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排序方式: 共有184条查询结果,搜索用时 375 毫秒
71.
Varamini P Mansfeld FM Blanchfield JT Wyse BD Smith MT Toth I 《Journal of medicinal chemistry》2012,55(12):5859-5867
The endogenous opioid peptide endomorphin-1 (1) was modified by attachment of lactose to the N-terminus via a succinamic acid spacer to produce compound 2. The carbohydrate modification significantly improved the metabolic stability and membrane permeability of 2 while retaining μ-opioid receptor binding affinity and agonist activity. Analogue 2 produced dose-dependent antinociceptive activity following intravenous administration in a chronic constriction injury (CCI) rat model of neuropathic pain with an ED(50) of 8.3 (± 0.8) μmol/kg. The corresponding ED(50) for morphine was 2.6 (± 1.4) μmol/kg. Importantly, compound 2 produced dose-dependent pain relief after oral administration in CCI rats (ED(50) = 19.6 (± 1.2) μmol/kg), which was comparable with that of morphine (ED(50) = 20.7 (±3.6) μmol/kg). Antineuropathic effects of analogue 2 were significantly attenuated by pretreatment of animals with the opioid antagonist naloxone, confirming opioid receptor-mediated analgesia. In contrast to morphine, no significant constipation was produced by compound 2 after oral administration. 相似文献
72.
Pramil N. Singh Michael Batech Pegah Faed Karen Jaceldo-Siegl Marcia Martins Gary E. Fraser 《Nutrition and cancer》2013,65(8):1315-1321
We studied Adventist Health Study 2 (AHS-2) cohort members to determine the reliability of long-term recall of adult dietary intake that occurred 33 years ago. Establishing the reliability of these measures supports studies of how dietary exposure across the life course affects risk of cancer and other noncommunicable disease outcomes. Among 1816 AHS-2 cohort members, we conducted a statistical comparison of long-term recall of meat, fish, dairy, and eggs at AHS-2 baseline with their report of current diet 33 years before AHS-2 baseline at an age of 30–60 years. Major findings are as follows: 1) a high correlation for frequency of red meat (R = 0.71), poultry (R = 0.67), and fish (R = 0.60); lower correlations for dairy (R = 0.19) and eggs (R = 0.28); 2) good concordance for dichotomous measures of red meat [sensitivity: 0.70; specificity: 0.92; positive predictive value (PPV): 0.91], poultry (sensitivity: 0.76; specificity: 0.87; PPV: 0.83), fish (sensitivity: 0.61; specificity: 0.93; PPV: 0.89), dairy (sensitivity: 0.95; specificity: 0.57; PPV: 0.99), and eggs (sensitivity: 0.95; specificity: 0.41; PPV: 0.96); negative predictive value for dairy and eggs was poor. Among older AHS-2 cohort members, we found good reliability of recall of red meat, poultry, and fish intake that occurred 33 years earlier. 相似文献
73.
Pegah Pouladian Toyohiko Yamauchi Nicole M. Wakida Veronica Gomez-Godinez Michael W. Berns Daryl Preece 《Biomedical optics express》2021,12(7):4020
In this paper, we propose a new system for studying cellular injury. The system is a biophotonic work station that can generate Laser-Induced Shockwave (LIS) in the cell culture medium combined with a Quantitative Phase Microscope (QPM), enabling the real-time measurement of intracellular dynamics and quantitative changes in cellular thickness during the damage and recovery processes. In addition, the system is capable of Phase Contrast (PhC) and Differential Interference Contrast (DIC) microscopy. Our studies showed that QPM allows us to discern changes that otherwise would be unnoticeable or difficult to detect using phase or DIC imaging. As one application, this system enables the study of traumatic brain injury in vitro. Astrocytes are the most numerous cells in the central nervous system (CNS) and have been shown to play a role in the repair of damaged neuronal tissue. In this study, we use LIS to create a precise mechanical force in the culture medium at a controlled distance from astrocytes and measure the quantitative changes, in order of nanometers, in cell thickness. Experiments were performed in different cell culture media in order to evaluate the reproducibility of the experimental method. 相似文献
74.
Ghorbanihaghjo A Veisi P Argani H Aghaeishahsavari M Noroozianavval M Rashtchizadeh N Mesgari M Safa J Babaei H 《Clinical and experimental nephrology》2008,12(1):65-73
Background In this study the effect of losartan and enalapril on the reduction of DNA damage was evaluated in regard to renin-angiotensin
system (RAS) polymorphisms.
Methods After determination of genotypes of RAS polymorphism by PCR, 64 renal transplant recipients were randomly allocated to one
of four groups: the first and second groups were treated with E (E+: 10 mg/day) and L (L+: 50 mg/day) alone, respectively. The third group received E+L (E+L+: 10 + 50 mg/day), and the forth group received no medication (E−L−). The subjects were followed for 8 weeks. After a 2-week washout period, the E group changed to L and vice versa as a cross-over
design. They were followed for another 8 weeks. Before and after treatment, we checked 8-OHdG and malondialdehyde (MDA) as
biomarkers of DNA damage and lipid peroxidation, respectively.
Results 8-OHdG levels were significantly decreased after treatment in the E+L+ and L+ groups (P < 0.001, P = 0.001, respectively). Only the TT genotype of AGT had the most antioxidative role regarding the treatment (P = 0.01). We found a remarkable correlation between MDA and DNA damage levels before and after intervention (r = 0.48, P < 0.001; r = 0.35, P = 0.006).
Conclusion The protective effects of L+ and E+L+ on DNA breaks are surprising regarding the RAS polymorphisms. 相似文献
75.
Seyed‐Moayed Alavian Seyed Vahid Tabatabaei Maryam Keshvari Bita Behnava Seyyed Mohammad Miri Pegah Karimi Elizee Kamran Bagheri Lankarani 《Liver international》2010,30(8):1173-1180
Background/aims: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti‐HCV thrapy but there is little information about safety and efficacy of peginterferon α‐2a and ribavirin combination therapy in these patients. Material and methods: In an open‐label single‐treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 μg of Pegasys® and 800–1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). Results: Two hundred and twenty‐five subjects [61%, 95% confidence interval (CI) 56–66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1–3.1), genotype non‐1 OR=1.8 (95% CI 1.1–3.2), BMI<25 OR=2.1 (95% CI 1.3–3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1–3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow‐up after treatment cessation. Conclusions: Peginterferon alpha‐2a in combination with weight‐based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non‐1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non‐1 are the major determinants of SVR achievement in these patients. 相似文献
76.
Seyed Mohammad Masoud Shoushtarian Mohammad Sadegh Mirdehghan Farashah Pegah Valiollahi Ali Tajik Farhad Adhamimoghaddam Shervin Malekzadeh 《Indian journal of pediatrics》2010,77(5):577-578
Amblyopia is a common visual impairment in developing countries and a major but neglected health issue. Definite diagnosis
in children is difficult due to lower cooperation in this age range. Electroretinography (ERG) may be a useful objective method
for diagnosis of amblyopia. In this study, we compare the ERG findings in amblyopic and non-amblyopic children. It is concluded
that ERG is a sensitive and objective diagnostic test for amblyopia. It is recommended that ERG be used as a quick tool for
diagnosis of amblyopia in children. 相似文献
77.
The enzymatic stability, antitumor activity, and gonadotropin stimulatory effects of glycosylated luteinizing hormone-releasing hormone (LHRH) analogs were investigated in this study. Conjugation of carbohydrate units, including lactose (Lac), glucose (GS), and galactose (Gal) to LHRH peptide protected the peptide from proteolytic degradation and increased the peptides’ half-lives in human plasma, rat kidney membrane enzymes, and liver homogenate markedly. Among all seven modified analogs, compound 1 (Lac-[Q1][w6]LHRH) and compound 6 (GS4-[w6]LHRH) were stable in human plasma during 4 h of experiment. The half-lives of compounds 1 and 6 improved significantly in kidney membrane enzymes (from 3 min for LHRH to 68 and 103 min, respectively). The major cleavage sites for most of the glycosylated compounds were found to be at Trp3-Ser4 and Ser4-Tyr5 in compounds 1–5. Compound 6 was hydrolyzed at Ser4-Tyr5 and the sugar conjugation site. The antiproliferative activity of the glycopeptides was evaluated on LHRH receptor-positive prostate cancer cells. The glycosylated LHRH derivatives had a significant growth inhibitory effect on the LNCaP cells after a 48-h treatment. It was demonstrated that compound 1 significantly increased the release of luteinizing hormone (LH) at 5 and 10 nM concentrations and compound 5 (GS-[Q1]LHRH) stimulated the release of follicle-stimulating hormone (FSH) at 5 nM concentration in dispersed rat pituitary cells (p < 0.05). In our studies, compound 1-bearing lactose and d-Trp was the most stable and active and is a promising candidate for future preclinical investigations in terms of in vitro biological activity and metabolic stability.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-015-9769-x) contains supplementary material, which is available to authorized users.KEY WORDS: antiproliferative activity, carbohydrate conjugation, LH and FSH release, LHRH, peptide 相似文献78.
Yousef Fazel Brian Lam Pegah Golabi Zobair Younossi 《Expert opinion on drug safety》2015,14(8):1317-1326
Introduction: The approval of sofosbuvir (SOF), a nucleotide analogue NS5B polymerase inhibitor, and ledipasvir (LDV), a NS5A inhibitor, marked a new chapter in IFN and ribavirin-free treatment of hepatitis C virus (HCV). This drug reduces adverse events associated with IFN therapy.Areas Covered: The purpose of this paper is to evaluate the safety and efficacy of LDV/SOF. Clinical trials illustrating safety and efficacy of LDV/SOF are reviewed and compared to other IFN and ribavirin-free treatment options available.Expert Opinion: In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug–drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug–drug interactions. 相似文献
79.
Hamade Nour Bhavsar-Burke Indira Jansson-Knodell Claire Wani Sachin Patel Swati G. Ehrlich Adam C. Paine Elizabeth Hosseini-Carroll Pegah Menard-Katcher Paul Fayad Nabil 《Digestive diseases and sciences》2022,67(6):2019-2028
Digestive Diseases and Sciences - Amid the COVID-19 pandemic, medical education organizations endorsed a virtual recruitment format, representing a stark change from traditional in-person... 相似文献
80.