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991.
Because each cancer is a heterogeneous mix of cancer cells at different stages of development, we are faced with trying to treat many different diseased cells all at once. An authentic approach is to build a genomic and proteomic profile of a patient, identify the target oncogenes, and prescribe the combination of targeted drugs tailored for that patient. However, there are many practical problems with this personalized medicine approach: (i) cancers often generate treatment-resistant phenotypes, (ii) the treatment could be enormously expensive, and (iii) most of the targeted drugs have not been developed yet. We propose a different approach: therapies that combine 2-deoxyglucose (2DG) with Bcl-2 antagonist such as ABT-263/737 (ABT). Proapoptotic protein Bak is normally sequestered by Mcl-1 and Bcl-xL. Only when Bak is released from both Mcl-1 and Bcl-xL can it induce apoptosis. 2DG can prime highly glycolytic cells by dissociating Bak-Mcl-1 complex. Some brain cells and most cancer cells are primed by 2DG. ABT can bind to Bcl-xL, dissociating Bak-Bcl-xL complex, freeing Bak and inducing apoptosis. Because ABT cannot cross blood-brain barrier, the only cells exposed to both agents are highly glycolytic cancer cells located outside the brain. Because ABT directly triggers apoptosis at the step very near the terminal point of apoptosis, 2DG-ABT combination therapies are applicable to many types of cancer at all stages of development, with little side effect. 相似文献
992.
Microsurgical free flap transfer in previously irradiated and operated necks: feasibility and safety
Kadota H Fukushima J Yoshida S Kamizono K Kumamoto Y Masuda M Nakashima T Yasumatsu R Komune S 《Auris, nasus, larynx》2012,39(5):496-501
Objectives
Microsurgery is difficult to perform in necks that have been previously irradiated and operated upon because of the limited availability of recipient vessels. The objective of this study was to clarify the feasibility and safety of performing microsurgery in necks that are scarred and fibrous owing to previous treatment.Methods
Twenty patients whose necks were previously irradiated and operated upon and who underwent free tissue transfer were included in this study. All patients had been previously administered an average of 60.7 (range, 30–95) Gy of radiotherapy. Thirteen patients had undergone hemilateral neck dissections, 5 patients had undergone bilateral neck dissections, 8 patients had undergone (pharyngo)laryngectomies, and 10 patients had undergone prior flap transfer. The success rate of microsurgery and the selection of recipient vessels were examined.Results
All recipient vessels could be adopted in the neck field without vessel grafting. One patient developed necrosis of the flap, which was salvaged with retransfer of another flap after trimming the same cervical vessels. For the remaining 19 patients, free tissue transfers were successful.Conclusions
Suitable recipient vessels are residual and available even in the previously irradiated and operated neck field. When performed properly, free tissue transfer in the previously treated neck is not as risky a surgery as was generally believed. 相似文献993.
Yamakawa Y Ohtsuka Y Ohtani K Fujii T Nagata S Yamashiro Y Shimizu T 《Drugs in R&D》2010,10(3):147-154
Background: Although the efficacy of leukotriene receptor antagonists (LTRAs) for bronchial asthma is already established, their effect on food allergy remains unclear.Objective: To investigate the efficacy of LTRAs in children with food allergy. Methods: This retrospective study examined 65 children with food allergy who were aged between 3 and 36 months (mean 14±9.6 months) from 2005 to 2008. Thirty-two children were treated as a dietary control group by avoiding any antigenic foods to which they had previously experienced adverse reactions. The remaining 33 children, designated the LTRA group, were treated with pranlukast (7mg/kg bodyweight/day) in addition to maintaining dietary control. Clinical symptoms and laboratory data before and after 1 year of treatment were compared between the groups.Results: Allergic symptoms improved in both the dietary controlled and LTRA groups, and there was no significant difference observed in the clinical parameters examined between the groups after the 1-year trial. Peripheral eosin-ophil count, serum IgE, interleukin (IL)-4, IL-5, IL-6, and eosinophil cationic protein (ECP) levels in children with food allergy were above standardized values in both groups. Although both the dietary controlled and LTRA groups showed a decreased eosinophil count (−273 ± 232 vs -595 ± 295/μL; p < 0.05 and p < 0.001, respectively), only children treated with LTRA showed a significant decrease in serum IgE (-73.5 ± 115 IU/mL; p < 0.01); conversely, the control group exhibited a significant increase in serum IgE (+159 ± 138 IU/mL; p < 0.01). Furthermore, the LTRA group also showed a significant decrease in serum IL-4 (54.5 ± 31.0 to 27.3 ± 10.1 pg/mL), IL-5 (6.7 ± 5.2 to 5.0 ± 0.4 pg/mL), and ECP (45.4 ± 15.0 to 15.0 ± 9.8 μg/L) levels (p < 0.05 for each).Conclusion: Early intervention with LTRAs may be effective in regulating eosinophil count and serum IgE, IL-4, IL-5, and ECP levels. These data support the potential effectiveness of LTRAs in young children with food allergy to prevent further allergic development. 相似文献
994.
There is growing body of evidence that nitric oxide (NO)-cGMP-PKG signaling plays a central role in negative regulation of cardiovascular (CV) responses and its disorders through suppressed Ca(2+) dynamics. Other lines of evidence also reveal the stimulatory effects of this signaling on some CV functions. Recently, transient receptor potential (TRP) channels have received much attention as non-voltage-gated Ca(2+) channels involved in CV physiology and pathophysiology. Available information suggests that these channels undergo both inhibition and activation by NO via PKG-mediated phosphorylation and S-nitrosylation, respectively, and also act as upstream regulators to promote endothelial NO production. This review summarizes the roles of NO-cGMP-PKG signaling pathway, particularly in regulating TRP channel functions with their associated physiology and pathophysiology. 相似文献
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Myoung Kwon Choi ZhiChao Wang Tatsuma Ban Hideyuki Yanai Yan Lu Ryuji Koshiba Yukana Nakaima Sho Hangai David Savitsky Makoto Nakasato Hideo Negishi Osamu Takeuchi Kenya Honda Shizuo Akira Tomohiko Tamura Tadatsugu Taniguchi 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(42):17870-17875
999.
Both neurologists and urologists might encounter patients with acute urinary retention due to benign inflammatory nervous
diseases. Based on the mechanism of urinary retention, these disorders can be divided into two subgroups: disorders of the
peripheral nervous system (e.g., sacral herpes) or the central nervous system (e.g., meningitis-retention syndrome [MRS]).
Laboratory abnormalities include increased herpes virus titers in sacral herpes, and increased myelin basic protein in the
cerebrospinal fluid (CSF) in some cases with MRS. Urodynamic abnormality in both conditions is detrusor areflexia; the putative
mechanism of it is direct involvement of the pelvic nerves in sacral herpes; and acute spinal shock in MRS. There are few
cases with CSF abnormality alone. Although these cases have a benign course, management of the acute urinary retention is
necessary to avoid bladder injury due to overdistension. Clinical features of sacral herpes or MRS differ markedly from those
of the original “Elsberg syndrome” cases.
Received in revised form 22 October 2005 相似文献
1000.
Ryuji Sakakibara MD PhD Tomoyuki Uchiyama MD PhD Tomonori Yamanishi MD Masahiko Kishi 《Movement disorders》2010,25(1):2-12
Bladder dysfunction (urinary urgency/frequency) and sexual dysfunction (erectile dysfunction) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, genitourinary autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine‐basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine‐oxytocin pathways, which normally promote libido and erection. The pathophysiology of the genitourinary dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. © 2010 Movement Disorder Society 相似文献