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1.
2.
Jyoti V. Chauthaiwale Takayuki Sakai Samuel E. Taylor Indu S. Ambudkar 《Pflügers Archiv : European journal of physiology》1996,432(1):105-111
The molecular mechanism(s) involved in mediating Ca2+ entry into rat parotid acinar and other non-excitable cells is not known. In this study we have examined the kinetics of
Ca2+ entry in fura-2-loaded parotid acinar cells, which were treated with thapsigargin to deplete internal Ca2+ pools (Ca2+-pool-depleted cells). The rate of Ca2+ entry was determined by measuring the initial increase in free cytosolic [Ca2+] ([Ca2+]i) in Ca2+-pool-depleted, and control (untreated), cells upon addition of various [Ca2+] to the medium. In untreated cells, a low-affinity component was detected with K
Ca = 3.4 ± 0.7 mM (where K
Ca denotes affinity for Ca2+) and V
max = 9.8 ± 0.4 nM [Ca2+]i /s. In thapsigargin-treated cells, two Ca2+ influx components were detected with K
Ca values of 152 ± 79 μM (V
max = 5.1 ± 1.9 nM [Ca2+]i/s) and 2.4 ± 0.9 mM (V
max = 37.6 ± 13.6 nM [Ca2+]i/s), respectively. We have also examined the effect of Ca2+ and depolarization on these two putative Ca2+ influx components. When cells were treated with thapsigargin in a Ca2+-free medium, Ca2+ influx was higher than into cells treated in a Ca2+-containing medium and, while there was a 46% increase in the V
max of the low-affinity component (no change in K
Ca), the high-affinity component was not clearly detected. In depolarized Ca2+-pool-depleted cells (with 50 mM KCl in the medium) the high-affinity component was considerably decreased while there was
an apparent increase in the K
Ca of the low-affinity component, without any change in the V
max. These results demonstrate that Ca2+ influx into parotid acinar cells (1) is increased (four- to five-fold) upon internal Ca2+ pool depletion, and (2) is mediated via at least two components, with low and high affinities for Ca2+.
Received: 30 October 1995/Received after revisionand accepted: 13 December 1995 相似文献
3.
Thomas J Cook Shanya Edwards Charlene Gyemah Manoj Shah Indu Shah Tiziana Fox 《Journal of the American Pharmacists Association》2004,44(5):583-586
OBJECTIVE: To determine the weight variation and calculated dosing variability of tablet fragments upon splitting unscored cyclobenzaprine hydrochloride 10 mg tablets using two common tablet splitting devices. DESIGN: Comparative pharmaceutics study. SETTING: Pharmacy school laboratory. PARTICIPANTS: Not applicable. INTERVENTIONS: Unscored cyclobenzaprine hydrochloride 10 mg tablets from one generic manufacturer were split with a tablet splitter or a kitchen knife by a licensed pharmacist and two doctor of pharmacy students (n = 15 tablets for each method per participant). MAIN OUTCOME MEASURES: Fragment weights (FWs) were compared with the theoretical weights (TWs), which were calculated as one half of the mean weight of the tablets used in each part of the experiment; means, relative standard deviations (RSDs), and percentages of TW were also calculated. RESULTS: The mean weight before splitting the 45 tablets with the tablet splitter was 136.6 +/- 2.1 mg (TW = 68.3 mg). The mean FW after splitting was 67.9 +/- 7.9 mg. The RSD of 11.6% corresponded to a range of 69.4% to 130.2% of the TW and an estimated drug content of the split fragments between 3.47 mg and 6.51 mg. The mean weight before splitting the 45 tablets cut with a kitchen knife was 136.6 +/- 2.0 mg (TW = 68.3 mg). The mean FW was 68.0 +/- 15.7 mg with a RSD of 23.2%, corresponding to a range of 49.9% to 149.5% of the TW and an estimated drug content of the split fragments between 2.49 mg and 7.48 CONCLUSION: Tablet fragments obtained after splitting this generic cyclobenzaprine 10 mg product varied considerably in weight and estimated drug content. Accordingly, splitting cyclobenzaprine 10 mg tablets to achieve 5 mg doses could result in unpredictable dosing and therapeutic response. 相似文献
4.
5.
Mohamed I. Husseiny Jeffrey Rawson Alexander Kaye Indu Nair Ivan Todorov Michael Hensel Fouad Kandeel Kevin Ferreri 《Vaccine》2014
Type 1 diabetes (T1D) is a metabolic disease that is initiated by the autoimmune destruction of pancreatic insulin-producing beta cells that is accompanied by the development of antigen-specific antibodies and cytotoxic T lymphocytes (CTLs). Several studies have shown that vaccination with diabetic autoantigens provides some protection against this process. In this report we describe a new oral vaccine that utilizes live attenuated Salmonella for simultaneous delivery of autoantigens in conjunction with immunomodulatory cytokine genes to immune cells in the gut mucosa. Recent data showed that live attenuated Salmonella is a safe, simple and effective vector for expression of antigens and cytokines by antigen-presenting cells (APCs) of gut-associated lymphatic tissue (GALT). This novel strategy was tested by fusion of the diabetic autoantigen preproinsulin with Salmonella secretory effector protein (SseF) of pathogenicity island-2 (SPI2). In this way the autoantigen is only expressed inside the host immune cells and translocated to the host cell cytosol. In addition Salmonella was used to deliver the gene for the immunomodulatory cytokine transforming growth factor beta (TGFβ) for host cell expression. Oral co-vaccination of 8 week-old non-obese diabetic (NOD) mice with three weekly doses of both the autoantigen and cytokine significantly reduced the development of diabetes, improved the response to glucose challenge, preserved beta cell mass, and reduced the severity of insulitis compared with controls and autoantigen alone. Combination therapy also resulted in increased circulating levels of IL10 four weeks post-vaccination and IL2 for 12 weeks post-vaccination, but without effect on proinflammatory cytokines IL6, IL12(p70), IL17 and IFNγ. However, in non-responders there was a significant rise in IL12 compared with responders. Future studies will examine the mechanism of this vaccination strategy in more detail. In conclusion, Salmonella-based oral vaccines expressing autoantigens combined with imunomodulatory cytokines appears to be a promising therapy for prevention of T1D. 相似文献
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8.
Vikram Kumar Yeragani Arindam Barua Indu Sattiraju Nikhil Mallavarapu 《Cardiovascular Engineering》2003,3(4):141-146
In this study, we evaluated the effectiveness of the statistic, Weighted Coherence in relation to the average or mean coherence in a particular frequency band after cross-spectral analysis. In time domain, correlation coefficient explains the relationship between two variables of interest, and a similar statistic in frequency domain using cross-spectral analysis is referred to as coherence, which is equivalent to the squared correlation coefficient and ranges from zero to unity. In this study, we show that weighted coherence is much more sensitive to various challenges within the same subject and also may be a more sensitive indicator of group differences in different frequency bands. Our data on normal subjects and patients with panic disorder during supine and standing postures during normal breathing, and also at different breathing rates throw new light on the sensitivity of this previously described novel index to quantify coherence between two related time series such as beat-to-beat heart rate and QT interval. 相似文献
9.
10.
Wee Chee Tan Indu Bala Jaganath Rishya Manikam Shamala Devi Sekaran 《International journal of medical sciences》2013,10(13):1817-1829
Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug. 相似文献