In situ transmission electron microscopy studies of shear bands in a bulk metallic glass based composite

In situ straining transmission electron microscopy (TEM) experiments were performed to study the propagation of the shear bands in the Zr56.3Ti13.8Cu6.9Ni5.6Nb5.0Be12.5 bulk metallic glass based composite. Contrast in TEM images produced by shear bands in metallic glass and quantitative parameters of the shear bands were analyzed. It was determined that, at a large amount of shear in the glass, the localization of deformation occurs in the crystalline phase, where formation of dislocations within the narrow bands are observed

7‑hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects

Mitragynina speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine, and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.</p

Population of the republic of belarus on age and marital status

In this paper the structure and dynamics of marital status has been analyzed. The data of two last ensuses in Belaus have been compared

Dislocations in a multiphase Ni-Al-Fe alloy

SIGLEAvailable from British Library Document Supply Centre-DSC:8019.322(92691) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Methods of Determining Creep, Long-Term Strength and Compressibility Characteristics of Frozen Soils

Frozen soils consisting of ice and unfrozen water possess clearly defined rheological properties. The evaluation of strength involves determining the load at which, over a given period of time, a state of equilibrium exists, which, if exceeded, causes failure. When evaluating frozen soils for deformation the load calculated is that at which the deformation reached is the maximum permissible for the structure. Equations are developed that give deformation patterns for frozen soil. Frozen soil testing for deformation may be conducted with both disturbed and undisturbed samples but the soil temperatures must be kept constant. The main features of creep curves are obtained from compression tests in the laboratory on a series of similar samples. Results are plotted of time versus deformation. At large loads an S-shaped curve is obtained showing a large deformation with complete failure occurring in a short time. For intermediate loads there is again the instantaneous deformation, followed by a very small deformation with time but at the end deformation accelerates and failure ensues. For smaller loads the instantaneous deformation occurs but this is followed by a very long period of very small or no deformation. The nature of the curves for any moment of time depends on soil type but the general pattern always remains the same. Usually an exponential relationship is assumed.SOMMAIRE FRANCAIS A SUIVREPeer reviewed: NoNRC publication: Ye

7-Hydroxymitragynine is an Active Metabolite of Mitragynine and a Key Mediator of its Analgesic Effects

Mitragynina speciosa, more commonly known as kratom, is a plant native to Southeast Asia, the leaves of which have been used traditionally as a stimulant, analgesic, and treatment for opioid addiction. Recently, growing use of the plant in the United States and concerns that kratom represents an uncontrolled drug with potential abuse liability, have highlighted the need for more careful study of its pharmacological activity. The major active alkaloid found in kratom, mitragynine, has been reported to have opioid agonist and analgesic activity in vitro and in animal models, consistent with the purported effects of kratom leaf in humans. However, preliminary research has provided some evidence that mitragynine and related compounds may act as atypical opioid agonists, inducing therapeutic effects such as analgesia, while limiting the negative side effects typical of classical opioids. Here we report evidence that an active metabolite plays an important role in mediating the analgesic effects of mitragynine. We find that mitragynine is converted in vitro in both mouse and human liver preparations to the much more potent mu-opioid receptor agonist 7-hydroxymitragynine, and that this conversion is mediated by cytochrome P450 3A isoforms. Further, we show that 7-hydroxymitragynine is formed from mitragynine in mice and that brain concentrations of this metabolite are sufficient to explain most or all of the opioid-receptor-mediated analgesic activity of mitragynine. At the same time, mitragynine is found in the brains of mice at very high concentrations relative to its opioid receptor binding affinity, suggesting that it does not directly activate opioid receptors. The results presented here provide a metabolism-dependent mechanism for the analgesic effects of mitragynine and clarify the importance of route of administration for determining the activity of this compound. Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.</p