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91.
92.
As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies. 相似文献
93.
《Anaesthesia and Intensive Care Medicine》2014,15(5):221-224
Transtracheal jet ventilation is a technique for ventilation of apnoeic lungs. This article outlines the indications, equipment required, insertion technique and complications of transtracheal jet ventilation. It can be used electively to aid management of the difficult airway and for laryngeal surgery. It also has a vital role in the management of the ‘can't intubate – can't ventilate’ scenario. Death and hypoxic brain damage under anaesthesia are fortunately rare, but most commonly occur as a result of problems with tracheal intubation. No patient should suffer hypoxic brain damage without an attempt at transtracheal ventilation being made. 相似文献
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95.
Context: Protection of neurons from degeneration is an important preventive strategy for dementia. Much of the dementia pathology implicates oxidative stress pathways. Turmeric (Curcuma longa L.) contains curcuminoids which has anti-oxidative and neuro-protective effects. These effects are considered to be similar to those of citicoline which has been regularly used as one of standard medications for dementia.Objective: This study aimed at investigating the effects of turmeric rhizome extract on the hippocampus of trimethyltin (TMT)-treated Sprague-Dawley rats.Materials and methods: The rats were divided randomly into six groups, i.e., a normal control group (N); Sn group, which was given TMT chloride; Sn-Cit group, which was treated with citicoline and TMT chloride; and three Sn-TE groups, which were treated with three different dosages of turmeric rhizome extract and TMT chloride. Morris water maze test was carried out to examine the spatial memory. The estimated total number of CA1 and CA2–CA3 pyramidal cells was calculated using a stereological method.Results: The administration of turmeric extract at a dose of 200?mg/kg bw has been shown to prevent the deficits in the spatial memory performance and partially inhibit the reduction of the number of CA2–CA3 regions pyramidal neurons.Discussion: TMT-induced neurotoxic damage seemed to be mediated by the generation of reactive oxygen species and reactive nitrogen species. Turmeric extract might act as anti inflammatory as well as anti-oxidant agent.Conclusions: The effects of turmeric extract at a dose of 200?mg/kg bw seem to be comparable to those of citicoline. 相似文献
96.
Partition coefficients between human stratum corneum lipids and water (Ksclip/w) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model (Hansen et al., Adv Drug Deliv Rev. 2013;65(2):251-264). An additional datum for water itself in porcine SC that considerably extends the molecular size and lipophilicity range of the data set is considered. The data are analyzed in terms of an extended linear free energy relationship involving octanol/water partition coefficients, Abraham solvation parameters, and a secondary, power law molecular weight dependence. The optimum fit to log Ksclip/w for the full data set reduces the standard error of prediction from 0.50 for a Hansen-like model to 0.39; corresponding multiplicative errors in Ksclip/w are reduced from a factor of 3.1 to one of 2.5. The difference in performance is driven by the water datum, which requires a more complex dependence on molecular size than that afforded by Abraham parameters. In the absence of the water value, the Hansen-like model, which does not include a dependence on molecular size, is essentially optimum. A comparison is presented to fluid-phase phospholipid–water systems, which have a demonstrably different structure–property relationship. 相似文献
97.
A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product. 相似文献
98.
Tereza Zelenková Maria Julia Mora Antonello A. Barresi Gladys Ester Granero Davide Fissore 《Journal of pharmaceutical sciences》2018,107(4):1157-1166
This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jet reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, for example, polycaprolactone, is required to support chitosan to obtain a monomodal particle size distribution, with low particle diameters. A surfactant is required to reduce the nanoparticle size (down to a mean diameter of about 260 nm) and obtain a positive zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg mL?1) and of chitosan (in the range 1.5-5 mg mL?1) on both the mean particle size and zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min?1 is required in the considered reactor to minimize the particle size. 相似文献
99.
Joanne Heade Sam Maher Sinead B. Bleiel David J. Brayden 《Journal of pharmaceutical sciences》2018,107(6):1648-1655
In addition to their solubilizing properties, excipients used in lipid-based formulations can improve intestinal permeability of macromolecules. We determined whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a lipoidal excipient (Labrasol®) could potentiate transepithelial flux of a poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4]) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C10), sodium undecylenate (C11:1), or sodium laurate (C12) combined with Labrasol® increased the apparent permeability coefficient (Papp) of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol® alone. For example, combination of C11:1 (0.5 mg/mL) with Labrasol® (1 mg/mL) increased the Papp of FD4 by 10- and 11-fold over the respective individual agents at the same concentrations where no enhancement was evident. The increased enhancement ratios seen with the combinations were associated with some perturbation in intestinal histology and with attenuation of an epithelial functional measure, carbachol-stimulated inward short-circuit current. In conclusion, combining three MCFAs separately with Labrasol® increased the Papp of FD4 to values greater than those seen for MCFAs or Labrasol® alone. Ultimately, this may permit lower concentrations of MCFA to be used in combination with other excipients in oral formulations of poorly permeable molecules. 相似文献
100.
Sara Matić Milena Jadrijević-Mladar Takač Monika Barbarić Bono Lučić Koraljka Gall Trošelj Višnja Stepanić 《Journal of pharmaceutical sciences》2018,107(11):2957-2964
The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B. 相似文献