Pharmacokinetic Profile of A New Diclofenac Prodrug without Gastroulcerogenic Effect

Gastrotoxicity is a major problem for long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). DICCIC (1-(2,6-dichlorophenyl)indolin-2-one) is a new diclofenac prodrug, which has proven anti-inflammatory activity without gastroulcerogenic effect. The aim of this work was to compare the pharmacokinetic profiles of diclofenac from DICCIC (7.6 mg/kg equivalent to 8.1 mg/kg diclofenac) and diclofenac (8.1 mg/kg) administration in Wistar rats weighing 250-300 g (n=20). The doses were calculated by interspecific allometric scaling based on the 2 mg/kg from diary human dose of diclofenac. Blood samples were collected in heparinized tubes via the femoral artery through the implanted catheter. The plasma was separated and quantitation was made in a HPLC system with a UV-Vis detector. The confidence limits of the bioanalytical method were appropriate for its application in a preclinical pharmacokinetic study. The AUC of diclofenac from DICCIC (53.7± 5.8 ug/mL.min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (885.9 ± 124,8 ug/mL.min). Terminal half-life of diclofenac from DICCIC (50.1 ± 17.2 min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (247.4 ± 100.9 min). Still the parameters clearance and distribution volume were calculated for diclofenac from diclofenac, whose results were 9.2 ±1.2 mL/min.kg and 3.3 ±1.2 L/kg, respectively. The results of DICCIC from DICCIC administration were 108.9 ± 19.6 mL/min.kg and 7.8 ± 2.4 L/kg for clearance and distribution volume, respectively. The pharmacokinetic profile demonstrated that there was an increase in diclofenac elimination and a lower exposure to diclofenac with administration of DICCIC compared to diclofenac. © 2013 Bentham Science Publishers.

Seasonal metabolic depression, substrate utilisation and changes in scaling patterns during the first year cycle of tegu lizards (Tupinambis merianae)

The tegus increase in body mass after hatching until early autumn, when the energy intake becomes gradually reduced. Resting rates of oxygen consumption in winter drop to 20% of the values in the active season (Vo(2)=0.0636 ml g(-1) h(-1)) and are nearly temperature insensitive over the range of 17-25degreesC (Q(10)=1.55). During dormancy, plasma glucose levels are 60% lower than those in active animals, while total protein, total lipids and beta-hydroxybutyrate are elevated by 24%, 43% and 113%, respectively. In addition, a significant depletion of liver carbohydrate (50%) and of fat deposited in the visceral fat bodies (24%) and in the tail (25%) and a slight loss of skeletal muscle protein (14%) were measured halfway through the inactive period. Otherwise, glycogen content is increased 4-fold in the brain and 2.3-fold in the heart of dormant lizards, declining by the onset of arousal. During early arousal, the young tegus are still anorexic, although Vo(2) is significantly greater than winter rates. The fat deposits analysed are further reduced (62% and 45%, respectively) and there is a large decrease in tail muscle protein (50%) together with a significant increase in glycogen (2-3-fold) and an increase in plasma glucose (40%), which suggests a role for gluconeogenesis as a supplementary energy source in arousing animals. No change is detectable in citrate synthase activity, but beta-hydroxyacyl CoA dehydrogenase activities are strongly affected by season, reaching a Mold and 5-fold increase in the liver tissue of winter and arousing animals, respectively, and becoming reduced by half in skeletal muscle and heart of winter animals compared with late fall or spring active individuals. From hatching to late autumn, the increase of the fat body mass relatively to body mass is disproportionate (b=1.44), and the mass exponent changes significantly to close to 1.0 during the fasting period. The concomitant shift in the Vo(2) mass exponent in early autumn (b=0.75) to values significantly greater than 1.0 in late autumn and during winter dormancy indicates an allometric effect on the degree of metabolic depression related to the size of the fat stores and suggests greater energy conservation in the smaller young.

Allometric analysis of the ontogenetic variation and evolution of the skull in Caiman spix, 1825 (Crocodylia: Alligatoridae)

We studied ontogenetic variation in the shape of the skull among species of Caiman using principal component analysis. Comparison of multivariate allometric coefficients and ontogenetic trends between size and shape reveals that C. sclerops and C. yacare have similar ontogenetic processes, and they are more related to each other than either is to C. latirostris. Allometric relationships of the characters measured are similar in all species studied. The greater differences were in the width measurements, with higher coefficients in shape (second principal component) for C. latirostris, and length measurements with higher coefficients in shape for C. yacare and C. sclerops. The ontogenetic process leading to change in skull shape in the group seems to be plesiomorphic for elongation and derived for broadening. Statistical comparison of the ontogenetic trends with models of allometric heterochrony suggests that C. latirostris has diverged from the other species by a neotenic process, and that C. sclerops is separated from C. yacare by ontogenetic scaling (progenesis).

Intraspecific scaling of arterial blood pressure in the Burmese python

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

Allometric growth of two species of Ephemeroptera from Neotropical mountains streams

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Scaling-Up of Dental Pulp Stem Cells Isolated from Multiple Niches

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

Short-term clinical and immunologic effects of scaling and root planing with Er : YAG laser in chronic periodontitis

Background: Recently, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser has been used for periodontal therapy. This study compared Er:YAG laser irradiation (100 mJ/pulse, 10 Hz, 12.9 J/cm(2)) with or without conventional scaling and root planing (SRP) to SRP only for the treatment of periodontal pockets affected with chronic periodontitis.Methods: Twenty-one subjects with pockets from 5 to 9 mm in non-adjacent sites were studied. In a split-mouth design, each site was randomly allocated to a treatment group: SRP and laser (SRPL), laser only (L), SRP only (SRP), or no treatment (C). The plaque index (PI), gingival index (GI), bleeding on probing (BOP), and interleukin (IL)-1 beta levels in crevicular fluid were evaluated at baseline and at 12 and 30 days postoperatively, whereas probing depth (PD), gingival recession (GR), and clinical attachment level (CAL) were evaluated at baseline and 30 days after treatment. A statistical analysis was conducted (P<0.05).Results: Twelve days postoperatively, the PI decreased for SRPL and SRP groups (P<0.05); the GI increased for L, SRP, and C groups but decreased for the SRPL group (P<0.05); and BOP decreased for SRPL, L, and SRP groups (P<0.01). Thirty days postoperatively, BOP decreased for treated groups and was lower than the C group (P<0.05). PD decreased in treated groups (P<0.001), and differences were found between SRPL and C groups (P<0.05). CAL gain was significant only for the SRP group (P<0.01). GR increased for SRPL and L groups (P<0.05). No difference in IL-1 beta was detected among groups and periods.Conclusion: Er:YAG laser irradiation may be used as an adjunctive aid for the treatment of periodontal pockets, although a significant CAL gain was observed with SRP alone and not with laser treatment.

A scanning electron microscopy study of diseased root surfaces conditioned with EDTA gel plus Cetavlon after scaling and root planing

In the present investigation, a scanning electron microscopy analysis was performed to evaluate the effects of the topical application of ethylenediaminetetraacetic acid (EDTA) gel associated with Cetavlon (EDTAC) in removing the smear layer and exposing collagen fibers following root surface instrumentation. Twenty-eight teeth from adult humans, single rooted and scheduled for extraction due to periodontal reasons, were selected. Each tooth was submitted to manual (scaling and root planing) instrumentation alone or combined with ultrasonic instruments, with or without etching using a 24% EDTAC gel. Following extraction, specimens were processed and examined under a scanning electron microscope. A comparative morphological semi-quantitative analysis was performed; the intensity of the smear layer and the decalcification of cementum and dentinal surfaces were graded in 12 sets using an arbitrary scale ranging from 1 (area covered by a smear layer) to 4 (no smear layer). Root debridement with hand instruments alone or combined with ultrasonic instruments resulted in a similar smear layer covering the root surfaces. The smear layer was successfully removed from the surfaces treated with EDTAC, which exhibited numerous exposed dentinal tubules and collagen fibers. This study supports the hypothesis that manual instrumentation alone or instrumentation combined with ultrasonic instrumentation is unable to remove the smear layer, whereas the subsequent topical application of EDTAC gel effectively removes the smear layer, uncovers dentinal openings and exposes collagen fibers.

Clinical and Microbiologic Follow-Up Evaluations After Non-Surgical Periodontal Treatment With Erbium:YAG Laser and Scaling and Root Planing

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A comparison of the allometric growth in Uca leptodactyla (Crustacea : Brachyura : Ocypodidae) from two subtropical estuaries

The allometric growth of Uca leptodacyla from two distinct subtropical estuaries on the Brazilian coast was evaluated concerning its growth pattern and size at onset of sexual maturity. Females attained maturity at similar sizes in both sites (4.1 mm of carapace length in Indaia and 4.2 mm in Ubatumirim), while males differed slightly. They reached the size at sexual maturity of 5.3 mm of carapace length in Indaia and 4.6 mm in Ubatumirim. Growth pattern is Usually similar among crabs from distinct Sites while size at sexual maturity is frequently different. However, in the case of U. leptodacyla it did not occur, probably due to the strong habitat similarity and intrinsic features of this species.

Integrable aspects of the scaling q-state Potts models I: bound states and bootstrap closure

We discuss the q-state Potts models for q less than or equal to 4, in the scaling regimes close to their critical or tricritical points. Starting from the kink S-matrix elements proposed by Chim and Zamolodchikov, the bootstrap is closed for the scaling regions of all critical points, and for the tricritical points when 4 > q greater than or equal to 2. We also note a curious appearance of the extended last line of Freudenthal's magic square in connection with the Potts models. (C) 2003 Elsevier B.V. B.V. All rights reserved.

Scaling in few-body nuclear physics

The nuclear matter calculations with realistic nucleon-nucleon potentials present a general scaling between the nucleon-nucleus binding energy, the corresponding saturation density, and the triton binding energy. The Thomas-Efimov three-body effect implies in correlations among low-energy few-body and many-body observables. It is also well known that, by varying the short-range repulsion, keeping the two-nucleon information (deuteron and scattering) fixed, the four-nucleon and three-nucleon binding energies lie on a very narrow band known as a Tjon line. By looking for a universal scaling function connecting the proper scales of the few-body system with those of the many-body system, we suggest that the general nucleus-nucleon scaling mechanism is a manifestation of a universal few-body effect.

Integrable aspects of the scaling q-state Potts models II: finite-size effects

We continue our discussion of the q-state Potts models for q less than or equal to 4, in the scaling regimes close to their critical and tricritical points. In a previous paper, the spectrum and full S-matrix of the models on an infinite line were elucidated; here, we consider finite-size behaviour. TBA equations are proposed for all cases related to phi(21) and phi(12) perturbations of unitary minimal models. These are subjected to a variety of checks in the ultraviolet and infrared limits, and compared with results from a recently-proposed non-linear integral equation. A non-linear integral equation is also used to study the flows from tricritical to critical models, over the full range of q. Our results should also be of relevance to the study of the off-critical dilute A models in regimes 1 and 2. (C) 2003 Elsevier B.V. B.V. All rights reserved.

Scaling limit of weakly bound triatomic states

The usefulness of a scale-independent approach to identify Efimov states in three-body systems is shown by comparing such an approach with a realistic calculation in the case of three helium atoms. We show that the scaling limit is realized in practice in this case, and suggest its application to study other similar systems, including the case where two kinds of atoms are mixed. We also consider the observed large scattering length of the Rb-87 dimer to estimate the critical value of the ground-state energy of the corresponding trimer (greater than or equal to 1.5 mK), in order to allow for one Efimov state above the ground state.

Universal scaling in Bardeen-Cooper-Schrieffer superconductivity in two dimensions in non-s waves

The solutions of a renormalized BCS model are studied in two space dimensions for s, p and d waves for finite-range separable potentials. The gap parameter, the critical temperature T-c, the coherence length xi and the jump in specific heat at T-c as a function of the zero-temperature condensation energy exhibit universal scalings. In the weak-coupling limit, the present model yields a small xi and large T-c, appropriate for high-T-c cuprates. The specific heat, penetration depth and thermal conductivity as functions of temperature show universal scaling for p and d waves.