Electronic signatures of successive itinerant, antiferromagnetic transitions in hexagonal La2Ni7.

We use high-resolution angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT) calculations to study the electronic and magnetic properties of La2Ni7, an itinerant magnetic system with a series of three magnetic transition temperatures upon cooling, which end in a weak antiferromagnetic ground state. Our APRES data reveal several electron and hole pockets that have hexagonal symmetry near the Γ point. We observe significant reconstruction of the band structure upon successive magnetic transitions atT1∼ 61 K,T2∼ 57 K andT3∼ 42 K. Several features observed in ARPES data were reasonably well reproduced by DFT calculations, while others were not. In particular, the flat band nearEFpredicted by DFT in antiferromagnet (AFM) state, was seemingly absent in ARPES data. Our results detail the effects of magnetic ordering on the electronic structure in a Ni-based weak AFM and highlight challenges of current computational methods.

Influence of Tooth Pigmentation on H2O2 Diffusion and Its Cytotoxicity After In-office Tooth Bleaching.

CLINICAL RELEVANCE: Pigments in tooth structures affect the diffusion of H2O2 through enamel and dentin. The bleaching methodology can be impacted. SUMMARY: Objective: The aim of this study was to evaluate the influence of the presence of pigments in tooth structures on the trans-enamel and trans-dentin diffusion of hydrogen peroxide (H2O2) and its cytotoxicity after carrying out an in-office bleaching therapy.Methods and Materials: A bleaching gel with 35% H2O2 was applied for 45 minutes (three times for 15 minutes) on enamel and dentin discs (n=6), either previously submitted to the intrinsic pigmentation protocol with a concentrated solution of black tea, or not, defining the following groups: G1, unbleached untreated discs (control 1); G2, unbleached pigmented discs (control 2); G3, bleached untreated discs; G4, bleached pigmented discs. The discs were adapted to artificial pulp chambers, which were placed in wells of 24-well plates containing 1 mL culture medium (Dulbecco's modified Eagle's medium [DMEM]). After applying the bleaching gel on enamel, the extracts (DMEM + components of bleaching gel that diffused through the discs) were collected and then applied on the cultured MDPC-23 odontoblast-like cells. Cell viability (methyl tetrazolium assay and Live & Dead, Calcein AM, and ethidium homodimer-1 [EthD-1] probes), the amount of H2O2 that diffused through enamel and dentin (leuco-crystal violet product), and the H2O2-mediated oxidative cell stress (SOx) and components of degradation were assessed (analysis of variance/Tukey; α=0.05).Results: There was no significant difference between the groups G1 and G2 for all the parameters tested (p>0.05). Reduction in the trans-enamel and trans-dentin diffusion of H2O2 occurred for G4 in comparison with G3. Significantly lower cell viability associated with greater oxidative stress was observed for G3 (p<0.05). Therefore, in-office tooth bleaching therapy performed in pigmented samples caused lower cytotoxic effects compared with untreated samples submitted to the same esthetic procedure (p<0.05).Conclusion: According to the methodology used in this investigation, the authors concluded that the presence of pigments in hard tooth structures decreases the trans-enamel and trans-dentin diffusion of H2O2 and the toxicity to pulp cells of an in-office bleaching gel with 35% H2O2.

Fractional topological phase measurement with a hyperentangled photon source.

Pairs of photons simultaneously entangled in their path and polarization degrees of freedom are used to measure the topological phase acquired by bipartite entangled states. Conditional phase local unitary operations having the polarization degree of freedom as the control variable are applied. Qudits of arbitrary dimensions are encoded on the photons transverse positions while polarization entanglement is used as an auxiliary resource for quantum interference measurements. With this scheme the fractional phases predicted for dimensions d = 2, 3 and 4 could be measured with visibilities for the interference curves beyond the limit allowed for classical sources, which is expected for a source of quantum correlated photons. The strategy of perform a quantum interferometry experiment with photons entangled in an auxiliary degree of freedom and apply unitary local operations conditioned to this auxiliary variable shows an increase to the signal to noise ratio, simplifies alignment and can be used in different applications. This offers an interesting perspective for the efficient implementation of phase gates in quantum computing with hyperentangled photon sources in polarization and path degrees of freedom. Furthermore, one can conjecture whether the measured phase can serve as a dimensionality identifier of the Hilbert space dimension for an unknown state preparation.

A DFT investigation of the role of oxygen vacancies on the structural, electronic and magnetic properties of ATiO3 (A = Mn, Fe, Ni) multiferroic materials.

In order to achieve deep insight into the multiferroic behavior and electronic properties of intrinsic oxygen vacancies in ATiO3 (A = Mn, Fe, Ni), first-principles calculations based on hybrid density functional theory were carried out for bulk and non-polar (110) surface models. We found that the formation of an oxygen vacancy is accompanied by structural and electronic disorders in the constituent clusters of [TiO6] and [AO6] in ATiO3, that become [TiO5] and [AO5], respectively. This perturbation contributes to the generation of intermediary energy levels in the band gap region, thus narrowing the required excitation energy. In addition, the remaining electrons are mainly trapped in the empty 3d orbitals of the Ti cations neighboring the oxygen vacancy, generating [TiO5]' (3d1) that mediates an antiferromagnetic to ferromagnetic transition in MnTiO3 and FeTiO3 materials. In particular, MnTiO3 surfaces show exposed [TiO4]' species that are responsible for its half-metallic behavior. The present work provides compelling evidence that controlling oxygen vacancies can be a valuable strategy to tailor the multiferroic properties of ATiO3 materials.

Curva de crescimento em altura na cernelha de equinos da raça Mangalarga Marchador considerando-se heterocedasticidade / Growth curve for height at withers of Mangalarga Marchador horses with heterocedasticity

Objetivou-se, com este estudo, avaliar o ajuste dos modelos de Brody, Gompertz, Logístico e Von Bertalanffy aos dados de altura na cernelha de equinos Mangalarga Marchador, ponderando pelo inverso da variância, a fim de selecionar o melhor modelo e predizer sobre o crescimento e a maturidade dos animais dessa raça. Foram utilizados dados de 230 equinos dos seis aos 176 meses de idade, os quais foram divididos por sexo e em 16 classes de idade. Os modelos estudados foram comparados segundo os avaliadores de qualidade: coeficiente de determinação (R2); desvio padrão residual (DPR) e critério de informação de Akaike (AIC). A estimação dos parâmetros dos modelos foi realizada pelo método de mínimos quadrados ponderado no software R. Todos os modelos avaliados se mostraram adequados para descrever a curva de crescimento em ambos os sexos. Perante os avaliadores utilizados, o modelo Logístico foi o mais adequado para descrever as curvas de crescimento em altura na cernelha nos dois sexos da raça Mangalarga Marchador. Observou-se também um crescimento acelerado nos primeiros meses de idade. Os animais machos atingiram uma altura adulta maior, porém as fêmeas são mais precoces, pois apresentaram maior estimativa para o índice de maturidade.(AU)

This work aimed to evaluate the fit of models Brody, Gompertz, Logistic and Von Bertalanffy to height at the withers of Mangalarga Marchador horses, weighed by the inverse of variance, in order to select the best model and predict growth and maturity of this breed pf animals. We used data of 230 equines from 06 to 176 months of age who were divided by sex and 16 age classes. The models were compared according to the quality assessors: coefficient of determination (R2); residual standard deviation (RSD) and Akaike information criteria (AIC). The estimation of the parameters from models was performed by the weighted least squares method in Software R. All models evaluated were suitable to describe the growth curve in both sexes. In view of the evaluators used, the logistic model was the most suitable to describe the growth curves in withers height in both sexes for the race Mangalarga Marchador. A strong growth at first age was also observed. The males reached a greater adult height, but females did so sooner, because they presented higher estimates for the maturity index.(AU)

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats.

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in ß-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, ß-cell hypersecretion, a higher percentage of islets and ß-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

Tuning the electronic hybridization in the heavy fermion cage compound YbFe2Zn20 with Cd doping.

The tuning of the electronic properties of heavy fermion compounds by chemical substitution provides excellent opportunities for further understanding the physics of hybridized ions in crystal lattices. Here we present an investigation on the effects of Cd doping in flux-grown single crystals of the complex intermetallic cage compound YbFe2Zn20, which has been described as a heavy fermion with a Sommerfeld coefficient of 535 mJ mol(-1) · K(-2). The substitution of Cd for Zn disturbs the system by expanding the unit cell and, in this case, the size of the Zn cages that surround the Yb and Fe. With an increasing amount of Cd, the hybridization between the Yb 4f electrons and the conduction electrons is weakened, as shown by a decrease in the Sommerfeld coefficient, which should be accompanied by a valence shift of the Yb(3+) due to the negative chemical pressure effect. This scenario is also supported by the low temperature DC magnetic susceptibility, which is gradually suppressed and shows an increment of the Kondo temperature, based on a shift to higher temperatures of the characteristic broad susceptibility peak. Furthermore, the DC resistivity decreases with the isoelectronic substitution of Cd for Zn, contrary to expectations in an increasingly disordered system, and implying that the valence shift is not related to charge carrier doping. The combined results demonstrate the excellent complementarity between positive physical pressure and negative chemical pressure, and point to a rich playground for exploring the physics and chemistry of strongly correlated electron systems in the general family of Zn20 compounds, despite their structural complexity.

Conduction electron spin resonance in the α-Yb1-xFexAlB4 (0 ⩽ x ⩽ 0.50) and α-LuAlB4 compounds.

ß-YbAlB4 has become one of the most studied heavy fermion systems since its discovery due to its remarkable physical properties. This system is the first reported Yb-based heavy-fermion superconductor (HFS) for which the low-T superconducting state emerges from a non-fermi-liquid (NFL) normal state associated with quantum criticality Nakatsuji et al 2008 Nature 4 603. Additionally, it presents a striking and unprecedented electron spin resonance (ESR) signal which behaves as a conduction electron spin resonance (CESR) at high temperatures and acquires features of the Yb(3+) local moment ESR at low temperatures. The latter, also named Kondo quasiparticles spin resonance (KQSR), has been defined as a 4f-ce strongly coupled ESR mode that behaves as a local probe of the Kondo quasiparticles in a quantum critical regime, Holanda et al 2011 Phys. Rev. Lett. 107 026402. Interestingly, ß-YbAlB4 possesses a previously known structural variant, namely the α-YbAlB4, phase which is a paramagnetic Fermi liquid (FL) at low temperatures Macaluso et al 2007 Chem. Mater. 19 1918. However, it has been recently suggested that the α-YbAlB4 phase may be tuned to NFL behavior and/or magnetic ordering as the compound is doped with Fe. Here we report ESR studies on the α-Yb1-xFexAlB4 (0 â©½ x â©½ 0.50) series as well as on the reference compound α-LuAlB4. For all measured samples, the observed ESR signal behaves as a CESR in the entire temperature range (10 K â‰² T â‰² 300 K) in clear contrast with what has been observed for ß-YbAlB4. This striking result indicates that the proximity to a quantum critical point is crucial to the occurrence of a KQSR signal.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice.

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/- -challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Ability of immunodiagnostic tests to differentiate between dogs naturally infected with Leishmania infantum and Leishmune(®)-vaccinated dogs.

Visceral leishmaniasis (VL) is a serious chronic disease with a lethality rate of up to 10% in humans. In urban areas of Brazil, dogs are the main reservoirs of the etiological agent (Leishmania infantum) of VL, and the Brazilian Ministry of Health recommends the euthanasia of animals that are seropositive in both the immunochromatographic dual path platform rapid test (DPP(®); Bio-Manguinhos) and the enzyme-linked immunosorbent assay (ELISA) with an L. major-like antigen (Bio-Manguinhos). Vaccination is an additional tool in the control of canine VL, but the use of Leishmune(®) (Zoetis Indústria de Produtos Veterinários, São Paulo, SP, Brazil), which contains the fucose mannose ligand (FML) isolated from L. donovani, is not currently recommended by the Brazilian Ministry of Health because vaccinated animals may exhibit positive serology and there are reservations regarding the efficacy of the vaccine. The aims of the present study were: (i) to verify the abilities of the fast agglutination screening test (FAST), the direct agglutination test (DAT), the indirect fluorescent-antibody test (IFAT), the DPP rapid test, and ELISA tests with L. major-like and FML antigens to differentiate between L. infantum-infected and Leishmune(®)-vaccinated dogs, and (ii) to analyze the sensitivities and specificities of the different methods. The reactivities to these tests of Leishmune(®)-vaccinated dogs (n = 71), asymptomatic (n = 20) and symptomatic (n = 20) naturally infected dogs, and unvaccinated healthy control dogs (n = 5) were compared. None of the Leishmune(®)-vaccinated dogs tested seropositive in FAST and DAT, although one dog was reactive to DPP and four dogs to ELISA/L. major-like and IFAT tests. While 69 (97%) of vaccinated dogs reacted to ELISA/FML, only one was seropositive in both ELISA/L. major-like and IFAT tests. Individually, all immunodiagnostic tests presented high specificities and positive likelihood ratios (LR+), and high specificity values were obtained when the tests were considered in pairs. However, sensitivity and LR- values were low for ELISA/L. major-like and IFAT tests individually, and for all pair combinations of tests except for FAST with DPP.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats.

The parasympathetic nervous system is important for ß-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic ß-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca(2+) mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and ß-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and ß-cell area/pancreas section, respectively. Also, the ß-cell number per ß-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca(2+) mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater ß-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

Bothrops jararacussu snake venom-induces a local inflammatory response in a prostanoid- and neutrophil-dependent manner.

Local tissue reactions provoked by Bothrops venoms are characterized by edema, hemorrhage, pain, and inflammation; however, the mechanisms of tissue damage vary depending upon the species of snake. Here, we investigated the mechanisms involved in the local inflammatory response induced by the Bothrops jararacussu venom (BjcuV). Female Swiss mice were injected with either saline, BjcuV (0.125-8 µg/paw) or loratadine (an H1 receptor antagonist), compound 48/80 (for mast cell depletion), capsaicin (for C-fiber desensitization), infliximab (an anti-TNF-α antibody), indomethacin (a non-specific COX inhibitor), celecoxib (a selective COX-2 inhibitor) or fucoidan (a P- and L-selectins modulator) given before BjcuV injection. Paw edema was measured by plethysmography. In addition, paw tissues were collected for the measurement of myeloperoxidase activity, TNF-α and IL-1 levels, and COX-2 immunoexpression. The direct chemotactic effect of BjcuV and the in vitro calcium dynamic in neutrophils were also investigated. BjcuV caused an edematogenic response with increased local production of TNF-α and IL-1ß as well as COX-2 expression. Both edema and neutrophil migration were prevented by pretreatment with indomethacin, celecoxib or fucoidan. Furthermore, BjcuV induced a direct in vitro neutrophil chemotaxis by increasing intracellular calcium. Therefore, BjcuV induces an early onset edema dependent upon prostanoid production and neutrophil migration.

Gd3+ spin-lattice relaxation via multi-band conduction electrons in Y(1-x)Gd(x)In3: an electron spin resonance study.

Interest in the electronic structure of the intermetallic compound YIn3 has been renewed with the recent discovery of superconductivity at T ∼ 1 K, which may be filamentary in nature. In this work we perform electron spin resonance (ESR) experiments on Gd(3+) doped YIn3 (Y1-xGdxIn3; 0.001 ⪅ x ⩽̸ 0.08), showing that the spin-lattice relaxation of the Gd(3+) ions, due to the exchange interaction between the Gd(3+) localized magnetic moment and the conduction electrons (ce), is processed via the presence of s-, p- and d-type ce at the YIn3 Fermi level. These findings are revealed by the Gd(3+) concentration dependence of the Korringa-like relaxation rate d(ΔH)/dT and g-shift (Δg = g - 1.993), that display bottleneck relaxation behavior for the s-electrons and unbottleneck behavior for the p- and d-electrons. The Korringa-like relaxation rates vary from 22(2) Oe/K for x ⪅ 0.001 to 8(2) Oe/K for x = 0.08 and the g-shift values change, respectively, from a positive Δg = +0.047(10) to a negative Δg = -0.008(4). Analysis in terms of a three-band ce model allows the extraction of the corresponding exchange interaction parameters Jfs, Jfp and Jfd.

Physical exercise introduced after weaning enhances pancreatic islet responsiveness to glucose and potentiating agents in adult MSG-obese rats.

Physical exercise represents an alternative way to prevent and/or ameliorate chronic metabolic diseases. Disruption of sympathetic nervous system (SNS) activity contributes to adiposity in obese subjects. Here, we verified the preventive effect of swimming training upon adiposity, adrenal catecholamine storage, and pancreatic islet function in obese monosodium glutamate (MSG)-treated rats. Male neonatal Wistar rats received MSG (4 mg/g body weight) during the first 5 days of life and, at weaning, half of the rats were submitted to swimming training, 30 min/day, 3 days a week, until 90 days of age (exercised rats: MSGex). Half of the rats were used as controls (sedentary group, MSGsd). Exercise training (ET) decreased insulinemia and fat deposition in MSGex, and increased adrenal catecholamine content, compared with MSGsd rats. Insulinemia during the ivGTT was lower in MSGex rats, despite a lack of difference in glycemia. Swimming training enhanced insulin release in islets challenged by 2.8-8.3 mmol/l glucose, whereas, at supraphysiological glucose concentrations (11.1-16.7 mmol/l), MSGex islets secreted less insulin than MSGsd. No differences in insulin secretion were observed following l-arginine (Arg) or K(+) stimuli. In contrast, islets from MSGex rats secreted more insulin when exposed to carbachol (100 µmol/l), forskolin (10 µmol/l), or IBMX (1 mmol/l) at 8.3 mmol/l glucose. Additionally, MSGex islets presented a better epinephrine inhibition upon insulin release. These results demonstrate that ET prevented the onset of obesity in MSG rats, probably by enhancing adrenal catecholamine levels. ET ameliorates islet responsiveness to several compounds, as well as insulin peripheral action.

IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice.

Intestinal damage and severe diarrhea are serious side effects of cancer chemotherapy and constrain the usage of most such therapies. Here we show that interleukin-33 (IL-33) mediates the severe intestinal mucositis in mice treated with irinotecan (CPT-11), a commonly used cancer chemotherapeutic agent. Systemic CPT-11 administration led to severe mucosal damage, diarrhea, and body weight loss concomitant with the induction of IL-33 in the small intestine (SI). This mucositis was markedly reduced in mice deficient in the IL-33R (ST2(-/-)). Moreover, recombinant IL-33 exacerbated the CPT-11-induced mucositis, whereas IL-33 blockade with anti-IL-33 antibody or soluble ST2 markedly attenuated the disease. CPT-11 treatment increased neutrophil accumulation in the SI and adhesion to mesenteric veins. Supernatants from SI explants treated with CPT-11 enhanced transmigration of neutrophils in vitro in an IL-33-, CXCL1/2-, and CXCR2-dependent manner. Importantly, IL-33 blockade reduced mucositis and enabled prolonged CPT-11 treatment of ectopic CT26 colon carcinoma, leading to a beneficial outcome of the chemotherapy. These results suggest that inhibition of the IL-33/ST2 pathway may represent a novel approach to limit mucositis and thus improve the effectiveness of chemotherapy.

Targeted inhibition of IL-18 attenuates irinotecan-induced intestinal mucositis in mice.

BACKGROUND AND PURPOSE: Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the role of IL-18 in the pathogenesis of irinotecan-induced intestinal mucositis. EXPERIMENTAL APPROACH: Wild type (WT), IL-18 or caspase-1 knockout mice were treated with either saline or irinotecan (60 mg·kg⁻¹ per 4 days, i.p.) or the IL-18 binding protein (IL-18bp, 10 mg·kg⁻¹) before irinotecan. On day 5, diarrhoea was monitored and proximal intestinal strips were obtained for histopathology, in vitro gut contractility, myeloperoxidase (MPO) and inducible NOS (iNOS) activity, and detection of IL-18 expression. KEY RESULTS: Irinotecan induced severe diarrhoea accompanied by intestinal injury (villi shortening and increased crypt depth). Additionally, irinotecan treatment increased MPO and iNOS activity, iNOS immunostaining and IL-18 expression in WT mice compared with saline treatment. The IL-18 production was associated with macrophages. In vitro, intestinal smooth muscle strips were hyperresponsive to ACh after irinotecan treatment. Increases in MPO and iNOS activity, intestinal contractility and diarrhoea were prevented in caspase-1 knockout and IL-18 knockout mice, and in IL-18bp-treated WT mice. Furthermore, the Survival of irinotecan-treated mice was increased and iNOS immunoexpression and IL-18 production prevented in IL-18 knockout mice. CONCLUSIONS AND IMPLICATIONS: Targeting IL-18 function may be a promising therapeutic approach to decreasing the severity of intestinal mucositis during irinotecan treatment regimens.

Low-dose combination of alendronate and atorvastatin reduces ligature-induced alveolar bone loss in rats.

BACKGROUND AND OBJECTIVE: Atorvastatin (ATV) has bone anabolic properties, and alendronate (ALD) is an important antiresorptive drug. This study aimed to evaluate the effects of the combination of ALD and ATV on ligature-induced alveolar bone loss in rats. MATERIAL AND METHODS: Periodontitis was induced by ligature in 78 Wistar rats. Groups of six rats prophylactically received 0.9% saline (SAL), ALD (0.01 or 0.25 mg/kg subcutaneously) or ATV (0.3 or 27 mg/kg by gavage). Then, groups of six rats received the combination of ALD+ATV (0.25 mg/kg + 27 mg/kg, 0.01 mg/kg + 0.3 mg/kg, 0.25 mg/kg + 0.3 mg/kg or 0.01 mg/kg + 27 mg/kg) prophylactically. An extra group of six rats received therapeutic SAL or a lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) therapeutically. Three extra groups of six rats each received SAL or a lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) prophylactically or therapeutically for histometric and immunohistochemical analyses. The rats were killed on day 11 after ligature placement, and the maxillae were removed and processed for macroscopic, histomorphometric and TRAP immunohistochemical analyses. Gingival samples were collected to evaluate myeloperoxidase (MPO) activity. Blood samples were collected to measure serum bone-specific alkaline phosphatase (BALP) and transaminase levels and for hematological studies. Rats were weighed daily. RESULTS: All combined therapies prevented alveolar bone loss when compared with SAL or low doses of monotherapy (ALD or ATV) (p < 0.05). The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively), administered either prophylactically (39.0%) or therapeutically (53.5%), prevented alveolar bone loss. Decreases in bone and cementum resorption, in leukocyte infiltration and in immunostaining for TRAP and MPO activity corroborated the morphometric findings. The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) prevented BALP reduction (p < 0.05) and did not alter the level of serum transaminases. Moreover, the lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) also reduced neutrophilia and lymphomonocytosis and did not cause weight loss when compared with administration of SAL. CONCLUSION: The lower-dose combination of ALD+ATV (0.01 mg/kg + 0.3 mg/kg, respectively) demonstrated a protective effect on alveolar bone loss.