Cadaveric Evaluation of Load to Failure in Canine Gingiva Apposed With Varied Suture Patterns Using Poliglecaprone 25

The purpose of the study was to determine the effect of suture pattern and repair length on the load to failure in an ex vivo canine gingival model. Healthy mandibular gingiva and mucosa were harvested from fresh cadavers euthanized for purposes unrelated to the study. Samples were randomly assigned by length and pattern. Lingual and buccal free gingival margins were apposed using a simple interrupted (SI), cruciate (XT), simple continuous (SC), or unidirectional knotless continuous barbed suture (SF) closure technique with USP 4-0 poliglecaprone 25i, ii applied over 2 lengths (3 cm and 6 cm). A custom template was used to ensure uniform suture bite application. Surgical time was recorded. Using a soft tissue mechanical testing frame, samples were tensioned to failure. Testing was video recorded and reviewed in conjunction with the tension trace data for tension at initial failure (Tfail) and maximum tension sustained (Tmax). Two factor ANOVA by length and pattern was performed followed by individual one way T-tests. Statistically significant findings were XT-SC-SF patterns were quicker to perform than SI. SF was more likely to fail by suture breakage than tissue tearing, and SF withstood less tension at the 3 cm length than SI-XT-SC. No significant difference was detected in Tmax or Tfail between SI and SC or XT. The study demonstrates that SC and XT are comparable to SI in tension resistance and faster to perform suggesting that SC and XT could replace SI for extraction site closure although further in vivo testing is required.

Dissolution Testing of Nicotine Release from OTDN Pouches: Product Characterization and Product-to-Product Comparison

In recent years, oral tobacco-derived nicotine (OTDN) pouches have emerged as a new oral tobacco product category. They are available in a variety of flavors and do not contain cut or ground tobacco leaf. The on!® nicotine pouches fall within this category of OTDN products and are currently marketed in seven (7) flavors with five (5) different nicotine levels. Evaluation of the nicotine release from these products is valuable for product assessment and product-to-product comparisons. In this work, we characterized the in vitro release profiles of nicotine from the 35 varieties of on!® nicotine pouches using a fit-for-purpose dissolution method, employing the U.S. Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4). The nicotine release profiles were compared using the FDA’s Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms. The cumulative release profiles of nicotine show a dose dependent response for all nicotine levels. The on!® nicotine pouches exhibit equivalent percent nicotine release rates for each flavor variant across all nicotine levels. Furthermore, the nicotine release profiles from on!® nicotine pouches were compared to a variety of other commercially available OTDN pouches and traditional pouched smokeless tobacco products. The percent nicotine release rates were found to be dependent on the product characteristics, showing similarities and differences in the nicotine release profiles between the on!® nicotine pouches and other compared products.

A one parameter family of Calabi-Yau manifolds with attractor points of rank two

In the process of studying the ζ-function for one parameter families of Calabi-Yau manifolds we have been led to a manifold, first studied by Verrill, for which the quartic numerator of the ζ-function factorises into two quadrics remarkably often. Among these factorisations, we find persistent factorisations; these are determined by a parameter that satisfies an algebraic equation with coefficients in ℚ, so independent of any particular prime. Such factorisations are expected to be modular with each quadratic factor associated to a modular form. If the parameter is defined over ℚ this modularity is assured by the proof of the Serre Conjecture. We identify three values of the parameter that give rise to persistent factorisations, one of which is defined over ℚ, and identify, for all three cases, the associated modular groups. We note that these factorisations are due a splitting of Hodge structure and that these special values of the parameter are rank two attractor points in the sense of IIB supergravity. To our knowledge, these points provide the first explicit examples of non-singular, non-rigid rank two attractor points for Calabi-Yau manifolds of full SU(3) holonomy. The values of the periods and their covariant derivatives, at the attractor points, are identified in terms of critical values of the L-functions of the modular groups. Thus the critical L-values enter into the calculation of physical quantities such as the area of the black hole in the 4D spacetime. In our search for additional rank two attractor points, we perform a statistical analysis of the numerator of the ζ-function and are led to conjecture that the coefficients in this polynomial are distributed according to the statistics of random USp(4) matrices.

Polycomplex Carrier for Buccal Mucoadhesion Delivery of Metronidazole

Introduction. One of the well-known requirements for buccal drug delivery systems is the demonstration of mucoadhesive properties of the carrier, ensuring retention on the mucosa for a long time with the gradual release of the included drug. It should be noted that one of the advantages of buccal systems compared with oral ones is the absence of the «first pass effect» through the liver.Aim. To carry out a physicochemical and pharmaceutical research of the interpolyelectrolyte complex (IPEC), obtained on the basis of pharmaceutically acceptable polymers – Eudragit® EPO and Noveon® AA-1, in comparison with the physical mixture and individual polymers, as a mucoadhesive delivery system of metronidazole for the treatment of periodontal diseases.Materials and methods. Obtained on the basis of a pair of pharmaceutical polymers (Eudragit® EPO and Noveon® AA-1), two IPEC samples were characterized by elemental analysis, FTIR spectroscopy, and modulated temperature differential scanning calorimetry (mDSC) in comparison with individual polymers and their physical mixtures. The study of swelling ability, bioadhesion and release was carried out in a medium simulating artificial salivary fluid (pH 7.0) at a temperature of 37 ± 0.1 °C. Mucoadhesion of polymer samples and IPEC was studied using a TA.XTplus texture analyzer (Stable Micro Systems, UK). The release of metronidazole (MD) from matrices based on the developed IPEC was studied on a CE 7Smart USP 4 apparatus (Sotax, Switzerland) using the Flow Trough Cell method at a speed a flow of 20 ml/min in an open cycle within 5 hours. The amount of released MD was estimated by UV spectrophotometry on a Lambda 25 instrument (PerkinElmer, USA) at a wavelength of 319 nm.Results and discussion. As a result of studies on the physicochemical and pharmaceutical properties, there was selected the optimal composition of a polycomplex carrier (IPEC 2) based on Eudragit® EPO and Noveon® AA-1, which is characterized by the required bioadhesive properties and the ability of providing controlled release of drug from the tablet matrix (with weight ratio MD/IPEC-2 1:0.5) in conditions mimicking oral cavity environment, which provides the necessary mode of buccal delivery of metronidazole in accordance with Fick's law of diffusion.Conclusion. IPEC 2 is a perspective for use as carrier for buccal controlled delivery of metronidazole.

$$dS_5$$ vacua from matter-coupled 5D $$N=4$$ gauged supergravity

We study $$dS_5$$dS5 vacua within matter-coupled $$N=4$$N=4 gauged supergravity in five dimensions using the embedding tensor formalism. With a simple ansatz for solving the extremization and positivity of the scalar potential, we derive a set of conditions for the gauged supergravity to admit $$dS_5$$dS5 as maximally symmetric background solutions. The results provide a new approach for finding $$dS_5$$dS5 vacua in five-dimensional $$N=4$$N=4 gauged supergravity and explain a number of notable features pointed out in previous works. These conditions also determine the form of the gauge groups to be $$SO(1,1)\times G_{\text {nc}}$$SO(1,1)×Gnc with $$G_{\text {nc}}$$Gnc being a non-abelian non-compact group. In general, $$G_{\text {nc}}$$Gnc can be a product of SO(1, 2) and a smaller non-compact group $${G^{\prime }}_{{\text {nc}}}$$G′nc together with (possibly) a compact group. The SO(1, 1) factor is gauged by one of the six graviphotons, that is singlet under $$SO(5)\sim USp(4)$$SO(5)∼USp(4) R-symmetry. The compact parts of SO(1, 2) and $${G^{\prime }}_{{\text {nc}}}$$G′nc are gauged by vector fields from the gravity and vector multiplets, respectively. In addition, we explicitly study $$dS_5$$dS5 vacua for a number of gauge groups and compute scalar masses at the vacua. As in the four-dimensional $$N=4$$N=4 gauged supergravity, all the $$dS_5$$dS5 vacua identified here are unstable.

IN VITRO EQUIVALENCE STUDY OF DIFFERENT DOSES OF CARBAMAZEPINE REFERENCE TABLETS USING USP APPARATUSES 2 AND 4

Objective: To perform an in vitro equivalence study of two doses of carbamazepine reference tablets sold in the local market under hydrodynamic conditions of USP Apparatus 4, a dissolution apparatus that better simulates the human gastrointestinal tract. Results were compared with dissolution official conditions using USP Apparatus 2. Methods: Dissolution profiles of both formulations were carried out with an automated USP Apparatus 2 at 75 rpm and 900 ml of dissolution medium. USP Apparatus 4 with laminar flow at 16 ml/min and 22.6 mm cells were used. 1% lauryl sulfate aqueous solution at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 285 nm was carried out during 60 min. Dissolution profiles were compared with model-independent and-dependent approaches. Results: When comparing dissolution profiles of low vs. high dose similar profiles were found (f2>50) in each dissolution apparatus, however, when the same dose was compared, USP 2 vs. USP 4, opposite results were obtained. Comparison of mean dissolution time and dissolution efficiency data corroborates these results. Weibull function was the best mathematical model that described the in vitro dissolution performance of carbamazepine. No significant differences were found in Td values (low vs. high dose) but opposite results were also found with USP 2 vs. USP 4. Conclusion: Equivalent dissolution performance of two doses of carbamazepine reference tablets were found in each USP dissolution apparatus. The main problem identified in this comparative study is the low dissolution rate and extent found with USP Apparatus 4. More research on this field is necessary for all available doses of reference drug products since the quality of generic formulations depends on the quality of references.

Mutação R337H no gene TP53, frequente no Sul e Sudeste do Brasil, não parece ser suficiente como causa de câncer em crianças e adultos

Nesta Edição Temática da “História do Controle do Câncer no Brasil”, registramos o progresso alcançado até o momento no entendimento epidemiológico e vigilância dos tumores adrenocorticais (TCA ) no Estado do Paraná. Esses resultados foram apresentados no Congresso deEndocrinologia Pediátrica realizado em Curitiba, no ano de 2000, e um ano mais tarde, por meio da publicação do mesmo grupo3, confirmada por endocrinologistas da Universidade de São Paulo (USP)4.