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61.
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Nanda NC Samal AK Bakir S Moursi M Thakur AC Aggarwal R Singh S Soto B Cerfolio R McGiffin DC 《Echocardiography (Mount Kisco, N.Y.)》1998,15(4):409-417
We present the transesophageal echocardiographic findings in two adult patients with right-sided aortic arch: one without dissection and the other with traumatic aortic injury (dissection). In both patients, the branching pattern was the left common carotid artery and then the right common carotid artery, followed by the right and left subclavian arteries. The technique for the diagnosis of this anomaly and the identification of adjacent vascular structures using contrast echocardiography is described. Three-dimensional reconstruction of the aortic arch also was performed in both patients. 相似文献
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64.
Thomas J. Wilson Aditya S. Pandey William R. Stetler Jr. Matthew C. Davis David A. Giles Neeraj Chaudhary Joseph J. Gemmete B. Gregory Thompson 《Acta neurochirurgica》2014,156(5):855-859
Background
Thromboembolic events represent a clinically significant cause of neurological morbidity during the endovascular management of cerebral aneurysms. We have implemented an anti-thromboembolic regimen consisting of pre- and postoperative dual antiplatelet therapy, as well as postoperative anticoagulation using heparin and dextran. The aims of our study were to examine the effect of this regimen on thromboembolic rates during elective aneurysm coiling, and to elucidate risk factors associated with the development of thromboembolic events in this setting.Methods
We conducted a retrospective review of patients who underwent elective intracranial aneurysm coiling between January 2005 and February 2012. The primary outcome of interest was the occurrence of a clinically significant peri-procedural thromboembolic event. Secondary outcomes included the occurrence of a central nervous system (CNS) or systemic hemorrhage.Results
During the study period, 312 patients underwent elective aneurysm coiling and six (2 %) thromboembolic events occurred; three (1 %) occurred in the group that received the anti-thromboembolic regimen (261 patients) and three (6 %) occurred in the group that did not receive the regimen (51 patients), resulting in a statistically significant difference (P?=?0.024). Both the presence of a hypercoagulable state (P?=?0.014) and the lack of the anti-thromboembolic regimen (P?=?0.043) were significantly associated with the occurrence of a thromboembolic event.Conclusions
This study provides evidence that the regimen described here is safe and reduces thromboembolic complications during elective aneurysm coiling. Ours is likely the most aggressive regimen in the published literature and significantly reduced the rate of thromboembolism without any significant increase hemorrhagic complications. 相似文献65.
66.
Aditya V. Gandhi Theodore W. Randolph John F. Carpenter 《Journal of pharmaceutical sciences》2019,108(6):1973-1983
The impact of drug conjugation on intra- and intermolecular interactions of trastuzumab (TmAb) was determined by comparing the conformational and colloidal stabilities of TmAb and trastuzumab emtansine (T-DM1). In low ionic strength formulations, drug conjugation to native lysine residues of TmAb significantly reduced the repulsive electrostatic interactions between T-DM1 molecules. When these electrostatic interactions were screened in solutions with high ionic strength, intermolecular interactions between T-DM1 molecules were found to be more attractive than those between TmAb molecules. Drug conjugation lowered the colloidal stability of T-DM1 compared to TmAb, making T-DM1 more susceptible to agitation-induced aggregation. The presence of polysorbate-20 in the formulations inhibited aggregation of TmAb and T-DM1 induced by the hydrophobic air-water interface. Furthermore, the effect of increased hydrophobic interactions between T-DM1 molecules was studied by monitoring aggregation in TmAb and T-DM1 solutions that were incubated at 4°C, 25°C, and 50°C. Conjugating DM1 to TmAb increased the hydrophobicity of the molecule, and faster aggregation of T-DM1 at 50°C could be attributed to a temperature-dependent increase in hydrophobic interactions between T-DM1 molecules. 相似文献
67.
Anna N. Bukiya Guruprasad Kuntamallappanavar Justin Edwards Aditya K. Singh Bangalore Shivakumar Alex M. Dopico 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(25):9313-9318
Ethanol alters BK (slo1) channel function leading to perturbation of physiology and behavior. Site(s) and mechanism(s) of ethanol–BK channel interaction are unknown. We demonstrate that ethanol docks onto a water-accessible site that is strategically positioned between the slo1 calcium-sensors and gate. Ethanol only accesses this site in presence of calcium, the BK channel’s physiological agonist. Within the site, ethanol hydrogen-bonds with K361. Moreover, substitutions that hamper hydrogen bond formation or prevent ethanol from accessing K361 abolish alcohol action without altering basal channel function. Alcohol interacting site dimensions are approximately 10.7 × 8.6 × 7.1 Å, accommodating effective (ethanol-heptanol) but not ineffective (octanol, nonanol) channel activators. This study presents: (i) to our knowledge, the first identification and characterization of an n-alkanol recognition site in a member of the voltage-gated TM6 channel superfamily; (ii) structural insights on ethanol allosteric interactions with ligand-gated ion channels; and (iii) a first step for designing agents that antagonize BK channel-mediated alcohol actions without perturbing basal channel function.Alcohol (ethyl alcohol, ethanol) is a psychoactive agent that has been overwhelmingly consumed by mankind across cultures and civilizations. Alcohol actions on central nervous system (CNS) physiology and behavior are largely independent of beverage type but due to ethanol itself (1). Ethanol alters cell excitability by modifying function of transmembrane (TM) ion channel proteins, including K+ channels. These channels constitute the most heterogeneous and extensive group of ion channels, its members belonging to TM2, TM4, and TM6 protein superfamilies. Within this myriad of proteins, several K+ channels have been shown to modify behavior in response to acute exposure to ethanol concentrations that reach the CNS and other excitable tissues during alcohol drinking (2–5). However, with the sole exception of the TM2, G protein-regulated inward rectifier K+ (GIRK) channel (6), there is no structural information on ethanol-K+ channel protein interacting sites currently available.Voltage/Ca2+-gated, large conductance K+ channels (BK), which are members of the TM6 voltage-gated ion channel superfamily, constitute major mediators of alcohol actions in excitable tissues. Acute exposure to ethanol levels reached in CNS during alcohol intoxication alters BK-mediated currents and thus, elicits widespread and profound modifications in physiology and behavior. In rodent models, acute ethanol exposure leads to reduced vasopressin, oxytocin and growth hormone release with consequent perturbation in physiology and behavior (7), altered firing rates in nucleus accumbens (8) and dorsal root ganglia neurons (9), and alcohol-induced cerebral artery constriction (10, 11). Moreover, studies in both mammals and invertebrate models demonstrate that ethanol targeting of neuronal BK is involved in development of alcohol tolerance and dependence (12–16). Although the physiological and behavioral consequences of ethanol disruption of BK function have been well documented, it remains unknown whether alcohol modification of BK function results from drug interaction with a defined recognition site(s) in a protein target vs. physical perturbation of the proteolipid environment where the BK protein resides. Thus, location and structural characteristics of the ethanol-recognition site(s), as well as nature of chemical bonds between ethanol and functional target that lead to modification of BK function, remain unknown.Ethanol-induced regulation of BK channels is fine-tuned by many factors, including the BK channel-forming slo1 protein (α subunit) isoform (17) and its modification by phosphorylation (18), BK channel accessory (β) subunits (11), the channel-activating ionic ligand (19) and the lipid microenvironment around the BK protein complex (20). However, ethanol perturbation of BK function is sustained when the slo1 protein is probed with the alcohol in cell-free membrane patches (19–21) or after protein reconstitution into artificial lipid bilayers (22). We recently demonstrated that perturbation of slo1 function by ethanol concentrations reached in blood during alcohol intoxication does not extend to Na+-gated slo2 and pH-gated slo3 channels, which are phylogenetically and structurally related to slo1. However, ethanol sensitivity does extend to a prokaryotic K+ channel from Methanobacterium thermoautotrophicum (MthK) (23), a TM2 ion channel that shares basic -driven gating mechanisms with slo1 (24). Collectively, these studies lead us to hypothesize that ethanol-recognition site(s) involved in alcohol modification of BK current exists in the slo1 cytosolic -sensing tail domain (CTD).Based on crystallographic data of the slo1 CTD and primary alignment of slo1-related ion channels that share ethanol sensitivity, we first identified eight putative ethanol recognition regions in the slo1 CTD. Using computational modeling, point amino acid substitutions and electrophysiology, we identified a distinct pocket as the ethanol-recognition site that leads to alcohol modification of BK current. This site has a few common characteristics of alcohol-binding protein sequences (25), yet presents features that differ from those of the alcohol site described in GIRK (6). In opposition to GIRK currents, which can be potentiated by alcohol in absence of G proteins (6), ethanol modulation of BK currents is dependent on the presence of (19). Our data strongly suggest that ethanol access to the newly identified BK ethanol-recognition site depends on the levels associated with the slo1 CTD. Thus, current data not only provide a structural basis for understanding –alcohol allosterism on BK channels but could render structural insights on other ligand-gated channels that are activated by ethanol in presence of their natural ligand (26–30). Finally, present data document that the newly identified site plays a critical role in BK channel sensitivity to long-chain alkanols and explain the reported chain length differential sensitivity (“cutoff”) of linear n-alkanols to modify BK current (31).Identification of a distinct alcohol-sensing site in BK channels opens the door for rational design of pharmaceuticals to counteract widespread effects of alcohol intoxication in the body without altering basal BK channel function. Because this site is present in human BK protein (), it is possible that genetic, epigenetic or other modifications of the alcohol-sensing site in BK channels could contribute to differential sensitivity to alcohol intoxication in humans. In addition, considering that individuals with low alcohol sensitivity are prone to developing heavy drinking ( AAA92290.132), an altered profile of alcohol-sensing site on BK channels might be included as a potential predictor, along with other targets, for developing alcohol preference. 相似文献
68.
James M. Hoffman Cyrine E. Haidar Mark R. Wilkinson Kristine R. Crews Donald K. Baker Nancy M. Kornegay Wenjian Yang Ching-Hon Pui Ulrike M. Reiss Aditya H. Gaur Scott C. Howard William E. Evans Ulrich Broeckel Mary V. Relling 《American journal of medical genetics. Part C, Seminars in medical genetics》2014,166(1):45-55
69.
G. V. K. Mohan Reddy C. H. Vamsi Krishna S. Lakshmi Venkat Aditya N. Chandra Sekhar Y. Mahadev Shastry 《Journal of Indian Prosthodontic Society》2014,14(2):172-178
Bone density is a key parameter in determining the surgical procedure of implant placement and for the predictability of successful implant treatment. Several clinical studies have shown lower survival rates of implants in maxilla which was attributed to poor bone quality. The present study compared the variations in the pre-operative and post-operative bone density values in Hounsfield units using CT between drilling technique and bone expansion technique at 0.25 and 1.0 mm sections at two sites which were selected in maxillary arch between the second premolar regions of either quadrants and results have shown bone expansion technique is superior to drilling technique in division III bone. 相似文献
70.