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1.
World J Psychiatry ; 13(6): 331-339, 2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37383283

ABSTRACT

There are various types of traumatic stimuli, such as catastrophic events like wars, natural calamities like earthquakes, and personal trauma from physical and psychological neglect or abuse and sexual abuse. Traumatic events can be divided into type I and type II trauma, and their impacts on individuals depend not only on the severity and duration of the traumas but also on individuals' self-evaluation of the traumatic events. Individual stress reactions to trauma include posttraumatic stress disorder (PTSD), complex PTSD and trauma-related depression. Trauma-related depression is a reactive depression with unclear pathology, and depression occurring due to trauma in the childhood has gained increasing attention, because it has persisted for a long time and does not respond to conventional antidepressants but shows good or partial response to psychotherapy, which is similar to the pattern observed for PTSD. Because trauma-related depression is associated with high risk of suicide and is chronic with a propensity to relapse, it is necessary to explore its pathogenesis and therapeutic strategy.

2.
BMC Psychiatry ; 23(1): 277, 2023 04 20.
Article in English | MEDLINE | ID: mdl-37081401

ABSTRACT

AIM: To analyze the changes of chronotypes in patients with depression before and after treatment, and explore the effects of different chronotypes on antidepressant treatment and the dimensions of common symptoms in patients with depression. METHODS: 180 patients with depression were selected from 10 tertiary psychiatric hospitals in Zhejiang province, according to the scores of morningness-eveningness questionnaire (MEQ), the patients were divided into three groups: early-type group, middle-type group and late-type group. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale anxiety Scale (HAMA), Snaith Hamilton Pleasure Scale (SHAPS), multidimensional fatigue inventory-20(MFI-20) and Pittsburgh sleep quality index (PSQI) were measured at baseline and at the end of the 2nd, 4th, 8th and 12th weeks, the variance analysis of repeated measures was used to analyze the change of each index in the study. The remission rate of depression at each time point was statistically analyzed. RESULTS: Of the 180 patients included in the study, 26 were lost to follow-up, and 154 were finally included in the analysis. At baseline, 14.93%, 56.5% and 28.57% of the subjects were diagnosed as middle-late type, middle-late type and early-late type respectively, the total scores of Shaps and MFI-20 in the early-type group were higher than those in the late-type group and the middle-type group (p < 0.05). During the 12-week antidepressant treatment period, the time effect of PSQI, Shaps, MFI-20 and MEQ had interaction with different time groups (p < 0.05). During the treatment, the multiple symptom dimensions of depression were improved to different degrees, but the changing trend was not the same, and the recovery of the anhedonia was obviously delayed, in early-type patients, there are many symptoms such as loss of pleasure and sleep disorders. There was no significant effect on the remission rate of depression in different time type (p > 0.05) . CONCLUSION: The disorder of chronotypes is common in patients with depression. The time effect of different time type on different symptom dimension of depression was affected, but the effect on remission rate of depression was not significant. To strengthen the management of biological chronotype rhythm in patients with depression may be of great significance in the treatment of depression.


Subject(s)
Chronotype , Depressive Disorder, Major , Humans , Depressive Disorder, Major/psychology , Antidepressive Agents/therapeutic use , Patients , Surveys and Questionnaires
3.
Adv Biol (Weinh) ; 7(7): e2200317, 2023 07.
Article in English | MEDLINE | ID: mdl-36949542

ABSTRACT

Poly (acrylic) acid coated Mn3O4 nanoparticles (PAA@Mn3 O4 nanoparticles (PMO, 11.02 nm, -28.93 mV)) are synthesized to investigate whether they can help to improve maize drought tolerance and the relevant mechanisms behind this. In planta experimental results show that under drought (15% PEG 6000, polyethylene glycol, mimicking drought stress, 96 h), compared with the control plants, 500 mg L-1 PMO (root application, 96 h) improves maize drought tolerance, showing an increase of root length (21.6%), shoot length (21.2%), fresh weight (7.8%) and total protein (67.2%) content. In addition, PMO significantly decreases the malondialdehyde (MDA) content by 74.7% in maize under drought, compared with the control group. Further, PMO treated maize root apex shows significantly increased mitotic index (MI, 35.5%), and decreased hydrogen peroxide (40.9%). Compared with the control under drought (15% PEG, 96 h), thr root apex of maize plants treated with PMO (500 mg L-1 , root application, 96 h) have significantly lower level of H2 O2 . Overall, the results show that PMO can alleviate drought-inhibited cell mitosis activities via maintaining ROS (reactive oxygen species) homeostasis. In this study, it is not only shown that PMO can be a good nano-regulator candidate to improve maize drought tolerance, but also that PMO has potential to modulate plant cell mitosis activities.


Subject(s)
Drought Resistance , Manganese Compounds , Metal Nanoparticles , Zea mays , Zea mays/physiology , Manganese Compounds/pharmacology , Oxides/pharmacology , Mitosis , Plant Roots , Reactive Oxygen Species/metabolism , Malondialdehyde , Hydrogen Peroxide , Homeostasis
5.
Clin Transl Sci ; 16(3): 447-458, 2023 03.
Article in English | MEDLINE | ID: mdl-36495036

ABSTRACT

CSPCHA115 is a highly selective and potent antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability of single and multiple ascending doses of CSPCHA115 in Chinese healthy subjects. Two phase I studies both adopted a randomized, double-blind, placebo-controlled, single-center, and ascending-dose design. In the single ascending dose (SAD) study, subjects were randomly allocated to receive a single dose of CSPCHA115 (25-1000 mg) or a placebo. In the multiple ascending dose (MAD) study, 100, 200, 400, or 600 mg of CSPCHA115 or placebo were given to subjects once daily for 7 days. PK parameters were estimated by noncompartmental analysis. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs), clinical laboratory tests, electrocardiograms, vital signs, and physical examinations throughout the study period. Forty-eight healthy subjects were enrolled in the SAD study, and 40 healthy subjects were in the MAD study. Following single and multiple administrations, CSPCHA115 was rapidly absorbed with a median time to maximum concentration of ~0.5-3.5 h; and the systemic exposure of CSPCHA115 generally increased dose-proportionally within the dose range studied. Steady-state was approximately achieved by day 5, and <1.5-fold accumulation was observed following multiple doses. Mean terminal half-life was ~8.16-16.43 h after a single dose. CSPCHA115 was well-tolerated in both studies, with a low overall incidence of TEAEs. The most common TEAE related to CSPCHA115 was hypertriglyceridemia. No significant safety concerns were identified in healthy subjects.


Subject(s)
Asian People , East Asian People , Humans , Healthy Volunteers , Area Under Curve , Double-Blind Method , Dose-Response Relationship, Drug
6.
BioDrugs ; 36(3): 393-409, 2022 May.
Article in English | MEDLINE | ID: mdl-35594017

ABSTRACT

BACKGROUND: Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products). OBJECTIVES: This study compared the biosimilarity in pharmacokinetics (PK), safety, and immunogenicity between HLX11 and reference pertuzumab (approved in the US, the EU, and CN) in healthy Chinese male participants after a single infusion and further characterized the PK profile of HLX11. METHODS: Eligible individuals were randomized 1:1:1:1 to receive a single dose of 420 mg HLX11, US-, EU-, or CN-pertuzumab via intravenous infusion over 60 min. The primary endpoints were maximum serum drug concentration (Cmax), area under the serum concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC0-t), and AUC from time 0 to infinity (AUC0-∞). PK bioequivalence was established if the 90% confidence intervals (CIs) of the geometric mean ratios of the primary endpoints were between 80.0 and 125.0%. Secondary endpoints included other PK parameters, safety, and immunogenicity. RESULTS: A total of 160 participants were enrolled and randomly assigned to each group (n = 40 per group). The 90% CIs of the geometric mean ratios of the primary endpoints were all within the prespecified equivalence margins (HLX11 vs. pertuzumab [US-, EU-, CN-approved products]: Cmax 97.03-115.06%, 91.39-109.80%, 94.53-110.65%; AUC0-t 87.65-99.68%, 87.07-100.79%, 86.29-101.09%; AUC0-∞ 87.66-99.90%, 87.54-101.05%, 89.23-103.20%). The incidence of adverse drug reactions was comparable across the four groups. The presence of anti-drug antibodies or neutralizing antibodies had no obvious effect on PK. CONCLUSION: The PK, safety, and immunogenicity of HLX11 were highly similar to those of reference pertuzumab (US-, EU-, CN-approved products). The established bioequivalence supports further clinical trials of HLX11 in cancer treatment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04411550) and Chinadrugtrials.org.cn (CTR20200618).


Subject(s)
Biosimilar Pharmaceuticals , Antibodies, Monoclonal, Humanized , Area Under Curve , Biosimilar Pharmaceuticals/pharmacokinetics , China , Double-Blind Method , European Union , Healthy Volunteers , Humans , Male , Therapeutic Equivalency , United States
7.
Article in Chinese | MEDLINE | ID: mdl-33794615

ABSTRACT

Objective:To learn the hearing level and analyze the effect factors of hearing loss of the ear with normal hearing in patients with single sided deafness, and provide references for the treatment of single sided deafness. Methods:A retrospective analysis of pure threshold average of 89 patients with single sided deafness, it was divided into six groups,0-6 month group (14 cases), >6-12 month group (17 cases), >12-18 month group (15 cases), >18-24 month group (26 cases), >24-30 Month group (10 cases), >30-36 months group (7 cases) in accordance with the different duration of deafness, and compare the pure threshold average of each group; In accordance with the different ages of onset of deafness, it was divided into four groups, 21-30 years old group(18 cases), >30-40 years old group (24 cases), >40-50 years old group (30 cases), >50-60 years old group (17 cases), and pure threshold average of matching age of normal hearing was compared. Spearman correlation was used to analyze whether gender, side, age of onset of deafness, etiology of deafness, duration of deafness, and pure threshold average hearing were correlated. Results:As the duration of deafness in the affected ear increased, the average pure threshold in patients with single sided deafness increased. As the age of onset of deafness increased, there was a statistically significant difference in age-matched normal hearing. Age of onset of deafness and duration of deafness were the main factors affecting the pure threshold average. Conclusion:In clinical work, the degree of attention to patients with single sided deafness should be increased, hearing of the better hearing ear patients should be protected, and the quality of life will be improved.


Subject(s)
Deafness , Quality of Life , Adult , Hearing , Hearing Tests , Humans , Middle Aged , Retrospective Studies , Young Adult
8.
Biomark Res ; 9(1): 24, 2021 Apr 12.
Article in English | MEDLINE | ID: mdl-33845905

ABSTRACT

BACKGROUND: Dalpiciclib (SHR6390) is a novel inhibitor of cyclin-dependent kinase 4/6 which demonstrated promising anti-tumor potency in preclinical models. This first-in-human study was conducted to evaluate the tolerability, pharmacokinetics, safety, and preliminary antitumor activity of dalpiciclib in patients with advanced breast cancer (ABC). METHODS: In this open-label, phase 1 study, Chinese patients who had failed standard therapy were enrolled to receive oral dalpiciclib in 3 + 3 dose-escalation pattern at doses of 25-175 mg. Eligible patients were given a single-dose of dalpiciclib in week 1, followed by once daily continuous doses for 3 weeks, and 1 week off in 28-day cycles. Based on the tolerability, pharmacokinetics, and activity data revealed from the dose-escalation phase, three dose cohorts were selected to expand to 8-10 patients. The primary endpoints were maximum tolerated dose (MTD) and pharmacokinetics. RESULTS: Between Apr 15, 2016 and Dec 21, 2018, 40 patients were enrolled; all were diagnosed of hormone receptor-positive and HER2-negative ABC. Dalpiciclib 100 mg, 125 mg, and 150 mg cohorts were expanded to 10 patients. No dose-limiting toxicity was observed and the MTD was not reached. Adverse events (AEs) of grade 3 or 4 were observed in 22 (55.0%) of 40 patients, being neutropenia (52.5%), leukopenia (35.0%), thrombocytopenia (5.0%), and hypertension (2.5%). No serious AEs were reported. At the doses of 50-175 mg, steady state areas under the concentration-time curve and peak concentration increased almost proportionally with dose. The disease control rate (DCR) was 62.5% (25/40, 95% CI: 45.8-77.3). Two patients (5%; 125 mg and 150 mg cohorts) achieved partial response, with responses lasting 169 and 356+ days, respectively. Among the three expansion cohorts, the 150 mg cohort had the numerically highest DCR of 80.0% (95% CI: 44.4-97.5) and longest median progression-free survival of 8.4 months (95% CI: 2.1-not reached). CONCLUSIONS: Dalpiciclib showed acceptable safety profile and dose-dependent plasma exposure in Chinese patients with ABC. The recommended phase 2 dose was 150 mg. Preliminary evidence of clinical activity was observed, which warrants further validation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02684266 . Registered Feb 17, 2016.

9.
Article in Chinese | MEDLINE | ID: mdl-33254319

ABSTRACT

Objective:The study is aimed to evaluate impacts of cochlear implantation on speech perception and quality of life in postlingual deaf adults, and to explore the correlation between speech perception and quality of life using Nijimegen Cochlear Implantation Questionnaire and Mandarin version of Minimum Speech Test Battery. Method:Thirty-six postlingual deafpatients were recruited, including 20 males and 16 females. Patient age was 20 to 72 years old(52±16) when CI was implanted, and the hearing loss duration was 2 to 25 years(14±6) before cochlear implantation. The single syllable recognition rate score were tested by using Mandarin version of Minimum Speech Test Battery, and the quantify quality of life was tested by using Nijimegen Cochlear Implantation Questionnaire. Result:Speech recognition and quality of life have significantly improved in patients with CI after cochlear implantiont. The scores of basic sound perception, advanced sound perception, speech ability, self-confidence, social activity ability, and social ability have improved, but the differences were not statistically significant. The Mandrin single-syllable recognition rate scores were related to basic sound perception(r=-0.36; P=0.004), advanced sound perception(r=-0.41; P=0.002), and speech ability(r=-0.67; P=0.001), and the differences are statistically significant. Conclusion:The postlingual deafnesses ability of auditory, speech perception and the quality of life have improved significantly in patients with CI after cochlear implantiont.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Aged , Female , Humans , Male , Middle Aged , Quality of Life , Speech , Young Adult
10.
J Mol Neurosci ; 70(9): 1445-1450, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32468216

ABSTRACT

Emerging evidence has suggested that patients with ischemic stroke (IS) and/or transient ischemic attack (TIA) are more likely to exhibit myocardial disorders, which can be reflected by transthoracic echocardiography (TTE). ATP binding cassette transporter 1 (ABCB1) plays an important role in the development and progression of atherosclerotic pathology. The objective of the current study was to investigate the associations of ABCB1 C3435T polymorphism with echocardiographic performances among patients with acute ischemic stroke. Patients with IS or TIA, who were hospitalized and received TTE between October 2016 to March 2019, were enrolled in this study. Demographic data and echocardiographic parameters of each participant were recorded. We included 122 patients, with the respective distribution of 12.30%, 48.36%, and 39.34% in CC, CT, and TT genotypes. There were significant differences among the three ABCB1 types, with respect to RV (P = 0.036). The presence of the TT genotype was associated with increased MVE (OR = 0.13, P = 0.02) but correlated with decreased RV (OR = -1.46, P = 0.02). Our study indicated that ABCB1 C3435T polymorphism is associated with echocardiographic parameters among patients with acute ischemic stroke. The presence of the TT genotype is associated with diastolic function and cardiac hypertrophy.


Subject(s)
Atherosclerosis/genetics , Ischemic Attack, Transient/genetics , Ischemic Stroke/genetics , Polymorphism, Single Nucleotide , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Atherosclerosis/diagnostic imaging , Female , Humans , Ischemic Attack, Transient/diagnostic imaging , Ischemic Stroke/diagnostic imaging , Male , Middle Aged
11.
J Glob Oncol ; 3(6): 692-700, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29244994

ABSTRACT

Purpose We aimed to quantify Chinese cancer survivors' perceived needs for survivorship care and to evaluate whether these needs could impact their willingness to use traditional Chinese medicine (TCM). Methods We conducted a cross-sectional survey with members of the Beijing Anti-Cancer Association in China. We measured perceived needs with the seven-item Brief Chinese Cancer Survivorship Needs Scale that assesses psychological, functional, nutritional, social, body image, pain, and symptom needs. The outcome variable was willingness to use TCM for survivorship care. We performed multivariable logistic regression analyses to evaluate whether perceived needs are associated with willingness. Results A total of 600 patients were invited, with a response rate of 81%. The mean (standard deviation) score of the perceived needs scale (0 to 10) was 4.4 (2.2), with the majority of participants endorsing nutritional (72%), symptom (65%), and psychological (54%) needs. Among survivors, 387 (80%; 95% CI, 76% to 83%) were willing to use TCM for survivorship care. In multivariable analysis, a higher perceived needs score (adjusted odds ratio [OR], 1.33; 95% CI, 1.14 to 1.56; P < .001) was associated with greater willingness to use TCM. Specifically, nutritional (OR, 3.17; 95% CI, 1.79 to 5.62; P < .001) and symptom needs (OR, 3.15; 95% CI, 1.79 to 5.55; P < .001) had the strongest relationship. Conclusion A higher level of perceived needs, especially in the areas of nutrition and symptoms, was associated with greater willingness to use TCM for survivorship care.


Subject(s)
Medicine, Chinese Traditional/methods , Needs Assessment , Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Cancer Survivors , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Survivorship , Young Adult
12.
Eur J Pharm Sci ; 49(4): 629-36, 2013 Jul 16.
Article in English | MEDLINE | ID: mdl-23727058

ABSTRACT

This work aimed to improve the clinical application of Radix Ophiopogonis polysaccharide (ROP), a natural anti-myocardial ischemic fructan with Mw of 4.80 kDa, by mono-PEGylation. Three mono-PEGylated ROPs were prepared by a moderate coupling reaction between amino-terminated methoxy-PEG (20-, 30-, or 40-kDa) and excessive hydroxyl-activated ROP. After being fully characterized by proton nuclear magnetic resonance as well as high-performance gel permeation chromatography and anthrone-sulfuric acid colorimetry coupled assay, they were evaluated for pharmacokinetics and anti-myocardial ischemic activities in rats with coronary artery ligation. The results showed that mono-PEGylated ROPs were successfully and effectively prepared. Compared with ROP, the three mono-PEGylated ROPs showed approximately 32-, 85-, and 100-fold prolonged retention in systemic circulation with plasma half-lives reaching 16.1, 42.4, and 49.8 h, respectively. Studies on anti-myocardial ischemic effects of the conjugates showed that administrated at the same molar dose of 4 µ mol/kg per injection as ROP, they could achieve comparable or even better therapeutic effects although their administration intervals were 2- to 6-fold longer than that of ROP. These findings confirm that PEGylation would be a promising approach to markedly reducing the injection-administered frequency of ROP and hence patient compliance without sacrifice of the therapeutic efficacy by significantly improving its pharmacokinetics.


Subject(s)
Cardiotonic Agents/therapeutic use , Liliaceae , Myocardial Ischemia/drug therapy , Polysaccharides/therapeutic use , Animals , Arterial Pressure/drug effects , Cardiotonic Agents/chemistry , Cardiotonic Agents/pharmacology , Creatine Kinase/blood , Heart Rate/drug effects , L-Lactate Dehydrogenase/blood , Male , Malondialdehyde/blood , Myocardial Ischemia/blood , Myocardial Ischemia/physiopathology , Phytotherapy , Plant Preparations , Plant Roots , Polyethylene Glycols/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/blood
13.
Eur J Pharm Sci ; 46(5): 545-52, 2012 Aug 15.
Article in English | MEDLINE | ID: mdl-22525436

ABSTRACT

PEGylation now plays an important role in drug delivery and is considered as the method of choice for improving the pharmacokinetics and stability of parenteral agents. However, its application in treating cardiac diseases is still limited. To guide the design of PEGylation for drug delivery to ischemic myocardium, the effects of the molecular weight of PEG and the myocardial ischemic conditions on PEG levels in plasma and myocardium were studied in this work following intravenous administration of fluorescein isothiocyanate-labeled 20- and 40-kDa mPEGs to mice with normal and ischemic myocardium. The results show that myocardial ischemia caused some consistent changes in pharmacokinetic parameters of mPEGs. Due to the enhanced permeability and retention (EPR) effect caused by ischemia, the distribution of 20- and 40-kDa mPEGs in ischemic hearts was approximately 1.47- and 1.92-fold higher than that in normal hearts, respectively. Under the same heart condition (either normal or ischemic), the cardiac AUC(0.5-24h)s of the two mPEGs were comparable, although their plasma AUCs differed by nearly 4-fold; however, a smoother cardiac level-time profile was achieved by 40-kDa mPEG. This study addressed the relative importance of the EPR effect of ischemic zones and the molecular size of PEG in cardiac drug delivery, which is believed to be helpful for macromolecular drug design.


Subject(s)
Drug Carriers , Fluorescein-5-isothiocyanate/pharmacokinetics , Myocardial Ischemia/metabolism , Myocardium/metabolism , Polyethylene Glycols/pharmacokinetics , Animals , Area Under Curve , Chemistry, Pharmaceutical , Disease Models, Animal , Fluorescein-5-isothiocyanate/administration & dosage , Fluorescein-5-isothiocyanate/chemistry , Male , Mice , Molecular Weight , Permeability , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemistry , Technology, Pharmaceutical , Tissue Distribution
14.
J Biomater Sci Polym Ed ; 22(4-6): 429-41, 2011.
Article in English | MEDLINE | ID: mdl-20566038

ABSTRACT

Although poly(ethylene glycol) and polysaccharide have been widely used as pharmaceutical carriers for decades, they both have some disadvantages. In order to overcome these shortcomings, this study was conducted to prepare and assess a novel polymeric carrier, PEGylated inulin. Three conjugates, with an average of 1.4 PEG (20 kDa), 3.1 PEG (20 kDa) and 5.5 PEG (5 kDa) residues per single inulin (5 kDa) molecule, respectively, were prepared through the reaction of hydroxyl-activated inulin with amino-terminated methoxy-PEGs. Their pharmacokinetic properties were evaluated in rats following i.v. and s.c. administration. These conjugates, following i.v. administration, displayed multi-compartmental pharmacokinetics with the mean retention times being 9.8, 80 and 90 h, respectively. When given subcutaneously, they were well absorbed with the absolute bioavailability ranging from 66% to 79% and the mean retention times being 35, 155 and 179 h, respectively. Both the small size and the long circulation lifetime suggest their potential application as a pharmaceutical carrier to enhance the delivery of various agents to their targets by the enhanced permeability and retention (EPR) effect.


Subject(s)
Drug Carriers/chemistry , Inulin/chemistry , Polyethylene Glycols/chemistry , Animals , Drug Carriers/pharmacokinetics , Drug Delivery Systems/methods , Inulin/pharmacokinetics , Male , Molecular Structure , Polyethylene Glycols/pharmacokinetics , Rats , Rats, Sprague-Dawley , Reproducibility of Results
15.
Yao Xue Xue Bao ; 45(7): 827-32, 2010 Jul.
Article in Chinese | MEDLINE | ID: mdl-20931778

ABSTRACT

The ischemic heart disease has been endangering human health seriously. Although there are many kinds of anti-ischemic drugs, most of them are lacking in tissue specificity, which together with a remarkably reduced blood circulation in the ischemic zone often lead to a quite low drug distribution in the targets. Myocardial ischemia can cause a lot of pathophysiological changes, such as the enhanced permeability of the endothelial cell membrane, the up-regulated expression of various cell adhesion molecules on endothelium, the exposure of intracellular antigenic components, the decrease of pH within the ischemic zone, and so on. To date, some of these changes have been exploited with limited success to gain the passive, active and physicochemical targeting of diagnostic or therapeutic drugs to myocardial ischemic regions. However, more effective delivery strategies are still eagerly needed. Here, we reviewed and discussed the potential targeting-delivery mechanisms and strategies, used or may be used in the future, for myocardial ischemic regions.


Subject(s)
Capillary Permeability , Drug Delivery Systems/methods , Liposomes , Myocardial Ischemia/therapy , Myocardium/metabolism , Animals , Antibodies, Monoclonal/immunology , Drug Carriers , Genetic Therapy , Humans , Liposomes/chemistry , Liposomes/metabolism , Myocardium/pathology , Polyethylene Glycols/metabolism , Ultrasonics
16.
Eur J Pharm Biopharm ; 76(2): 230-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20633648

ABSTRACT

Radix Ophiopogonis polysaccharide (ROP), a natural graminan-type fructan with Mw of ∼5kDa, had been found to have an excellent anti-myocardial ischemic activity. However, its rapid renal excretion following administration remarkably limits its efficacy and clinical use, which makes necessary the development of an effective delivery system. In this article, the feasibility of PEGylation to solve this problem was examined. A moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG was chosen to PEGylate ROP. Five different mPEG-ROP conjugates (with mPEG of molecular mass 2, 5 or 20kDa) were prepared, purified, characterized and evaluated in pharmacokinetics and in vitro bioactivity. Results showed that only when the apparent molecular weight of the conjugate approached to a certain value, would its plasma elimination reduce abruptly. In general, the conjugation caused the reduction in the bioactivity of ROP; however, well-preserved bioactivity was observed when the grafting degree of the conjugate was lower. Among the five conjugates studied, the one with an average 1.3 mPEG (20kDa) residues per single ROP was found to be satisfactory both in plasma retention and in bioactivity. It had a 47.4-fold increased elimination half-life and preserved approximately 74% of the bioactivity of ROP; moreover, the decrease in bioactivity is not significant. These findings demonstrate that PEGylation would be a promising approach for improving the clinical efficacy of ROP by prolonged retention in plasma.


Subject(s)
Endothelial Cells/drug effects , Ophiopogon/chemistry , Polyethylene Glycols/chemistry , Polysaccharides/pharmacology , Animals , Cells, Cultured , Endothelial Cells/metabolism , Feasibility Studies , Half-Life , Humans , Male , Molecular Weight , Plant Extracts/pharmacokinetics , Plant Extracts/pharmacology , Polysaccharides/isolation & purification , Polysaccharides/pharmacokinetics , Rats , Rats, Sprague-Dawley , Time Factors
17.
Biomed Chromatogr ; 24(8): 820-5, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20020416

ABSTRACT

Interest in antimyocardial ischemic activity of a graminan-type fructan with a weight average molecular weight of 4.8 kDa extracted from Radix Ophiopogonis (ROP) has necessitated the study of its pharmacokinetics and tissue distribution. For that, a simple HPGPC-FD method was developed for the sensitive and specific determination of FITC-ROP (fluorescein-isothiocyanate-labeled ROP) in plasma and rat tissues (heart, liver, spleen, lung, kidney, brain and stomach). The analyte was separated on a Shodex Sugar KS-802 high-performance gel column with 0.1 M phosphate buffer (pH 7.0) as mobile phase at a flow rate of 0.5 mL/min, and fluorescence detection at lambda(ex) 495 nm and lambda(em) 515 nm. The calibration curve for FITC-ROP was linear over the range 0.25-20.0 or 50.0 microg/mL in all studied biosamples with correlation coefficients > 0.995. The inter-day and intra-day precisions of analysis were not more than 10%, and assay accuracy ranged from 93 to 105% for plasma and from 89 to 108% for tissue homogenates. This method has been confirmed here to be suitable for the study of pharmacokinetics and tissue distribution of ROP and the achieved results are highly instructive for the further pharmaceutical development of ROP, suggesting the promising application of the method to the increasingly important carbohydrate-based drugs.


Subject(s)
Chromatography, High Pressure Liquid/methods , Fructans/analysis , Fructans/pharmacokinetics , Ophiopogon/chemistry , Plant Extracts/pharmacokinetics , Animals , Chromatography, High Pressure Liquid/instrumentation , Male , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Tissue Distribution
18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 26(1): 53-5, 2008 Feb.
Article in Chinese | MEDLINE | ID: mdl-18357884

ABSTRACT

OBJECTIVE: To choose the best retraction agent for the clinic by evaluating the gingival inflammation related to three kinds of retraction agents. METHODS: 40 maxillary premolars were divided into four groups according to the randomized block design: Ferric sulfate group, aluminum chloride group, epinephrine group, sodium chloride group(control group), each 10 teeth, respectively used 25% AlCl3, 15.5% Fe2(SO4)3, 0.1% HCl-epinephrine, sodium chloride as retraction agents. The quantity of gingival crevicular fluid (GCF) and the active level of aspartate amino-transferase (AST) in gingival crevicular fluid were measured before and 1, 3, 5, 7, 9 days after retracting gingiva by four kinds retraction agents. The changes of GCF were calculated. RESULTS: The change of the GCF from the smallest to the largest was sodium chloride, 0.1% HCl-epinephrine, 25% AlCl,, 15.5% Fe2 (SO)3. Compared with sodium chloride, only 15.5% Fe2 (SO)3 in AST was the significant difference in the first day and the third day (P < 0.05). AST of ferric sulfate group after 1, 3 days greater than 800 IU. CONCLUSION: 0.1% HCl-epinephrine is suggested in patient without cardiovascular disease. For patient with cardiovascular disease, the better substitute is 25% AlCl3. 15.5% Fe2 (SO4)3 will not be used until its concentration is fallen.


Subject(s)
Gingiva , Gingival Crevicular Fluid , Aluminum Chloride , Aluminum Compounds , Chlorides , Epinephrine , Humans , Incisor , Inflammation
19.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 42(8): 501-4, 2007 Aug.
Article in Chinese | MEDLINE | ID: mdl-18001597

ABSTRACT

OBJECTIVE: To investigate the variation of the corrosion resistance of micro-arc oxidation film on titanium by electrochemical methods in simulated body fluid. METHODS: Micro-arc oxidation film was formed on the titanium surface using micro-arc oxidation. The morphology was observed with scanning electron microscopy (SEM) and the phase composition was analyzed using X-ray diffraction (XRD). Polarization curves and electrochemical impedance spectroscopy (EIS) in simulated body fluid were examined with electrochemical methods. RESULTS: On the titanium surface with micro-arc oxidation, the film consisted of many volcanic micropores. The film formed was a titanium dioxide (TiO(2)) with peaks for both anatase and rutile phases. In addition, hydroxylapatite was also observed. The self-corrosion potential and self-corrosion current density of titanium with micro-arc oxidation film were -0.255 V and 0.80 microA/cm(2) respectively, while those of untreated titanium were -0.358 V and 0.55 microA/cm(2). Electrochemical impedance spectroscopy confirmed the model of equivalent circuits reasonable. CONCLUSIONS: The results of electrochemical examinations indicate that micro-arc oxidation film increases the corrosion resistance of titanium.


Subject(s)
Titanium/chemistry , Corrosion , Durapatite/chemical synthesis , Electrochemistry , Oxidation-Reduction
20.
Shanghai Kou Qiang Yi Xue ; 16(3): 295-8, 2007 Jun.
Article in Chinese | MEDLINE | ID: mdl-17660918

ABSTRACT

PURPOSE: To examine the corrosion resistance of micro-arc oxidation film on titanium by electrochemical methods in simulated body fluid. METHODS: Micro-arc oxidation film was formed on titanium surface by using micro-arc oxidation. The morphology, phase composition and the surface roughness were observed by scanning electron microscopy (SEM), X-ray diffraction(XRD) and profilemeter, respectively. Polarization curves in simulated body fluid was examined by electrochemical methods. SPSS11.0 software package was used for one-way ANOVA. RESULTS: On titanium surface with micro-arc oxidation, the film was consisted of many volcanic microporous, about 0.1microm -5microm in diameter. The film formed was a titanium oxide (TiO(2)) with peaks for both anatase and rutile phases, in addition, hydroxylapatite was also observed. Roughness increased on titanium surface. The self-corrosion potential and self-corrosion current density of titanium with micro-arc oxidation film were -0.255V and 0.80microA/cm(2) respectively, while those of untreated titanium were -0.358V and 0.55microA/cm(2). CONCLUSIONS: The results of electrochemical examinations indicate that micro-arc oxidation film increases the corrosion resistance of titanium.


Subject(s)
Corrosion , Titanium , Body Fluids , Dental Materials , Microscopy, Electron, Scanning , Oxidation-Reduction
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