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101.
Anand BS Patel J Mitra AK 《The Journal of pharmacology and experimental therapeutics》2003,304(2):781-791
The oligopeptide transporter may be exploited to enhance the absorption of drugs by synthesizing their dipeptide ester prodrugs, which may be recognized as its substrates. Various dipeptide esters of acyclovir (ACV), an antiviral nucleoside analog, were synthesized. Enzymatic hydrolysis and affinity of the prodrugs toward the human intestinal peptide transporter hPEPT1 were studied using the human intestinal Caco-2 cell line. Affinity studies were performed by inhibiting the uptake of [(3)H]glycylsarcosine by the prodrugs. The uptake of glycylsarcosine was found to be saturable at higher concentrations and was competitively inhibited by the prodrugs of ACV. All prodrugs except Tyr-Gly-ACV demonstrated a higher affinity (1.41-4.96 mM) toward hPEPT1 than cephalexin (8.19 +/- 2.12 mM), which was used as a positive control. Two prodrugs, Gly-Val-ACV and Val-Val-ACV, showed comparable affinity to Val-ACV, an amino acid prodrug of ACV recognized by PEPT1/PEPT2. The permeability of Gly-Val-ACV (2.99 +/- 0.59 x 10(-6) cm/s) across Caco-2 was comparable with that of Val-ACV (3.01 +/- 0.21 x 10(-6) cm/s) and was significantly inhibited (63%) in presence of glycylsarcosine. The transport of GVACV across Caco-2 was saturable at higher concentrations, and the parameters were calculated as K(m) 3.16 +/- 0.31 mM and V(max) 0.014 +/- 0.00058 nmol cm(-2) min(-1). Overall, the results suggest that the dipeptide prodrugs of ACV have a high affinity toward the intestinal oligopeptide transporter hPEPT1 and therefore seem to be promising candidates in the treatment of ocular and oral herpesvirus infections, because cornea and intestinal epithelia seem to express the oligopeptide transporters. 相似文献
102.
Clomiphene citrate (CC), as a medication in male infertility, improves the sperm parameters in oral consumption but various detrimental side effects have been reported including testicular tumours, gynaecomastia, skin allergic reactions and ocular symptoms. Therefore, this study was designed to evaluate the in vitro effects of CC on sperm parameters and fertilisation rate in IVF protocol. Sperm samples of NMRI adult mice were divided into six groups: group 1 received no treatment (control group), while groups of 2, 3, 4, 5 and 6 (experimental groups) were incubated with the doses of 0.001, 0.01, 0.1, 1 and 10 µg/ml of CC in culture medium respectively. Sperm parameters (viability, morphology and motility), DNA fragmentation levels and fertilisation rate in IVF were evaluated. The results demonstrated that the doses of 0.1 µg/ml (p = .000007 for viability and p = .00006 for fertilisation rate) and 1 µg/ml (p = .032 for viability and p = .005 for fertilisation rate) CC cause a significant improvements; also, the dose of 0.1 µg/ml CC found effective on sperm motility (p = .0003). In the field of IVF, the application of 0.1 and 1 µg/ml of CC in the culture medium may improve the sperm parameters in IVF protocol with no side effects. 相似文献
103.
Hadi Tabibi Atefeh As’habi Mitra Mahdavi-Mazdeh Mehdi Hedayati Behnaz Nozary-Heshmati 《International urology and nephrology》2014,46(10):2015-2020
Purpose
The present study was designed to compare novel risk factors for cardiovascular diseases (CVD) between hemodialysis (HD) patients with or without protein-energy wasting (PEW) for determining novel risk factors for CVD in HD patients with PEW.Methods
In this cross-sectional study, 291 HD patients were randomly selected from among 2,302 adult HD patients in Tehran hemodialysis centers. The presence of PEW in HD patients was determined by subjective global assessment. In addition, 4 mL blood was obtained before dialysis and analyzed for serum concentrations of novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)].Results
Serum CRP and sICAM-1 were significantly higher in HD patients with PEW as compared to those without PEW (P < 0.01), whereas there were no significant differences in serum sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a) between the two groups. Serum CRP and sICAM-1 were significantly higher in HD patients with PEW type IIa and IIb than in those with PEW type I (P < 0.01).Conclusion
The present study indicates that serum CRP and sICAM-1, as two CVD risk factors, increase in HD patients with PEW as compared to those without PEW and these increases occur in HD patients with PEW type IIa and IIb who have inflammation. 相似文献104.
Mohammad Javad Tarrahi Afarin Rahimi-Movaghar Hojjat Zeraati Masoumeh Amin-Esmaeili Abbas Motevalian Ahmad Hajebi Vandad Sharifi Reza Radgoodarzi Mitra Hefazi Akbar Fotouhi 《Addictive behaviors》2014
The aim of this study was to determine the agreement between the two systems in opioid users in the general population and a clinical sample. Two series of data were used in this study. The first was the data of 236 home-residing opioid abusers aged 15–64, who had previously participated in the Iran Mental Health Survey (IranMHS) in 2011, and the second was the data of 104 general psychiatry patients from inpatient or outpatient wards of two psychiatry hospitals in Tehran. Opioid use disorders were evaluated with CIDI-version 2.1. The disorders were assessed in all participants who used opioid substances for at least 5 times during the past 12 months. In the sample from the general population, the agreement between the two systems on the diagnosis of dependence was excellent (0.81). The agreement between the two systems on the diagnosis of abuse and harmful use was 0.41. In the clinical sample, the agreement between the two systems on the diagnosis of dependence or any opioid use disorder was 0.96 and 0.93, respectively. The agreement between abuse and harmful use was 0.9 and − 0.02 with and without regarding hierarchy, respectively. The inter-rater reliability of both DSM-IV and ICD-10 systems for all diagnosis was more than 0.95. The results of the diagnosis of dependence in the two systems had a weak concordance with treatment. The diagnostic criteria of DSM-IV and ICD-10 regarding dependence are very similar and the diagnosis produced by each system is concordant with the other system. However, the two systems have noticeable discrepancies in the diagnosis of abuse and harmful use. The discrepancies result from their conceptual differences and necessitate further revision in the definition of these disorders in the two systems. 相似文献
105.
Tina Penick Brock Mitra Assemi Robin L. Corelli Shareen Y. El-Ibiary Jan Kavookjian Beth A. Martin Karen Suchanek Hudmon 《American journal of pharmaceutical education》2014,78(5)
Objective. To assess the outcomes from an 11-year nontraditional professional development activity implemented by female faculty members at several colleges and schools of pharmacy.Design. Within the context of an online fantasy football league, faculty members practiced community-based faculty development strategies, including peer mentoring, skills development, constructive feedback and other supportive behaviors.Assessment. Data were extracted from curriculum vitae to characterize the academic progress of participants and to quantify scholarly work collaborations among league members. Analyses were limited to members who had participated in the league for 10 or more consecutive years. Seventy-one collaborative scholarly works occurred among team managers, including presentation of 20 posters and 2 oral presentations at national or international meetings, publication of 29 peer-reviewed articles and 15 book chapters, and funding of 5 research projects.Conclusion. Social media platforms can foster nontraditional faculty development and mentoring by enhancing connectivity between pharmacy educators who share similar interests. 相似文献
106.
Structure‐Based Design and Synthesis of a Small Molecule that Exhibits Anti‐inflammatory Activity by Inhibition of MyD88‐mediated Signaling to Bacterial Toxin Exposure
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Shahabuddin Alam Sacha Javor Melissa Degardin Dariush Ajami Mitra Rebek Teri L. Kissner David M. Waag Julius Rebek Jr Kamal U. Saikh 《Chemical biology & drug design》2015,86(2):200-209
Both Gram‐positive and Gram‐negative pathogens or pathogen‐derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88‐mediated pro‐inflammatory cellular immunity for host defense. However, dysregulated MyD88‐mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB‐loop structure of MyD88 was capable of inhibiting pro‐inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non‐polar cyclohexane linker which strongly inhibited the production of pro‐inflammatory cytokines in human primary cells to SEB (IC50 1–50 μm ) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10–200 μm ). Consistent with cytokine inhibition, in a ligand‐induced cell‐based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS‐induced MyD88‐mediated NF‐kB‐dependent expression of reporter activity (IC50 10–30 μm ). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro‐inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin‐induced inflated pro‐inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic. 相似文献
107.
Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography
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Llinás RR Ribary U Jeanmonod D Kronberg E Mitra PP 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(26):15222-15227
Spontaneous magnetoencephalographic activity was recorded in awake, healthy human controls and in patients suffering from neurogenic pain, tinnitus, Parkinson's disease, or depression. Compared with controls, patients showed increased low-frequency theta rhythmicity, in conjunction with a widespread and marked increase of coherence among high- and low-frequency oscillations. These data indicate the presence of a thalamocortical dysrhythmia, which we propose is responsible for all the above mentioned conditions. This coherent theta activity, the result of a resonant interaction between thalamus and cortex, is due to the generation of low-threshold calcium spike bursts by thalamic cells. The presence of these bursts is directly related to thalamic cell hyperpolarization, brought about by either excess inhibition or disfacilitation. The emergence of positive clinical symptoms is viewed as resulting from ectopic gamma-band activation, which we refer to as the "edge effect." This effect is observable as increased coherence between low- and high-frequency oscillations, probably resulting from inhibitory asymmetry between high- and low-frequency thalamocortical modules at the cortical level. 相似文献
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