King-Smith, Christina, and Ivraym B. Barsoum. "Blebbistatin, a Myosin II Inhibitor, Blocks Melanosome Aggregation But Not Dispersion in Fish Retinal Pigment Epithelial (RPE) Cells." Molecular Biology of the Cell 14 Supp. (2003). Abstract.. ...
Blebbistatin is a small-molecule, high-affinity, noncompetitive inhibitor of myosin II. We have used negative staining electron microscopy to study the effects of blebbistatin on the organization of the myosin heads on muscle thick filaments. Loss of ADP and Pi from the heads causes thick filaments to lose their helical ordering. In the presence of 100 microM blebbistatin, disordering was at least 10 times slower. In the M.ADP state, myosin heads are also disordered. When blebbistatin was added to M.ADP thick filaments, helical ordering was restored. However, blebbistatin did not improve the order of thick filaments lacking bound nucleotide. Addition of calcium to relaxed muscle homogenates induced thick-thin filament interaction and filament sliding. In the presence of blebbistatin, filament interaction was inhibited. These structural observations support the conclusion, based on biochemical studies, that blebbistatin inhibits myosin ATPase and actin interaction by stabilizing the closed switch 2
Blebbistatin inhibits myosin ATPase activity and this way acto-myosin based motility. It binds halfway between the nucleotide binding pocket and the actin binding cleft of myosin, predominantly in an actin detached conformation.[10] This type of inhibition relaxes the acto-myosin myofilaments and leads to several biological effects. Blebbistatin inhibits the formation of blebs in melanoma cell culture,[11] hence its name. At a cellular level, blebbistatin also inhibits cytokinesis [11] and may also disrupt mitotic spindle formation.[12] Migration of cells can be either enhanced or inhibited depending on other conditions.[13] In neurons, blebbistatin was found to promote neurite outgrowth.[14] At the organ level blebbistatin stops the contraction of skeletal muscle [15] or heart muscle.[16] Blebbistatin has also been found to stabilize the super relaxed state in the myofilaments, where myosin heads are in a helical order and interact with each other but not with actin.[17][18][19] ...
During amoeboid locomotion, which many metazoan cells use to migrate through tissues, actin polymerization is thought to generate filopodia and lamellipodia at the leading edge, which move the cell forward. However, this model does not fully explain amoeboid movement - for example, why do some cells glide and others move jerkily? On p. 3833, Kunito Yoshida and Thierry Soldati propose that the focal production of blebs - transparent, spherical cell-surface protrusions - is also important for amoeboid locomotion. Blebs `blow out from the cell surface when myosin-II-driven contraction of the back of the cell increases the cytoplasmic fluid pressure. By visualizing the dynamics of F-actin, the authors show that migrating Dictyostelium cells continuously produce these blebs at the leading edge. Pseudopodia extension, cell-body retraction and the speed of cell locomotion are all reduced in myosin-II-null cells, cells treated with the myosin II inhibitor blebbistatin, and cells at high osmolarity - ...
TY - JOUR. T1 - Asenapine sensitization from adolescence to adulthood and its potential molecular basis. AU - Shu, Qing. AU - Qin, Rongyin. AU - Chen, Yingzhu. AU - Hu, Gang. AU - Li, Ming. PY - 2014/10/15. Y1 - 2014/10/15. N2 - Asenapine is a new antipsychotic drug that induces a long-lasting behavioral sensitization in adult rats. The present study investigated the developmental impacts of adolescent asenapine treatment on drug sensitivity and on 3 proteins implicated in the action of antipsychotic drugs (i.e. brain-derived neurotrophic factor (BDNF), dopamine D2 receptor, and δFosB) in adulthood. Male adolescent Sprague-Dawley rats (postnatal days, P 43-48) were first treated with asenapine (0.05, 0.10 or 0.20mg/kg, sc) and tested in the conditioned avoidance or PCP (2.0mg/kg, sc)-induced hyperlocomotion tasks for 5 days. After they became adults (~P 76), asenapine sensitization was assessed in a single avoidance or PCP-induced hyperlocomotion challenge test with all rats being injected with ...
购买(±)-Blebbistatin (CAS 674289-55-5), a potent, selective myosin II inhibitor。使用Abcam高品质的(±)-Blebbistatin帮助您更快取得科研成果。
A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells ...
For example, among those chemotherapeutic agents that work by inhibiting mitosis, many are effective anticancer agents because they interfere with microtubule function responsible for cell proliferation ( 17). However, microtubule disruption affects many important cellular processes including intracellular transport, maintenance of cell shape, cell signaling, and cell motility; therefore, the current antimitotic drugs suffer from serious side effects, including peripheral neuropathy ( 18). Work at the ICG has uncovered several new small molecules that disrupt additional key steps in cell division. The small molecules monastrol, blebbistatin, and binucleine 2 were discovered using cell-based phenotypic high-content screens ( 19), screens for non-muscle myosin II ATPase activity ( 20) and parallel RNAi and chemical genetic screens ( 21), respectively. As novel tools and lead compounds for biological study and pharmaceutical development, these compounds have the potential to evolve into ...
Both smooth muscle and nonmuscle myosin II activity is regulated by the phosphorylation state of the myosin regulatory light chain (MLC, MRLC, MLC20, Myl9). Phosphorylation of MLC at Thr-18 and Ser-19 activates myosin II motor activity and increases myosin filament stability. This activation has important roles in vari
Biochemical analysis in vertebrates suggests that RMLC phosphorylation on serine 19 (S19) triggers myosin II motor activity, and that phosphorylation on threonine 18 (T18) together with S19 further increases its activity (Ikebe et al., 1986). Likewise, phosphorylation of Drosophila RMLC at the position equivalent to S19 is sufficient to induce myosin II activity (Jordan and Karess, 1997; Vereshchagina et al., 2004). Consistent with these data, we show that a phosphomimetic variant of MLC-4/RMLC (MLC-4DD) fully rescues the elongation defect of mlc-4 mutants, whereas an unphosphorylatable form (MLC-4AA) fails to rescue the defect. Since the MLC-4T17A variant, which can still be phosphorylated on the adjacent serine (S18), rescued more significantly than the MLC-4S18A variant, we conclude that in C. elegans too, the serine plays a more crucial role in MLC-4/RMLC activation.. The kinase(s) that mediate RMLC phosphorylation during epithelial morphogenesis has not been systematically investigated ...
Development of versatile, chemically tunable photocages for photoactivated chemotherapy (PACT) represents an excellent opportunity to address the technical drawbacks of conventional photodynamic therapy (PDT) whose oxygen-dependent nature renders it inadequate in certain therapy contexts such as hypoxic tumors. As an alternative to PDT, oxygen free mechanisms to generate cytotoxic reactive oxygen species (ROS) by visible light cleavable photocages are in demand. Here, we report the detailed mechanisms by which the small molecule blebbistatin acts as a one-photon blue light-gated or two-photon near-infrared light-gated photocage to directly release a hydroxyl radical (•OH) in the absence of oxygen. By using femtosecond transient absorption spectroscopy and chemoselective ROS fluorescent probes, we analyze the dynamics and fate of blebbistatin during photolysis under blue light. Water-dependent photochemistry reveals a critical process of water-assisted protonation and excited state intramolecular
COA of Blebbistatin contains the actual results obtained from testing performed as part of quality control. View our Blebbistatin specific physical and chemical properties, and analytical data.
Buy Asenapine maleate (CAS 85650-56-2), an antipsychotic agent. Join researchers using high quality Asenapine maleate from Abcam and achieve your mission…
The purpose of this research study is to find out the potential benefits and safety of asenapine (Saphris®) in adults who suffer from the developmental form of stuttering.. It is hypothesized that individuals who are randomly assigned to asenapine will have an improvement in speech as compared to a placebo. ...
Most drug discovery efforts focus on generating inhibitors leading to loss-of-function phenotypes. My lab has been focusing on discovering ways to activate enzymes leading to gain-of-function phenotypes. Many enzymes such as proteases and kinases are stored in dormant "off" forms that are subsequently activated through post-translational modification. Work will be presented for discovery of small molecule activators for the apoptotic proteases known as caspases, as well a Ser-Thr kinase PDK-1. Our group is also developing split-proteins that can be activated by orthogonal small molecule dimerizers to phenocopy the effects seen from the small molecule activators. Such protein activators allow one to ignite signaling from specific nodes and thus probe the sufficiency of enzyme activity to drive a cellular response. Protein activation, as opposed to inhibition, expands the landscape for drug discovery.. Citation Format: James A. Wells, Dennis Wolan, Julie Zorn, Debajyoti Datta, Daniel Gray, Jack ...
DISCUSSION. Myosin RLC phosphorylation at Ser19 (P-RLC) is sufficient to fully activate SMMII and NMII (reviewed in [27]), however frequently observed RLC di-phosphorylation at Thr18/Ser19 (PP-RLC) (reviewed in [28]) may be responsible for prolonged myosin activation because of significantly slower RLC dephosphorylation [29]. Based on these findings, mono-phosphorylation at Ser19 and/or di-phosphorylation at Thr18/Ser19 are widely used to biochemically characterize myosin II motor activity and its involvement in (patho)physiological responses.. A variety of experimental approaches has been developed for analysis of P-RLC and PP-RLC. One of these approaches is electrophoretic separation of non-phosphorylated RLC, P-RLC, and PP-RLC followed by staining with a protein dye and densitometric analysis of the stained protein bands. RLC phospho-species can be separated by isoelectric focusing in the presence of pyrophosphate [9], urea/glycerol polyacrylamide electrophoresis [10], or recently introduced ...
Blebbistatin promotes OPC differentiation in vitro and increases the complexity of OL branching in cultures. (A) Purified OPC kept for 3 d in differentiation-pr
This trial, entitled "A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of Efficacy and Safety of Asenapine Compared with Placebo Using
SAPHRIS® (asenapine) indication, dosing, side effects, & more. See Important Safety Information & full Prescribing Information, including Boxed Warning.
This trial will compare the efficacy and tolerability of different doses of asenapine [SCH 900274; Schering-Plough] (5 and 10mg twice-daily) in patients with an
UPDATED: 07.29.09 @ 7:05 PM EDT -- At least one MSM news outlet is showing the beginnings of covering both sides of the Saphris (asenapine) FDA story. Well, its a small start -- but a welcome one -- and in Greece, of all places. Much more from the cogent keyboard of Salmon, tonight: . .…
Asenapine- యొక్క ఉపయోగాలు, మోతాదు, దుష్ప్రభావాలు, ప్రయోజనాలు, పరస్పర చర్యలు మరియు హెచ్చరికను కనుగొనండి
NKTR-102 (etirinotecan pegol, also known as ONZEALD TM ) is our next-generation topoisomerase I inhibitor proprietary drug candidate. In 2015, we announced topline data from a Phase 3 clinical study for NKTR-102, which we call the BEACON study (BrEAst Cancer Outcomes with NKTR-102), as a single-agent therapy for women with advanced metastatic breast cancer. The BEACON study compared NKTR-102 to an active control arm comprised of a single chemo therapy agent of physicians choice (TPC) in patients who were heavily pre-treated with a median of three prior therapies for metastatic disease. In a topline analysis of 852 patients from the trial, NKTR-102 provided a 2.1 month improvement in median ove rall survival (OS) over TPC (12.4 months for patients receiving NKTR-102 compared to 10.3 months for patients receiving TPC). Based on a stratified log-rank analysis, the primary endpoint measuring the Hazard Ratio (HR) for survival in the NKTR-102 group compared to the active control arm was 0.87 with a ...
Introduction: Talazoparib (BMN 673) is a highly potent and specific PARP1/2 inhibitor (PARPi) that has demonstrated significant clinical activity in patients with germline BRCA mutation ovarian and breast cancer, as well as in patients with small cell lung cancer. Non-clinically, combination of PARPi, including talazoparib, with Topoisomerase 1 (Top1) inhibitors, such as irinotecan, has shown synergy in BRCA1 mutant MX-1 model (Shen et al. 2013; Hoch et al., NCI-AACR-EORTC 2014). Etirinotecan pegol (NKTR-102, pegylated irinotecan) is a long-acting Top1 inhibitor, designed to provide extended drug exposure to the tumor. In preclinical models, NKTR-102 has improved efficacy and tolerability over irinotecan. We therefore hypothesized that the combination of talazoparib with NKTR-102 would be well tolerated and harness the full synergistic potential of combined Top1 and PARP inhibition.. Method: In tolerability studies, three dose levels of talazoparib (0.1, 0.2 and 0.3 mg/kg, QDx14) given with ...
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450:712-16 ...
Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2060-8. Epub 2008 Feb 22. Blebbistatin inhibits the chemotaxis of vascular smooth muscle cells by disrupting the myosin II-actin interaction. Wang HH, Tanaka H, Qin X, Zhao T, Ye LH, Okagaki T, Katayama T, Nakamura A, Ishikawa R, Thatcher SE, Wright GL, Kohama K.. ...
The Dodge Charger SRT Hellcat and Nissan GT-R couldnt be more different. Ones a rear-wheel-drive sedan powered by a supercharged V-8 while the other is an all-wheel-drive sports car with turboch...
For the study, which was supported by Allergan affiliate Forest Laboratories, adults with bipolar I disorder who were experiencing an acute manic or mixed episode were enrolled in a randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg twice-a-day in the open-label period but could be titrated down to 5 mg. After completing the open-label period, subjects meeting stabilization/stable-responder criteria (based on Young Mania Rating Scale [YMRS] and Montgomery-Åsberg Depression Rating Scale [MADRS] scores ≤12) were randomized to asenapine or placebo treatment in the double-blind period. ...
This medication is used to treat certain mental/mood disorders (such as schizophrenia, bipolar disorder). Asenapine helps you to think more clearly, f
A synthesis of L,L-N,N-dimethylcycloisodityrosine (I) based on an intramol. SNAr reaction is reported. A possible explanation was proposed to account for the facile epimerization encountered in the cycloetherification of dipeptide L,L-II and a soln. to this problem led to a formal total synthesis of deoxybouvardin. [on SciFinder (R)] Bigot, Antony; Beugelmans, Rene; Zhu, Jieping
The Y-MRS assesses the severity of manic episodes by assigning a severity rating to each of 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight). Seven of the 11 items are rated on a scale of 0-4, and 4 of the items are rated on a scale of 0-8. The Y-MRS total score, observed cases (OC), the assessment closest to the scheduled assessment day within the allowed window, is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. Improvement in symptoms is represented by change from baseline values that are negative ...
Adherent cells balance adhesion to their substrate against contractile force acting on the cytoskeleton. But can tipping this balance affect a cells fate? To find out, Dennis Discher and coworkers have examined how contractility affects the development of skeletal muscle myocytes (p. 5855). They culture myocytes on micropatterned slides containing thin rectangles of collagen substrate. This forces the myocytes to form linear rather than branched myotubes, which allows the authors to measure their contractility by seeing how much they shorten when one end is detached from the substrate. Interestingly, myotubes attached directly to the substrate do not differentiate properly, failing to generate the striations characteristic of skeletal muscle. By contrast, cells on top of this lower layer do become striated. Discher and co-workers correlate this with greater contractility of the upper-layer cells. They use an inhibitor of myosin II (blebbistatin) to show that this motor is the source of the ...
Organon achieves milestone in asenapine development. In the past, weve reported on the development of Asenapine: a drug which is supposed to treat psychotic and mood disorders. Recently, it seems that Organon ( Akzo Nobel ), the company responsible for asenapine "has achieved a development milestone for (the drug)..." This "milestone has resulted in a retroactive change in the division of full Phase III development costs, with the co-collaborator, Pfizer , increasing its (asenapines) share; the agreed future revenue sharing will remain in place. The milestone, which relates to satisfactory results in the companies clinical trial programme and the achievement of it, of which no further specifics were disclosed, reconfirms the commitment of both companies to fully explore the clinical potential of asenapine.". Though early clinical trials demonstrate that Asenapine will "restore balance to a patients life through superior releif of negative symptoms," its important to wait for further results ...
Learn about Saphris (Asenapine Sublingual Tablets) may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling, reviews, and related medications.
Grimm, C., J rs, S., Saldanha, S.A., Obukhov, A.G., Pan, B., Oshima, K., Cuajungco, M.P., Chase, P., Hodder, P., and Heller, S. (2010). Small molecule activators of TRPML3. Chemistry and Biology, 17, 135-148. NCBI link Samie M.A.*, Grimm C., Evans J.E.#, Curcio-Morelli, C., Heller, S., Slaugenhaupt, S.A. and Cuajungco, M.P. (2009) The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by the presence of TRPML1. Pfl gers Archiv European Journal of Physiology, 459, 79-91 NCBI link (http://www.ncbi.nlm.nih.gov/pubmed/19763610). #Undergraduate student, *Graduate student. Cuajungco, M.P. and Samie, M.A.* (2008) The varitint-waddler mouse phenotypes and the TRPML3 mutation: cause and consequence. Pfl gers Archiv European Journal of Physiology, 457, 463-473. *Graduate student. NCBI link (http://www.ncbi.nlm.nih.gov/pubmed/18504603?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) D`hoedt, D., Owsianik, G., Prenen, J., ...
Perophoramidine 1 is a halogenated natural product which contains two contiguous quaternary centres within its structure. In this thesis, approaches towards the synthesis of perophoramidine are described. In particular, the synthesis of the tetracyclic core structure and the formation of the quaternary centres have been examined. In Chapter 1, the natural product perophoramidine 1 is introduced and its isolation, structure and biological activity is discussed. The structurally related communesin family of natural products are also introduced before the literature published on both the biosynthesis and laboratory synthesis of perophoramidine 1, is reviewed. Finally the Westwood groups approach towards the synthesis of perophoramidine 1 is introduced with a summary of non-halogenated model system investigations previously carried out within the group being provided. Chapter 2 describes studies towards the synthesis of an appropriately halogenated indolo[2,3-b]quinoline core structure of ...
21. A method of treating or ameliorating a cell proliferative disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I): ##STR00156## or a pharmaceutically acceptable salt or conjugate thereof; wherein R1 is H, or C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C5-C6 aryl, C6-C12 arylalkyl, or a heteroform of one of these, each of which may be optionally substituted; R2 is H, or C1-C8 alkyl, C1-C8 heteroalkyl, C6-C14 arylalkyl, C6-C14 heteroarylalkyl, each of which may be optionally substituted; or R1 and R2 may be taken together with the atoms to which they are attached to form an optionally substituted 5- to 7-membered azacyclic ring, optionally containing an additional heteroatom selected from N, O, and S as a ring member; R4 is H, or C1-C4 alkyl; R5 is H, or C1-C8 alkyl, C2-C12 alkenyl, C3-C8 cycloalkyl, C4-C12 cycloalkylalkyl, C2-C12 alkynyl, C6-C12 aryl, C6-C14 arylalkyl, alkylsulfonyl, or arylsulfonyl, or a heteroform of one ...
InChI=1/C40H34Cl2N6O6/c1-15(2)27-37-46-29-32(54-37)40-20-9-5-8-19(18-7-6-10-22-25(18)26(33(41)43-22)31-34(42)48-38(29)53-31)28(20)47-39(40)52-24-12-11-17(13-21(24)40)14-23(35(50)45-27)44-36(51)30(49)16(3)4/h5-13,15-16,23,27,30,39,43,47,49H,14H2,1-4H3,(H,44,51)(H,45,50)/t23-,27-,30-,39-,40u /m0/s1/f/h44-45HÂ ChemSpider CID: 10478902Â InChI=1/C40H34Cl2N6O6/c1-15(2)27-37-46-29-32(54-37)40-20-9-5-8-19(18-7-6-10-22-25(18)26(33(41)43-22)31-34(42)48-38(29)53-31)28(20)47-39(40)52-24-12-11-17(13-21(24)40)14-23(35(50)45-27)44-36(51)30(49)16(3)4/h5-13,15-16,23,27,30,39,43,47,49H,14H2,1-4H3,(H,44,51)(H,45,50)/t23?,27-,30-,39?,40-/m0/s1/f/h44-45H Â ChemSpider CID: 17212293Â InChI=1/C40H34Cl2N6O6/c1-15(2)27-37-46-29-32(54-37)40-20-9-5-8-19(18-7-6-10-22-25(18)26(33(41)43-22)31-34(42)48-38(29)53-31)28(20)47-39(40)52-24-12-11-17(13-21(24)40)14-23(35(50)45-27)44-36(51)30(49)1 6(3)4/h5-13,15-16,23,27,30,39,43,47,49H,14H2,1-4H3,(H,44,51)(H,45,50)/t23-,27+,30+,39-,40+/m1/s1Â Totally ...
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Looking for online definition of myosin heavy chain IIa in the Medical Dictionary? myosin heavy chain IIa explanation free. What is myosin heavy chain IIa? Meaning of myosin heavy chain IIa medical term. What does myosin heavy chain IIa mean?
Saphris (asenapine) is used for the treatment of schizophrenia and bipolar I disorder. Saphris information includes news, clinical trial results and side effects.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
... N. Martin, M. Deutsch, F. Bert, D. Andreica, A. Amato, P. Bonfa, R. De Renzi, U. K. Roessler, P. Bonville, L. N. Fomicheva, A. V. Tsvyashchenko, and I. Mirebeau Phys. Rev. B 93 (2016) 174405. We have studied by muon spin resonance the helical ground state and fluctuating chiral phase recently observed in the MnGe chiral magnet. At low temperature, the muon polarization shows double-period oscillations at short-time scales. Their analysis, akin to that recently developed for MnSi [A. Amato et al., Phys. Rev. B 89, 184425 (2014)], provides an estimation of the field distribution induced by the Mn helical order at the muon site. The refined muon position agrees nicely with ab initio calculations. With increasing temperature, an inhomogeneous fluctuating chiral phase sets in, characterized by two well-separated frequency ranges which coexist in the sample. Rapid and slow fluctuations, respectively,
Mulungu bark is an herbal therapy, used mostly in Brazil, for mood disorders. Here we take a look at the research supporting mulungu bark for mental health.
BACLOFEN AND ACAMPROSATE BASED THERAPY OF NEUROLOGICAL DISORDERS | INJECTABLE FORMULATIONS OF ASENAPINE | SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF | TRYPTAMIDE COMPOSITIONS AND METHODS OF USE | A COMPOSITION FOR THE PREVENTION AND TREATMENT OF METABOLIC DISORDERS ASSOCIATED WITH MENOPAUSE AND CLIMACTERIC |
For muscle car purists, the four-door Charger in Hemi-less form is a disgrace to the legacy of the cars heritage. However, even the most traditional mopar lovers have to bow down to the power that is the Charger SRT8.. The already sharp looking Charger sedan receives an AutoStick five-speed automatic transmission, 20-inch alloy wheels with performance tires, sport suspension, dual chrome exhaust pipes, plus aerodynamic body kit with hood scoop and rear spoiler. But all the extra accoutrements that may accompany the SRT8 are secondary to the 6.1 liter SRT Hemi V8 engine that is at the heart of this beast. Producing an enormous 425 horsepower and 420 pound-feet of torque, it is almost an overwhelming powerplant in this car. Same thing could be said for the sound and exhaust which effectively communicates to anyone who dares approach what is under the hood. The payoff for owning the SRT8 is a top speed of 165 mph and a 0 to 60 mph time under five seconds. No small feat givn its weight of nearly ...
渗出型老年性黄斑变性(wAMD)以脉络膜新生血管(CNV)的进行性生长为主要特征。抗血管内皮生长因子(VEGF)药物在控制CNV的发展和改善视功能中已取得一定成果,但其仍存在频繁注射、容易耐药等不足。放射治疗(放疗)可使局部炎症细胞群失效,CNV在无周细胞覆盖下不稳定且无VEGF存在,血管内皮细胞被诱导凋亡。因此,放疗被认为是抗VEGF治疗的一类潜在辅助治疗手段。目前临床试验治疗wAMD主要运用黄斑前近距离放疗和远距离立体定向放疗(SRT)。其中,SRT或许可作为接受抗VEGF治疗患者的首选辅助治疗方式。了解放疗用于wAMD治疗的进展,可为wAMD的临床研究提供参考。
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Special Relativity Theory (SRT) is considered to be compatible with classical electrodynamics. However, there are several logically deduced discrepancies inherent in SRT itself, which are called
TY - JOUR. T1 - Smooth muscle myosin expression, isoform composition, and functional activities in rat corpus cavernosum altered by the streptozotocin-induced type 1 diabetes. AU - Zhang, Xinhua. AU - Kanika, Nirmala D.. AU - Melman, Arnold. AU - DiSanto, Michael E.. PY - 2012/1. Y1 - 2012/1. N2 - Diabetes mellitus (DM) is a quite common chronic disease, and the prevalence of erectile dysfunction (ED) is three times higher in this large population. Although diabetes-related ED has been studied extensively, the actin-myosin contractile apparatus was not examined. The mRNAs encoding smooth muscle myosin (SMM) heavy chains (MHC) and essential light chains (LC 17) exist as several different alternatively spliced isoforms with distinct contractile properties. Recently, we provided novel data that blebbistatin (BLEB), a specific myosin II inhibitor, potently relaxed corpus cavernosum smooth muscle (CCSM). In this study, we examine whether diabetes alters SMM expression, alternative splicing, and/or ...