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We study a conformally coupled scalar-tensor theory with a quartic potential possessing local conformal symmetry up to a boundary term. We show that requiring the restoration of the full local conformal symmetry fixes the counterterms that render the on-shell action finite. The building block of the resulting action is a conformally covariant tensor which is constructed out of the metric and the scalar field and it has the same conformal weight as the Weyl tensor. This allows us to obtain the counterterms for the scalar-tensor sector in a closed form. The finiteness of the conformally complete version of the action is suggestive on the validity of the Conformal Renormalization prescription. We extend this theory by adding the Conformal Gravity action and also the Einstein-AdS action written in McDowell-Mansouri form. Even though the latter breaks the conformal symmetry, we find that the action is still renormalized provided a suitable falloff of the scalar field when considering asymptotically locally anti-de Sitter solutions. Black hole solutions in these theories are studied, for which the Hawking temperature and the partition function to first order in the saddle-point approximation are calculated, providing a concrete example of this renormalization scheme., 28 pages, accepted in PRD

Background Acute kidney injury (AKI) induced by renal ischemia/reperfusion (IR) is associated with enhanced production of reactive oxygen species in renal tissues. D-005, a lipid extract obtained from Acrocomia crispa fruit, has previously shown antioxidant effects. The aim of this work was to evaluate the effects of D-005 on renal IR-induced AKI in rats. Methods Rats were randomized into seven groups including a negative control group (vehicle) without AKI and six groups with renal IR-induced AKI as follows: a positive control (vehicle); D-005 treatment at 25, 100, 200, or 400 mg/kg; and dexamethasone at 3 mg/kg. All treatments were orally administered as single doses 1 hour before AKI induction. Biomarkers (serum creatinine, urea, and uric acid concentrations), oxidative variables, and histopathological AKI changes were evaluated in blood and kidney tissues. Results All D-005 doses protected against IR-induced AKI in rats by significantly decreasing biomarkers and histopathological AKI changes as assessed by reduced serum concentrations of creatinine, urea, and uric acid. In addition, all D-005 doses decreased tubular damage, as shown by fewer detached cells and casts in the tubular lumen. D-005 reversed oxidation disturbance markers by decreasing malondialdehyde and sulfhydryl group concentrations in plasma and in kidney homogenates and by increasing kidney catalase activity. Dexamethasone, the reference substance, protected against IR-induced AKI in rats by reducing biochemical and histological variables of renal damage in a similar manner. Conclusion Administration of single oral doses of D-005 markedly and significantly protected against renal IR-induced AKI, possibly due to its known antioxidant effects.

Background Colorectal cancer is one of the most common malignancies worldwide and is associated with high mortality rates. We previously reported that Xanthium strumarium L. induces mitotic arrest in proliferating cells, a process mediated by xanthatins. Hypothesis/Aim The aim of this work is to study if xanthatins, isolated from X. strumarium total extract, affect the proliferative capacity of CT26WT colon cancer cells and, in consequence, if tumor growth and proliferation of (lung) metastatic sites can also be arrested in vivo. Study design This study consisted of both in vitro and in vivo experiments involving the CT26WT cell line and a subcutaneous mouse model of colon cancer. In vitro cell cycle progression, in vivo tumoral growth and anti-metastatic activity were analyzed to investigate whether xanthatins of X. strumarium induce mitotic arrest in proliferating colorectal carcinoma. Results Our in vitro results show that X. strumarium, mediated by xanthatins, induces G2/M arrest and impair anaphase entrance. This leads to a significant induction of apoptotic and necrotic in CT26WT cells, demonstrating their significant anti-proliferative activity through interfering with the mitotic apparatus. Furthermore, our in vivoresults reveal that X. strumarium inhibits both tumor growth and metastasis progression. Conclusion X. strumarium antitumor activities are mainly mediated by xanthatins through inhibition of tumor growth and metastasis, inducing mitotic arrest and apoptosis in colon carcinoma cells. These findings further confirm the therapeutic potential of X. strumarium in colorectal cancer.

The aim of this study was to evaluate the effects of single oral doses of D-005 (a lipid extract obtained from the fruit oil of Acrocomia crispa) on LPS-induced acute lung injury (ALI) in mice. D-005 batch composition was: lauric (35.8%), oleic (28.4%), myristic (14.2%), palmitic (8.9%), stearic (3.3%), capric (1.9%), caprylic (1.2%), and palmitoleic (0.05%) acids, for a total content of fatty acids of 93.7%. D-005 (200 mg/kg) significantly reduced lung edema (LE) (≈ 28% inhibition) and Lung Weight/Body Weight ratio (LW/BW) (75.8% inhibition). D-005 (25, 50, 100 and 200 mg/kg) produced a significant reduction of Histological score (59.9, 56.1, 53.5 and 73.3% inhibition, respectively). Dexamethasone, as the reference drug, was effective in this experimental model. In conclusion, pretreatment with single oral doses of D-005 significantly prevented the LPS-induced ALI in mice.

The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering other long-term neuroprotective mechanisms of these drugs, we hypothesized that this combination might exert some synergistic effects on neuropathic pain linked with its possible ability to prevent Wallerian degeneration (WD). The effects of individual and fixed-ratio of 1:1 combinations of orally administered amitriptyline and paracetamol were assayed in the two phases of the formalin test and in the chronic constriction injury (CCI) model in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Amitriptyline, paracetamol, and fixed-ratio amitriptyline–paracetamol combinations produced dose-dependent antinociceptive effects mainly on the inflammatory tonic phase. Repeated doses of individual drugs and their combination decreased CCI-induced mechanical allodynia in a dose-dependent manner. ED30 (formalin) and ED50 (CCI) values were estimated for the individual drugs, and isobolograms were constructed. Theoretical ED30/50 values for the combination estimated from the isobolograms were 16.5 ± 3.9 mg/kg and 26.0 ± 7.2 mg/kg for the single and repeated doses in persistent and neuropathic pain models, respectively. These values were significantly higher than the actually observed ED30/50 values, which were 0.39 ± 0.1 mg/kg and 8.2 ± 0.8 mg/kg in each model, respectively, indicating a synergistic interaction. Remarkably, CCI-induced sciatic nerve WD-related histopathological changes were prevented by this combination compared to either drug administered alone.

We show that the phase space of three-dimensional gravity contains two layers of dualities: between diffeomorphisms and a notion of "dual diffeomorphisms" on the one hand, and between first order curvature and torsion on the other hand. This is most elegantly revealed and understood when studying the most general Lorentz-invariant first order theory in connection and triad variables, described by the so-called Mielke-Baekler Lagrangian. By analyzing the quasi-local symmetries of this theory in the covariant phase space formalism, we show that in each sector of the torsion/curvature duality there exists a well-defined notion of dual diffeomorphism, which furthermore follows uniquely from the Sugawara construction. Together with the usual diffeomorphisms, these duals form at finite distance, without any boundary conditions, and for any sign of the cosmological constant, a centreless double Virasoro algebra which in the flat case reduces to the BMS$_3$ algebra. These algebras can then be centrally-extended via the twisted Sugawara construction. This shows that the celebrated results about asymptotic symmetry algebras are actually generic features of three-dimensional gravity at any finite distance. They are however only revealed when working in first order connection and triad variables, and a priori inaccessible from Chern-Simons theory. As a bonus, we study the second order equations of motion of the Mielke-Baekler model, as well as the on-shell Lagrangian. This reveals the duality between Riemannian metric and teleparallel gravity, and a new candidate theory for three-dimensional massive gravity which we call teleparallel topologically massive gravity., 41+25 pages; v2: appendix D on Kosmann derivative and symplectic symmetries added, references added

The present study examines the possible effect of the novel hybrid molecule JM-20 (3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-411-dihydro-1H-pyrido[2,3-b] [1,5] benzodiazepine) on pain-related behaviours in a persistent pain model (5% formalin test) and in the neutrophil migration events during the inflammatory process. It further introduces JM-20 in a chronic constriction injury (CCI) model to clarify the possible subjacent mechanisms with its consequent clinical relevance. A single administration of JM-20 (20 or 40 mg/kg, per os [p.o.]) decreased licking/biting exclusively in the tonic phase of the formalin test in a GABA/benzodiazepine (BZD) receptor antagonist flumazenil-sensitive manner. JM-20 reduced in vivo neutrophil migration, rolling and adhesion to the endothelium induced by intraperitoneal administration of carrageenan in mice. In addition, plasma extravasation and tumour necrosis factor alpha production in the peritoneal fluid were decreased. Treatment with JM-20 (20 mg/kg, p.o.) for 7 days after CCI reduced mechanical hypersensitivity in a NG-monomethyl-l-arginine (L-NMMA)/methylene blue/glibenclamide-sensitive manner. Histopathological signs of Wallerian degeneration (WD) of the sciatic nerve were also attenuated, as well as interleukin-1 beta release in the spinal cord. The nitrate/nitrite concentration was increased centrally and did not show differences at the peripheral nerve level. The findings of this study suggest JM-20 can decrease persistent pain. A transient activity of its BDZ portion on nociceptive pathways mediated by GABA/BDZ receptors in association with its anti-inflammatory properties could be at least partially involved in this effect. JM-20 decreased CCI-induced mechanical hypersensitivity via the l-arginine/nitric oxide (NO)/cyclic GMP-sensitive ATP-sensitive potassium channel pathway. Its neuroprotective ability by preventing WD could be implicated in its anti-neuropathic mechanisms.

Based on the insight gained by many authors over the years on the structure of the Einstein–Hilbert, Gauss–Bonnet and Lovelock gravity Lagrangians, we show how to derive-in an elementary fashion-their first-order, generalized ‘Arnowitt–Deser–Misner’ Lagrangian and associated Hamiltonian. To do so, we start from the Lovelock Lagrangian supplemented with the Myers boundary term, which guarantees a Dirichlet variational principle with a surface term of the form π ij δh ij , where π ij is the canonical momentum conjugate to the boundary metric h ij . Then, the first-order Lagrangian density is obtained either by integration of π ij over the metric derivative ∂ w h ij normal to the boundary, or by rewriting the Myers term as a bulk term.

One important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported the significant antitumor effect induced by the immunization with our human papillomavirus therapeutic protein-based vaccine (LALF32-51-E7) without adjuvant and admixed with clinically relevant adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study, we evaluated the efficacy of the above mentioned vaccine formulations in controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic clone named TC-1* and other intravenous injection site less stressful than the tail vein. We generated a lung metastasis model by injecting TC-1* cells into the retro-orbital venous sinus and this is the first study describing it. Also, this is the first study that demonstrates the efficacy of the immunization with LALF32-51-E7 without adjuvant and admixed with VSSP or Al(OH)3 in controlling metastatic tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be used to test the efficacy of other immunotherapeutic strategies based on E6/E7 antigens.

We present a Born-Infeld gravity theory based on generalizations of Maxwell symmetries denoted as $\mathfrak{C}_{m}$. We analyze different configuration limits allowing to recover diverse Lovelock gravity actions in six dimensions. Further, the generalization to higher even dimensions is also considered., v3, 15 pages, two references added, published version

Objective: The aim of this study was to evaluate the antinociceptive activity of the methanol extract of Tabebuia hypoleuca stems (THME). Materials and Methods: The animals were divided into 5 groups of 8 mice for each test (negative controls, positive controls, and 3 groups treated with THME at doses of 150, 300, and 500 mg/kg, p.o.). The antinociceptive effect of THME was evaluated using the writhing, formalin, tail flick, and hot plate models in mice. Results: In the writhing test, THME (150, 300, and 500 mg/kg) produced significantly (p < 0.001) fewer writhes induced by acetic acid than in the control group. In the formalin test, the licking time for THME at doses of 300 and 500 mg/kg was significantly shorter (p < 0.001) compared to the control group in the first phase of the formalin test, whereas in the second phase only the dose of 500 mg/kg showed an antinociceptive effect. In addition, THME at doses of 300 and 500 mg/kg significantly increased the latency time in the tail flick test (p < 0.05 and p < 0.001, respectively) and in the hot plate test (p < 0.01 and p < 0.001, respectively) compared to the control group. Conclusions: These results show that THME had antinociceptive activity using several models of nociception, and they suggest that the effect is mediated by the participation of both peripheral and central antinociceptive mechanisms.

Objective: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages. Methods: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined. Results: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions. Conclusions: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory de?cits associated with AD in humans.

In this work we present a BMS-like ansatz for a Chern-Simons theory based on the semi-simple enlargement of the Poincaré symmetry, also known as AdS-Lorentz algebra. We start by showing that this ansatz is general enough to contain all the relevant stationary solutions of this theory and provides with suitable boundary conditions for the corresponding gauge connection. We find an explicit realization of the asymptotic symmetry at null infinity, which defines a semi-simple enlargement of the $$ \mathfrak{b}\mathfrak{m}{\mathfrak{s}}_3 $$ b m s 3 algebra and turns out to be isomorphic to three copies of the Virasoro algebra. The flat limit of the theory is discussed at the level of the action, field equations, solutions and asymptotic symmetry.

We introduce an alternative way of closing Maxwell like algebras. We show, through a suitable change of basis, that resulting algebras are given by the direct sums of the AdS and the Maxwell algebras already known in the literature. Casting the result into the $S$-expansion method framework ensures the straightaway construction of the gravity theories based on a found enlargement., Comment: v2, 12 pages, version accepted for publication in Physics Letters B

In this paper we show how to translate into tensorial language the Chern-Weil theorem for the Lorentz symmetry, which equates the difference of the Euler densities of two manifolds to the exterior derivative of a transgression form. For doing so we need to introduce an auxiliary, hybrid, manifold whose geometry we construct explicitely. This allows us to find the vector density, constructed out of spacetime quantities only, whose divergence is the exterior derivative of the transgression form. As a consequence we can show how the Einstein-Hilbert, Gauss-Bonnet and, in general, the Euler scalar densities can be written as the divergences of genuine vector densities in the critical dimensions $D=2,4$, etc. As Lovelock gravity is a dimensional continuation of Euler densities, these results are of relevance for Gauss-Bonnet and, in general, Lovelock gravity. Indeed, these vectors which can be called generalized Katz vectors ensure, in particular, a well-posed Dirichlet variational principle., 15 pages

We study a three-dimensional Chern-Simons gravity theory based on the Maxwell algebra. We find that the boundary dynamics is described by an enlargement and deformation of the $\mathfrak{bms}_3$ algebra with three independent central charges. This symmetry arises from a gravity action invariant under the local Maxwell group and is characterized by presence of Abelian generators which modify the commutation relations of the super-translations in the standard $\mathfrak{bms}_3$ algebra. Our analysis is based on the charge algebra of the theory in the BMS gauge, which includes the known solutions of standard asymptotically flat case. The field content of the theory is different than the one of General Relativity, but it includes all its geometries as particular solutions. In this line, we also study the stationary solutions of the theory in ADM form and we show that the vacuum energy and the vacuum angular momentum of the stationary configuration are influenced by the presence of the gravitational Maxwell field., Comment: v3, 23 pages, introduction extended, minor correction, references added, Published version

Chitosan is a natural polymer with excellent properties such as biocompatibility, biodegradability, non-toxicity and adsorptive abilities. We obtained chitosan derived from Panurilus argus lobster shell and its lactate and acetate salts to introduce in pharmaceutical industry. We examined the single and repeated dose toxicity of chitosan and its lactate and acetate salts. Single oral doses of 2000 mg/kg were well tolerated for all three materials. In the repeat dose tests, animals treated with chitosan only show a slight erythrocytes increase. Variations in erythrocyte and leukocyte count and some biochemical parameters were observed in animals treated with chitosan acid salts. One g/kg orally was found to be the subacute NOAEL for chitosan due to the hematological findings observed were not considered adverse. Chitosans obtained from Panurilus argus lobster shell have low toxicity and may be safe in rats because it did not cause any lethality or changes in the general behavior in both the single and repeated dose toxicity studies.

The S-expansion method is a generalization of the In\"{o}n\"{u}-Wigner (IW) contraction that allows to study new non-trivial relations between different Lie algebras. Basically, this method combines a Lie algebra $\mathcal{G}$ with a finite abelian semigroup $S$ in such a way that a new S-expanded algebra $\mathcal{G}_{S}$ can be defined. When the semigroup has a zero-element and/or a specific decomposition, which is said to be resonant with the subspace structure of the original algebra, then it is possible to extract smaller algebras from $\mathcal{G}_{S}$ which have interesting properties. Here we give a brief description of the S-expansion, its applications and the main motivations that lead us to elaborate a Java library, which automatizes this method and allows us to represent and to classify all possible S-expansions of a given Lie algebra., Comment: 7 pages, 1 figure, Talk at ACAT 2017, Seattle, USA, to appear in Proceedings of ACAT 2017

In this article we describe the Java library that we have recently constructed to automatize the S-expansion method, a powerful mathematical technique allowing to relate different Lie algebras. An important input in this procedure is the use of abelian semigroups and thus, we start with a brief review about the classification of non-isomorphic semigroups made in the literature during the last decades, and explain how the lists of non-isomorphic semigroups up to order 6 can be used as inputs in many of the methods of our library. After describing the main features of the classes that compose our library we present a new method called fillTemplate which tuns out to be very useful to answer whether two given algebras can be S-related., Comment: 6 pages, Talk at ACAT 2017, Seattle, USA, to appear in Proceedings of ACAT 2017

One important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported the significant antitumor effect induced by the immunization with our human papillomavirus therapeutic protein-based vaccine (LALF

We explore the possibility of finding Pure Lovelock gravity as a particular limit of a Chern-Simons action for a specific expansion of the AdS algebra in odd dimensions. We derive this relation at the level of the action in five and seven dimensions. Additionally we provide the general result for higher dimensions and discuss some issues arising from the obtained dynamics., 23 pages; V4: published version

We study dynamical structure of Pure Lovelock gravity in spacetime dimensions higher than four using the Hamiltonian formalism. The action consists of cosmological constant and a single higher-order polynomial in the Riemann tensor. Similarly to Einstein-Hilbert action, it possesses a unique constant curvature vacuum and charged black hole solutions. We analyze physical degrees of freedom and local symmetries in this theory. In contrast to the Einstein-Hilbert case, a number of degrees of freedom depends on the background and can vary from zero to the maximal value carried by the Lovelock theory., Comment: 23 pages, no figures

It is shown that the topological action for gravity in 2n-dimensions can be obtained from the ( 2 n + 1 ) -dimensional Chern–Simons gravity genuinely invariant under the Poincare group. The 2n-dimensional topological gravity is described by the dynamics of the boundary of a ( 2 n + 1 ) -dimensional Chern–Simons gravity theory with suitable boundary conditions. The field ϕ a , which is necessary to construct this type of topological gravity in even dimensions, is identified with the coset field associated with the non-linear realizations of the Poincare group ISO ( d − 1 , 1 ) .

The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30.

Increased formation of MG (methylglyoxal) and related protein glycation in diabetes has been linked to the development of diabetic vascular complications. Diabetes is also associated with impaired wound healing. In the present study, we investigated if prolonged exposure of rats to MG (50–75 mg/kg of body weight) induced impairment of wound healing and diabetes-like vascular damage. MG treatment arrested growth, increased serum creatinine, induced hypercholesterolaemia (all P

The liver is damaged by sustained ischaemia during liver transplantation, and the reperfusion after ischaemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischaemia/reperfusion (I/R) injury through different mechanisms. The aim of this study was to investigate the influence of the inhibition of protein synthesis on the protective actions conferred by OzoneOP in hepatic I/R. Rats were treated with cycloheximide (CHX) in order to promote protein synthesis inhibition after OzoneOP treatment. Plasma transaminases, malondialdehyde and 4-hydroxyalkenals and morphological characteristics were measured as an index of hepatocellular damage; Cu/Zn-superoxide dismutase (SOD), Mn-SOD, catalase, total hydroperoxides and glutathione levels as markers of endogenous antioxidant system. OzoneOP increased Mn-SOD isoform and ameliorated mitochondrial damage. CHX abrogated the protection conferred by OzonoOP and decreased Mn-SOD activity. Cellular redox balance disappeared when CHX was introduced. Protein synthesis is involved in the protective mechanisms mediated by OzoneOP. Ozone treatment preserved mitochondrial functions and cellular redox balance.

Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys of animals and humans and it has been well documented that reactive oxygen species and the renal antioxidant system are strongly involved in acute renal damage induced by CDDP. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in chronic renal damage induced by repeated doses of CDDP (1 mg/kg intraperitoneally twice weekly during 10 weeks in rats). In order to elucidate it, serum creatinine and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal superoxide dismutase and glutathione peroxidase activities were measured in the kidney homogenates of chronically CDDP-treated rats and additionally histological studies were performed in the rat kidneys. The chronic treatment with CDDP induced a significant increase in creatinine and urea levels in serum, but the other parameters mentioned above were not significantly modified as compared to the values in nontreated rats. Taking into account these results, we conclude that chronic CDDP administration induces also severe nephrotoxicity, in contrast to CDDP acute application, without any significant modification in the activity of relevant antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by which the role of the antioxidant system in chronic nephrotoxicity induced by CDDP in rats is uncertain.

The h-R3 is a humanized monoclonal antibody (Mab) that binds to the external domain of the human epidermal growth factor receptor (EGF-R). It has being used for the treatment of head and neck tumors. Since it is known that different animal species have different EGF-R amino acid sequences, it raises the handicap that, a priori, the animal species relevant for the pharmacodynamic, pharmacokinetic, and toxicologic studies of this Mab are unknown. To elucidate relevant laboratory animal species, the authors investigated the immunohistochemical recognition by h-R3 Mab of EGF-R in small skin biopsy samples obtained from NMRI nu/nu, C57Bl/6, and OF-1 mice; Sprague-Dawley rats; Hartley guinea pigs; New Zealand rabbits; and Cercopithecus aethiops and Macaca fascicularis monkeys. Additionally, three human skin biopsies were obtained from trauma victims. The immunolocalization of EGF-R in different tissue sections was performed using the avidin-biotin peroxidase complex (ABC) technique. The skin sections from different tissues were tested with the biotinylated h-R3 Mab or with a biotinylated irrelevant Mab, used as negative control. The staining intensity was qualified as:-, no staining; +, weak staining; ++, moderate staining; +++, strong staining. Macaca fascicularis monkey, New Zealand rabbit, and OF-1 mouse skins had a strong staining intensity; Cercopithecus aethiops monkey and Sprague-Dawley rat skins showed a moderate to strong staining intensity; C57Bl/6 mouse skins showed a moderate staining intensity. No staining was observed in the skins from Hartley guinea pigs and MNRI nu/nu mice. The fact that h-R3 Mab recognizes other animal EGF receptors in addition to the human EGF-R makes it possible to perform relevant pharmacodynamic, pharmacokinetic, and toxicologic studies in some laboratory animals.

El Factor de Transferencia es un agente natural que aumenta la capacidad para combatir las enfermedades y mejorar la calidad de vida, ha sido usado éxitosamente para tratar enfermedades virales, parasitarias, neurológicas, micóticas y autoinmunes y también utilizado en pacientes que no responden a prescripciones convencionales o que desarrollan reacciones de toxicidad severas a estas. Este producto obtenido a partir de células sin inducir (por el virus Sendai) constituye una nueva y muy apropiada formulación teniendo en cuenta el método de obtención. La dosis terapéutica en humanos es de 1 mg/mL y su frecuencia de administración está asociada a la patología del paciente. Por su gran importancia para su uso en humanos, se realizó un ensayo toxicológico (toxicología aguda), para determinar la seguridad del producto. Se utilizaron tres dosis superiores a la terapéutica. Se realizaron observaciones clínicas diarias y determinaciones del peso corporal de forma semanal. Transcurrida la fase experimental (14 d), se realizó el sacrificio de los animales, todo lo cual se llevó a cabo cumpliendo las normas éticas, con análisis macroscópicos y microscópicos de órganos relacionados con el sistema hemolinfopoyético y el hígado. Al comparar los resultados de los grupos tratados con el placebo, no se observaron diferencias significativas en el peso corporal ni se reportaron efectos adversos en los órganos estudiados, lo que permitió concluir que la nueva formulación no resulta tóxica.

Se estudió la respuesta del tejido óseo a implantes de carbonato de calcio aragonito (CCA). Se utilizaron implantes de Hidroxiapatita Coralina (HA) en la misma forma y proceder quirúrgico como biomaterial de control comparativo. Se investigó el efecto de la composición química sobre la capacidad de curación y la velocidad de reabsorción de ambos biomateriales implantados en el fémur de ratas. Los animales fueron sacrificados a los 3, 7, 15, 21 y 60 d y los implantes fueron recuperados para los análisis posteriores. La evaluación se realiz ó mediante técnicas de microscopia óptica, estudios histológicos y radiográficos, análisis químico cuantitativo de calcio y fósforo y espectroscopia IR de Transformada de Fourier (FT-IR). Se encontró que ambos biomateriales fueron bien asimilados y se integraron al tejido óseo circundante. En el caso de la Hidroxiapatita se observó que a los 60 d el defecto óseo fue reparado, pero el biomaterial mantuvo la misma apariencia inicial. Por el contrario, en ese mismo período, el implante de coral (CCA) disminuyó su tamaño y su apariencia resultó más parecida a la del tejido circundante. Los estudios histológicos mostraron la misma capacidad osteogénica en ambos biomateriales en los primeros 7 d de implantados, pero a los 15 d se aprecia una mayor velocidad de sustitución del tejido fibrovascular por hueso en el caso del CCA. La cinética de biodegradación calculada a partir de los análisis químicos (relación Ca/P) y de los espectros IR coincide con las observaciones histológicas y muestra una mayor velocidad de reabsorción de los implantes de carbonato de calcio (CCA). Se encontró que la transformación del CCA produce una fase similar a la del hueso debido a la pérdida paulatina del anión carbonato y la incorporación del fosfato correspondiente. El CCA también presentó una mayor capacidad osteogénica en comparación con la HA. A los 60 d el (42,5 ± 3,2) % del CCA originalmente implantado se transformó en fosfato de calcio y la velocidad de este proceso se incrementó de (0,22 ± 0,08) %/d a los 7 d hasta (0,7 ± 0,1) %/d a los 60 d de implantado. Los implantes de HA no experimentaron cambios en el período analizado (60 d). En conclusión, igual que la hidroxiapatita porosa, el biomaterial de aragonito estimula la proliferación de tejido vivo hacia el interior de los poros, pero con una mayor velocidad de reabsorción y de generación de nuevo hueso. Estos resultados sugieren que la velocidad de reabsorción de este tipo de biomaterial de implante puede ser controlada en dependencia de la relación fosfato/carbonato en su composición química inicial.

A biochemical and morphofunctional renal study, applying different sessions of rectal ozone (O3) before a warm ischemia, was performed. Rats were divided in: 1-control, a medial abdominal incision was performed for the exposure of the kidneys; 2-ischemia, animals with a bilateral renal ischemia (30 min), with subsequent reperfusion (3 h); groups 3, 4 and 5 – (O3+ischemia), as group 2, but with previously treatment of 5, 10 and 15 sessions of rectal ozone, respectively; groups 6, 7 and 8 – (O2+ischemia), as groups 3, 4 and 5, respectively, but using rectal oxygen. A significant decrease of the flow and renal filtration, with high values of fructosamine and phospholipase A2, in the ischemia and oxygen groups, with respect to control and ozone groups was obtained without any statistical difference among them. Morphological alterations were significantly less in the groups pretreated with ozone, with better results for 10 and 15 sessions.