Opioid-induced hyperalgesia after rapid titration with intravenous morphine: Switching and re-titration to intravenous methadone

Rapid titration with intravenous morphine (IV-MO) provides fast and efficient pain relief in cancer patients with severe-excruciating pain. However, some patients, after an initially favourable response, can develop an hyperexcitated state unrelieved or worsened by further dose increments

Engineering Polymeric Nanosystems against Oral Diseases

Nanotechnology and nanoparticles (NPs) are at the forefront of modern research, particularly in the case of healthcare therapeutic applications. Polymeric NPs, specifically, hold high promise for these purposes, including towards oral diseases. Careful optimisation of the production of polymeric NPs, however, is required to generate a product which can be easily translated from a laboratory environment to the actual clinical usage. Indeed, considerations such as biocompatibility, biodistribution, and biodegradability are paramount. Moreover, a pre-clinical assessment in adequate in vitro, ex vivo or in vivo model is also required. Last but not least, considerations for the scale-up are also important, together with an appropriate clinical testing pathway. This review aims to eviscerate the above topics, sourcing at examples from the recent literature to put in context the current most burdening oral diseases and the most promising polymeric NPs which would be suitable against them

Engineering polymeric nanosystems against oral diseases

Nanotechnology and nanoparticles (NPs) are at the forefront of modern research, par-ticularly in the case of healthcare therapeutic applications. Polymeric NPs, specifically, hold high promise for these purposes, including towards oral diseases. Careful optimisation of the production of polymeric NPs, however, is required to generate a product which can be easily translated from a laboratory environment to the actual clinical usage. Indeed, considerations such as biocompati-bility, biodistribution, and biodegradability are paramount. Moreover, a pre-clinical assessment in adequate in vitro, ex vivo or in vivo model is also required. Last but not least, considerations for the scale-up are also important, together with an appropriate clinical testing pathway. This review aims to eviscerate the above topics, sourcing at examples from the recent literature to put in context the current most burdening oral diseases and the most promising polymeric NPs which would be suitable against them

Emissão de metano entérico e consumo alimentar residual em bovinos Nelore.

O objetivo do trabalho foi avaliar a emissão diária de metano entérico em bovinos Nelore com um ano de idade, previamente avaliados para o consumo alimentar residual (CAR). Foram avaliados 118 animais, machos e fêmeas, nascidos em 2010, provenientes do Centro APTA Bovinos de Corte-IZ/SP. O CAR foi estimado como o resíduo da equação de regressão do consumo de matéria seca (CMS) sobre o peso metabólico e o ganho médio diário (GMD) em teste pós-desmama de 110 dias de duração. Os animais foram classificados por CAR em três grupos: alto CAR (n= 36), médio CAR (n= 42) e baixo CAR (n= 40), levando-se em conta o desvio-padrão da média do CAR de cada sexo. Uma amostra representativa de 46 animais das classes alto e baixo CAR foi usada para avaliar a emissão diária de metano (CH4) por meio da metodologia do gás traçador hexafluoreto de enxofre com 7 dias consecutivos de coleta. Durante a coleta de metano o CMS foi também obtido. Apesar da diferença do CMS dos animais das duas classes de CAR, não houve diferença significativa na CH4. Quando a CH4 foi expressa em relação ao GMD, houve diferença significativa entre os animais mais e menos eficientes. Os animais mais eficientes (baixo CAR) emitem menos CH4 por kg de ganho de peso que os animais menos eficientes (alto CAR)

New Cases of Universality Theorem for Gravitational Theories

The "Universality Theorem" for gravity shows that f(R) theories (in their metric-affine formulation) in vacuum are dynamically equivalent to vacuum Einstein equations with suitable cosmological constants. This holds true for a generic (i.e. except sporadic degenerate cases) analytic function f(R) and standard gravity without cosmological constant is reproduced if f is the identity function (i.e. f(R)=R). The theorem is here extended introducing in dimension 4 a 1-parameter family of invariants R' inspired by the Barbero-Immirzi formulation of GR (which in the Euclidean sector includes also selfdual formulation). It will be proven that f(R') theories so defined are dynamically equivalent to the corresponding metric-affine f(R) theory. In particular for the function f(R)=R the standard equivalence between GR and Holst Lagrangian is obtained.Comment: 10 pages, few typos correcte

Determination of Tebuconazole and Penconazole Fungicides in Rat and Human Hair by Liquid Chromatography/Tandem Mass Spectrometry

RATIONALE: Tebuconazole (TEB) and penconazole (PEN) are widely applied fungicides and environmental contaminants; their toxicological properties include possible effects to the unborn child, therefore the evaluation of human exposure is relevant to risk assessment. Hair is a non-invasive specimen that incorporates pollutants allowing an extended exposure window to be surveyed. Aim of this work was to develop and validate an assay for the determination of TEB and PEN in human hair. METHODS: Under optimised conditions, analytes were extracted soaking hair in acetonitrile, in the presence of deuterated analogues, under heating and agitation. Chemical separation was achieved using a C18 reversed-phase chromatographic column and detection and quantification were performed, after a positive electrospray ionization, by triple quadrupole mass spectrometry operating in selected reaction monitoring mode. RESULTS: The assay validation showed a linear dynamic range up to 5 \ub5g/L or 200 pg/mg hair, inter- and intra-run precisions <6%, and accuracies within 5% of spiked concentrations. Limits of quantification were 0.001 \ub5g/L or 1 pg/mg hair for both TEB and PEN. Matrix effect experiments showed that the isotope dilution approach allowed for the control of bias sources. TEB and PEN were determined in hair of rats exposed to a low dose of TEB and in hair of agricultural workers exposed to TEB and/or PEN during the application season, indicating that both chemicals are incorporated into the hair upon exposure. CONCLUSIONS: The results of this study indicate that the developed assay is useful to evaluate the exposure to TEB and PEN in humans

Scavenging Capacity of Marine Carotenoids against Reactive Oxygen and Nitrogen Species in a Membrane-Mimicking System

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Carotenoid intake has been associated with the decrease of the incidence of some chronic diseases by minimizing the in vivo oxidative damages induced by reactive oxygen (ROS) and nitrogen species (RNS). The carotenoids are well-known singlet oxygen quenchers; however, their capacity to scavenge other reactive species, such as peroxyl radical (ROO center dot), hydroxyl radical (HO center dot), hypochlorous acid (HOCl) and anion peroxynitrite (ONOO-), still needs to be more extensively studied, especially using membrane-mimicking systems, such as liposomes. Moreover, the identification of carotenoids possessing high antioxidant capacity can lead to new alternatives of drugs or nutritional supplements for prophylaxis or therapy of pathological conditions related to oxidative damages, such as cardiovascular diseases. The capacity to scavenge ROO center dot, HO center dot, HOCl and ONOO- of seven carotenoids found in marine organisms was determined in liposomes based on the fluorescence loss of a fluorescent lipid (C-11-BODIPY581/591) due to its oxidation by these reactive species. The carotenoid-bearing hydroxyl groups were generally more potent ROS scavengers than the carotenes, whilst beta-carotene was the most efficient ONOO- scavenger. The role of astaxanthin as an antioxidant should be highlighted, since it was a more potent scavenger of ROO center dot, HOCl and ONOO- than alpha-tocopherol.10817841798Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Correlação da emissão diária de metano entérico e características de crescimento e eficiência alimentar de bovinos Nelore.

O objetivo deste trabalho foi avaliar as correlações entre a emissão diária de metano entérico (CH4) e características de crescimento e eficiência alimentar em bovinos Nelore com um ano de idade, previamente avaliados para o consumo alimentar residual (CAR). Foram testados 118 bovinos (56 fêmeas e 62 machos) nascidos em 2010, pertencentes à 30a progênie do rebanho Nelore Tradicional, provenientes do Centro APTA Bovinos de Corte-IZ/SP. O CAR foi estimado como o resíduo da equação de regressão do consumo de matéria seca sobre o peso metabólico e o ganho médio diário em teste pós-desmama de 107 e 112 dias de duração, para machos e fêmeas, respectivamente. Após o teste de desempenho, 46 animais (23 machos e 23 fêmeas) representativos das classes de alto CAR (>média + 0,5 DP; n= 23) e baixo CAR (<média ? 0,5 DP; n= 23), foram utilizados para estimar CH4 por meio da metodologia do gás traçador hexafluoreto de enxofre (SF6) com 7 dias Consecutivos de coleta. A emissão diária de metano está diretamente relacionada ao ganho médio diário e ao consumo de matéria seca. Não há evidências que a emissão diária de metano desses animais tenha relação com o consumo alimentar residual e a conversão alimentar

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

<p>Abstract</p> <p>Background</p> <p>Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy</p> <p>Objective</p> <p>To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.</p> <p>Methods</p> <p>A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks</p> <p>Results</p> <p>Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.</p> <p>Conclusion</p> <p>Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.</p