjack, Euthynnus lineatus. Larvae and juveniles were collected between 1987 and 1989 from coastal waters of Panama in the eastern Pacific Ocean. Results from a laboratory experiment indicated that immersion for 6 and 12 hours in a 200 mg/L solution of tetracycline hydrochloride adequately marks otoliths and that increments are formed daily in the sagittae of postflexion larvae and early juveniles. Further, survival rates of tetracycline-treated fish were not significantly different from those of control fish. Growth rates were derived from length-age relationships of 218 field-collected specimens ranging in size from 5.7 to 20.3 mm SL. A growth rate of 0.70 mm/d was estimated from the weighted regression of standard length on age for all specimens. This rate lies within the range reported for larvae and early juveniles of other species of subtropical and tropical scombrids. Growth rates of postflexion larvae and early juveniles were not significantly different between the rainy season in July-August 1988 and the dry, upwelling season in January-February 1989. Growth was, however, significantly more variable for older individuals in July-August than in January-February, and may correspond, in part, to seasonal patchiness of prey. The growth rates of the otoliths relative to fish length were also not significantly different between seasons; however, the otoliths were larger relative to the lengths of fish collected in the rainy season, which may reflect slower growth during earlier larval stages. SPANISH: Se examinaron incrementos en otolitos (ságitas), usando microscopia de luz y de barrido electrónico, a fin de determinar la edad y estimar las tasas de crecimiento de barriletes negros, Euthynnus lineatus, larvales y juveniles tempranos. Entre 1987 y 1989 se capturaron larvas y juveniles en las aguas costeras de Panamá en el Océano Pacífico oriental. Los resultados de un experimento de laboratorio indicaron que una inmersión de 6 a 12 horas de duración en una solución de 200 mg/L de hidrocloro de tetraciclina marca los otolitos adecuadamente y que los incrementos se forman a diario en las ságitas de larvas en postflexión y juveniles tempranos. Además, las tasas de supervivencia de los peces tratados con tetraciclina no fueron significativamente diferentes a aquellas de los peces de control. Se calcularon las tasas de crecimiento a partir de las relaciones de talla-edad de 218 especímenes de TE entre 5.7 y 20.3 mm capturados en el mar. Se estimó.una tasa de crecimiento de 0.70 mm/día a partir de la regresión ponderada de talla estándar sobre edad para todos los especímenes. Esta tasa cae dentro del rango reportado para larvas y juveniles tempranos de otras especies de escómbridos subtropicales y tropicales. Las tasas de crecimiento de larvas en postflexión y juveniles tempranos no fueron significativamente diferentes entre la temporada de lluvias en julio-agosto de 1988 y la temporada de sequía y afloramiento en enero-febrero de 1989. Sin emoargo, el crecimiento fue significativamente más variable para los individuos de mayor edad en julio-agosto que en enero-febrero, y quizás corresponda parcialmente a la irregularidad temporal de la abundancia de presas. Las tasas de crecimiento de los otolitos en relación a la talla de los peces tampoco fueron significativamente diferentes entre temporadas; sin embargo, los otolitos eran más grandes en relación a la talla en peces capturados en la temporada de lluvias, lo cual podría reflejar crecimiento más lento durante las etapas larvales más tempranas. (PDF contains 42 pages.)

Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

Despite their widespread use, there is a paucity of information concerning the effect of storage on the rheological properties of pharmaceutical gels that contain organic and inorganic additives. Therefore, this study examined the effect of storage (1 month at either 4 or 37 degrees C) on the rheological and mechanical properties of gels composed of either hydroxypropylmethylcellulose (3-5% w/w, HPMC) or hydroxyethylcellulose (3-5% w/w, HEC) and containing or devoid of dispersed organic (tetracycline hydrochloride 2% w/w) or inorganic (iron oxide 0.1% w/w) agents. The mechanical properties were measured using texture profile analysis whereas the rheological properties were analyzed using continuous shear rheometry and modeled using the Power Law model. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing polymer concentration (3-5% w/w) significantly increased the consistency, hardness, compressibility, and adhesiveness of the formulations due to increased polymer chain entanglement. Following storage (I month at 4 and 37 degrees C) the consistency and mechanical properties of additive free HPMC gets (but not HEC gels) increased, due to the time-dependent development of polymer chain entanglements. Incorporation of tetracycline hydrochloride significantly decreased and increased the rheological and mechanical properties of HPMC and HEC gels, respectively. Conversely, the incorporation of iron oxide did not affect these properties. Following storage, the rheological and mechanical properties of HPMC and HEC formulations were markedly compromised. This effect was greater following storage at 37 than at 4 degrees C and, additionally, greater in the presence of tetracycline hydrochloride than iron oxide. It is suggested that the loss of rheological/mechanical structure was due to chain depolymerization, facilitated by the redox properties of tetracycline hydrochloride and iron oxide. These observations have direct implications for the design and formulation of gels containing an active pharmaceutical ingredient. (c) 2005 Wiley Periodicals, Inc.

Optimisation de la concentration en électrolytes au sein des matrices à base de HASCA pour la libération prolongée

Le sel sodique du carboxyméthylamidon à haute teneur en amylose, HASCA (Amylose 60%-amylopectine 40%), est un polymère hydrophile ionique utilisé pour obtenir des comprimés matriciels à libération prolongée. Il est caractérisé par la formation d'un hydrogel lors de la mise en contact avec le milieu de dissolution. La libération du principe actif (PA) à travers ce polymère est principalement contrôlée par la diffusion fickienne et la relaxation du réseau polymérique. De plus, la solubilité du PA est un facteur qui permet de moduler la libération, cependant, la solubilité d’un médicament dépend de la forme utilisée et du pH. Les bases ou les acides libres présentent une solubilité moins élevée que leurs sels. Nous proposons d’étudier l’effet d’une combinaison entre le sel et la forme acide ou le sel et la forme alcaline dans le même comprimé matriciel d’HASCA. Comme objectif de ce travail, nous étudions l’influence de la nature du polymère sur le profil de libération de PA dans un milieu aqueux en gradient de pH à cause de la nature des matrices à base d’HASCA caractérisées par la présence de groupement carboxyliques, ionisés ou non selon l’acidité du milieu de dissolution. Nous étudions également l’influence de la nature du PA (base libre ou son sel vs acide libre ou son sel) sur le profil de libération, ceci en sélectionnant des PAs modèles représentatifs de chaque catégorie. L’influence de changement de proportions entre la forme libre (acide ou base) et son sel sur le profil de libération est aussi investiguée. Pour ce, des comprimés à base de HASCA avec des proportions différentes de, soit le naproxène acide et le naproxène de sodium (PA acide et son sel), soit la tétracycline et le chlorhydrate de tétracycline (PA alcalin et son sel) ont été utilisés. Ceux-ci sont évalués lors des tests de dissolution dans un milieu simulant le milieu gastro-intestinal, selon les normes de l’USP (spectrophotométrie UV). Nous avons également menés des études de vitesse de dissolution intrinsèque sur les PAs purs, afin de déterminer leur solubilité et vitesse de libération dans les même pH de dissolution étudiés. Nous avons réussit d’obtenir des comprimés matriciels à base de HASCA convenables à être administrés une fois par jour en utilisant une combinaison du naproxène acide et son sel comme PA. Tandis que les résultats ont montré qu’en utilisant la tétracycline et son sel, les temps de libération étaient trop élevés pour permettre la réalisation d’une formulation convenable pour une administration quotidienne unique

Estudos de adsorção de tetraciclina e cromoglicato em partículas de quitosana

Among the polymers that stand out most in recent decades, chitosan, a biopolymer with physico-chemical and biological promising properties has been the subject of a broad field of research. Chitosan comes as a great choice in the field of adsorption, due to their adsorbents properties, low cost and abundance. The presence of amino groups in its chain govern the majority of their properties and define which application a sample of chitosan may be used, so it is essential to determine their average degree of deacetylation. In this work we developed kinetic and equilibrium studies to monitor and characterize the adsorption process of two drugs, tetracycline hydrochloride and sodium cromoglycate, in chitosan particles. Kinetic models and the adsorption isotherms were applied to the experimental data. For both studies, the zeta potential analyzes were also performed. The adsorption of each drug showed distinct aspects. Through the studies developed in this work was possible to describe a kinetic model for the adsorption of tetracycline on chitosan particles, thus demonstrating that it can be described by two kinetics of adsorption, one for protonated tetracycline and another one for unprotonated tetracycline. In the adsorption of sodium cromoglycate on chitosan particles, equilibrium studies were developed at different temperatures, allowing the determination of thermodynamic parameters

Comparative analysis of root surface smear layer removal by different etching modalities or erbium:yttrium-aluminum-garnet laser irradiation. A scanning electron microscopy study

The purpose of this study was to evaluate the effect of erbium:yttrium-aluminum-garnet (Er:YAG) laser (2.94 mu m) irradiation on the removal of root surface smear layer of extracted human teeth and to compare its efficacy with that of citric acid, ethylenediamine tetra-acetic acid (EDTA), or a gel containing a mixture of tetracycline hydrochloride (HCl) and citric acid, using scanning electron microscopy (SEM). Thirty human dentin specimens were randomly divided into six groups: G1 (control group), irrigated with 10 ml of physiologic saline solution; G2, conditioned with 24% citric acid gel; G3, conditioned with 24% EDTA gel; G4, conditioned with a 50% citric acid and tetracycline gel; G5, irradiated with Er:YAG laser (47 mJ/10 Hz/5.8 J/cm(2)/pulse); G6, irradiated with Er:YAG laser (83 mJ/10 Hz/10.3 J/cm(2)/pulse). Electron micrographs were obtained and analyzed according to a rating system. Statistical analysis was conducted with Kruskal-Wallis and Mann-Whitney tests (P < 0.05). G1 was statistically different from all the other groups; no statistically significant differences were observed between the Er:YAG laser groups and those undergoing the other treatment modalities. When the two Er:YAG laser groups were compared, the fluency of G6 was statistically more effective in smear layer removal than the one used in G5 (Mann-Whitney test, P < 0.01). Root surfaces irradiated by Er:YAG laser had more irregular contours than those treated by chemical agents. It can be concluded that all treatment modalities were effective in smear layer removal. The results of our study suggest that the Er:YAG laser can be safely used to condition diseased root surfaces effectively. Furthermore, the effect of Er:YAG laser irradiation on root surfaces should be evaluated in vivo so that its potential to enhance the healing of periodontal tissues can be assessed.

Regeneration of class III furcation defects with basic fibroblast growth factor (b-FGF) associated with GTR. A descriptive and histometric study in dogs

Background: the poor predictability of periodontal regenerative treatment of Class III furcation defects stimulates the study of alternatives to improve its results, such as the use of polypeptide growth factors. The objective of this study was to evaluate, both histologically and histometrically, the effects of topical application of basic fibroblast growth factor (b-FGF) associated with guided tissue regeneration (GTR) in the treatment of Class III defects surgically induced in dogs.Methods: All second and fourth premolars of 5 mongrel dogs were used and randomly assigned to one of three treatment groups: group 1 (control), treated with scaling and root planing, tetracycline hydrochloride (125 mg/ml) conditioning, and GTR with a collagen membrane; group 2, same treatment as group 1 plus 0.5 mg of b-FGF; group 3, same treatment as group 1 plus 1.0 mg of b-FGF. After a 90-day healing period, routine histologic processing and staining with hematoxylin and eosin and Masson trichrome were performed.Results: the descriptive analysis indicated better regenerative results in both groups treated with b-FGF while the histometric data, analyzed by means of analysis of variance (ANOVA), showed greater filling of the defects in group 2 in comparison to the defects in groups 3 and 1, respectively, which was represented by a smaller area of plaque-occupied space (P = 0.004) as well as a greater amount of newly formed cementum (P = 0.002).Conclusions: These results indicate that b-FGF, especially in smaller doses, may enhance the regenerative results in Class III furcation lesions, leading to greater filling of these defects with both mineralized and non-mineralized tissues.

Thermal decomposition of some chemotherapic substances

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

Influence of dental exposure to oral environment on smear layer removal and collagen exhibition after using different conditioning agents

Although in vitro studies have shown encouraging results for root surface conditioning with demineralizing agents, in vivo studies have failed to show its benefits in periodontal healing. This can be attributed to several factors, among which, the hypermineralization of dental surface. Therefore, this in vitro study compared, using scanning electron microscopy (SEM), the effect of root surface conditioning with different conditioners (1% and 25% citric acid, 24% EDTA and 50 mg/mL tetracycline hydrochloride) in impacted teeth and in teeth that had their roots exposed to the oral environment. One trained examiner assessed the SEM micrographs using a root surface modification index. There was a tendency of more root surface modification in the group of impacted teeth, suggesting that the degree of root mineralization influences its chemical demineralization.