Boswellia carteri and Boswellia serrata (Indian olibanum)
Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.
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provides coniferyl ferulate(CAS#:22419-74-5) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
The cascade of events that lead to cognitive decline, motor deficits, and psychiatric symptoms in patients with Huntington disease (HD) is triggered by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein. A significant mechanism in HD is the generation of mutant HTT fragments, which are generally more toxic than the full-length HTT. The protein fragments observed in human HD tissue and mouse models of HD are formed by proteolysis or aberrant splicing of HTT. To systematically investigate the relative contribution of the various HTT protein proteolysis events observed in vivo, we generated transgenic mouse models of HD representing five distinct proteolysis fragments ending at amino acids 171, 463, 536, 552, and 586 with a polyglutamine length of 148. All lines contain a single integration at the ROSA26 locus, with expression of the fragments driven by the chicken β-actin promoter at nearly identical levels. The transgenic mice N171-Q148 and N552-Q148 display significantly accelerated phenotypes and a shortened life span when compared with N463-Q148, N536-Q148, and N586-Q148 transgenic mice. We hypothesized that the accelerated phenotype was due to altered HTT protein interactions/complexes that accumulate with age. We found evidence for altered HTT complexes in caspase-2 fragment transgenic mice (N552-Q148) and a stronger interaction with the endogenous HTT protein. These findings correlate with an altered HTT molecular complex and distinct proteins in the HTT interactome set identified by mass spectrometry. In particular, we identified HSP90AA1 (HSP86) as a potential modulator of the distinct neurotoxicity of the caspase-2 fragment mice (N552-Q148) when compared with the caspase-6 transgenic mice (N586-Q148).
caspase, neurodegenerative disease, polyglutamine disease, proteolysis, transgenic mice
Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo*
Robert O'Brien,‡ Francesco DeGiacomo,‡ Jennifer Holcomb,‡ Akilah Bonner,‡ Karen L. Ring,‡ Ningzhe Zhang,‡ Khan Zafar,‡ Andreas Weiss,§ Brenda Lager,¶ Birgit Schilling,‡ Bradford W. Gibson,‡ Sylvia Chen,‡ Seung Kwak,¶ and Lisa M. Ellerby‡,1
2015 Jul 31
Axon degeneration is a programed process that takes place during development, in response to neuronal injury, and as a component of neurodegenerative disease pathology, yet the molecular mechanisms that drive this process remain poorly defined. In this study, we have developed a semi-automated, 384-well format axon degeneration assay in rat dorsal root ganglion (DRG) neurons using a trophic factor withdrawal paradigm. Using this setup, we have screened a library of known drugs and bioactives to identify several previously unappreciated regulators of axon degeneration, including lipoxygenases. Multiple structurally distinct lipoxygenase inhibitors as well as mouse DRG neurons lacking expression of 12/15-lipoxygenase display protection of axons in this context. Retinal ganglion cell axons from 12/15-lipoxygenase-null mice were similarly protected from degeneration following nerve crush injury. Through additional mechanistic studies, we demonstrate that lipoxygenases act cell autonomously within neurons to regulate degeneration, and are required for mitochondrial permeabilization and caspase activation in the axon. These findings suggest that these enzymes may represent an attractive target for treatment of neuropathies and provide a potential mechanism for the neuroprotection observed in various settings following lipoxygenase inhibitor treatment.
axon degeneration, DRG, lipoxygenase, NGF
Identification of 12/15-Lipoxygenase as a Regulator of Axon Degeneration through High-Content Screening
York Rudhard,corresponding author1,* Arundhati Sengupta Ghosh,2,* Beatrix Lippert,1 Alexander Bocker,1 Mehdi Pedaran,1 Joachim Kramer,1 Hai Ngu,3 Oded Foreman,3 Yichin Liu,4 and Joseph W. Lewcockcorresponding author2
2015 Feb 18
Data of the Central Bureau of Statistic of Nepal from 2008 show a total of more than 46,000 illegal drug users, out of which 61% are injecting drug users (IDU). An injecting mix of medicines like opioids, benzodiazepines and antihistamines (the so-called South Asian cocktail) was prevalent. Furthermore, it is estimated that about 70,000 people are living with human immunodeficiency virus (HIV). The government of Nepal has started realizing and recognizing drug use and HIV as significant health and social issues. Harm reduction programs such as needle syringe exchange and opioid substitution treatment are being implemented.
The aim of this study is to obtain specific knowledge on the drug use behaviour and the health status of drug users with a focus on HIV in drug users with concurrent injection of opioids, benzodiazepines and antihistamines. After an initial mapping of Kathmandu Valley, 300 drug users in contact with different treatment and counselling centres were randomly chosen for the interviews. The research questionnaire was designed according to the European Addiction Severity Index (EuropASI) and Maudsley Addiction Profile standards.
Ninety-one percent of the respondents are male and 9% female. Mean age is 28.7 years. Ninety-five percent are injecting drug users with a mean of 8.7 years of drug use history. Eighty-six percent are injecting different ‘cocktails’, usually made of buprenorphine, diazepam, promethazine and/or other substances (30-day prevalence). Similarly, 48% use heroin, whereas only 2% take cocaine/crack. Among those tested for HIV (N = 223), 33% are positive (25% of the sample population). Compared to the other drug users (mainly heroin), the cocktail users show a higher HIV infection rate and more co-infections. Furthermore, risk behaviour, as e.g. needle sharing, is much more common among the cocktail users.
Currently, the mixture of medicines, opioids, benzodiazepines and antihistamines, is the predominant drug in Nepal; the pharmaceutical drugs needed to prepare the cocktail are less expensive than heroin and relatively easy to acquire. The cocktail users show a higher risk behaviour regarding the transmission of HIV than heroin drug users. It needs to be considered which HIV prevention measures are necessary to target the specific needs of drug users who inject a mixture of opioids, benzodiazepines and antihistamines, since the available services (such as needle syringe exchange) do not seem to cover their specific needs (high percentage of needle sharing).
Opiates, Benzodiazepines, Antihistamines, South Asian cocktail, Opioid substitution treatment, HIV, Buprenorphine (injectable)
‘South Asian cocktail’ - the concurrent use of opioids, benzodiazepines and antihistamines among injecting drug users in Nepal and associations with HIV risk behaviour
Saroj Prasad Ojha,1 Suraj Sigdel,2 Hans-Gunter Meyer-Thompson,3 Harald Oechsler,4 and Uwe Vertheincorresponding author4