Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2-/- mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/-, and DP1-/- mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP-/- mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.
The eukaryotic muscular expression vector VR1012/TPO was constructed with human recombinant TPO cDNA as the therapy gene to transfect the CHO cell and directly inject it to BALB/C mouse. CHO cells could be transferred with VR/TPO and highly express TPO protein. VR/TPO was found to promote megakaryocytics in BALB/C mouse.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The Musca domestica is a serious hygienic pest of poultry, humans, and livestock facilities with the immense ability for resistance development against chemical insecticides.The current study aimed to evaluate the susceptibility and resistance status of M. domestica against different classes of insecticides.For this purpose, adult M. domestica populations were collected from five different localities of Sargodha division (Sargodha, Khushab, Jauharabad, Mianwali, and Bhakkar), Punjab, Pakistan, and tested against selected insecticides.The resistance ratios (RR) at LC 50 ranged from 10.32-35.37 folds for deltamethrin, 17.49-38.13folds for fipronil, and 10.70-18.81folds for chlorpyrifos.The RR values at LC 50 for imidacloprid and pyriproxyfen ranged from 4.35-28.0and 10.56-21.45folds, respectively.The study showed varying levels of resistance in M. domestica populations from area to area and from insecticide to insecticide.Therefore, to control resistance development in M. domestica from livestock facilities, inappropriate and excessive use of insecticides must be controlled through proper mechanisms and strategies.
Background: A novel series of s-tetrazine derivatives was designed as a new scaffold and synthesized efficiently as VEGFR-2 inhibitors for the first time. Methodology & results: The inhibitory activities of the new compounds were tested by MTT assay and enzyme assay, respectively. Western blot assay, cell apoptosis assay and cell migration assay were carried out to study the action mechanism of them. All the synthesized compounds showed evident VEGFR-2 inhibitory activities (IC50 in the range of 88.53–257.55 nM). Compounds 23h, 25d, 26e and 27c showed excellent anti-proliferative activities against the four tested cell lines and were better than sorafenib basically. Conclusion: Compounds with good activities based on this novel scaffold can be screened successfully.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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