Co-delivery of antineoplastic and protein drugs by chitosan nanocapsules for a collaborative tumor treatment.

Although combination delivery (co-delivery) shows much superiority in the defect compensation of single-agent therapy, the construction and application of co-delivery systems are still challenging, especially for protein-based joint systems. In this work, a series of chitosan (CS)-amino acid derivatives (Arg-CS, Lys-CS, and Phe-CS) with different degrees of substitution (DS) were synthesized to prepare CS nanocapsules (CNCs) using a simple emulsification method in the presence of linoleic acid (LA). The hydrophobic drug can be loaded in LA droplets, and a positively charged protein stabilized the optimized Arg-CS nanocapsules (Arg-CNCs) on their negative surfaces. The in vitro antitumor efficacy of Arg-CNCs co-delivering paclitaxel and recombinant human caspase-3 was evaluated in HeLa cells. The co-delivery system displayed much lower IC50 values and a higher percentage of apoptotic cells compared with the control groups. This system provides a promising and universal strategy for co-delivery, leading to collaborative tumor treatment.

[Clinical features and StAR gene mutations in children with congenital lipoid adrenal hyperplasia].

This article reported the clinical manifestations, steroid profiles and adrenal ultrasound findings in two unrelated Chinese girls with lipoid congenital adrenal hyperplasia (LCAH). Direct DNA sequencing and restriction fragment length polymorphism (RFLP) analysis were used to identify the mutations of steroidogenic acute regulatory protein (StAR) gene. The two patients with 46,XX karyotype, presented hyperpigmentation, growth retardation, and hyponatremia. Steroid profiles analysis revealed elevated plasma adrenocorticotrophic hormone levels, decreased or normal serum cortisol levels and low levels of androgens. Ultrasound examinations revealed that enlarged adrenals in patient 1 and normal adrenals in patient 2. Direct DNA sequencing of StAR gene showed a reported homozygous for c.772C>T(p.Q258X) in patient 1. Compound heterozygous for c.367G>A(p.E123K) and IVS4+2T>A (both novel mutations) were found in patient 2, inherited from her mother and father respectively. The amino acid of mutant position of the novel p.E123K was highly conserved in ten different species and was predicted to have impacts on the structure and function of StAR protein by the PolyPhen-2 prediction software. RFLP analysis revealed three bands (670, 423 and 247 bp) in patient 2 and her father and two bands (423 and 247 bp) in her mother and 50 controls. It is concluded that LCAH should be considered in girls with early onset of adrenal insufficiency and that steroid profiles, karyotype analysis, adrenal ultrasound and StAR gene analysis may be helpful for the definite diagnosis of LCAH.

[Diagnosis of Muscular Dystrophy Using Western Blot with Micro-sample of Muscle].

OBJECTIVE: To diagnose muscular dystrophy using Western blot (WB) by improving the method of the protein extraction. METHOD: Firstly,we compared the effect of different sample buffer solutions and processing Methods on the extraction of muscle protein in rats,then selected the appropriate extracting method and the process of the muscular protein. RESULTS: We put the selected sample buffer into the micro-sample,then mixed. The concentration of the extracting protein was much more,and the loss during the process was much less. We extracted enough protein in 62 cases. The protein bands were showed clearly by WB,and the abnormal protein bands were shown in some patients. Compared with the Results of immunohistochemical staining detected the severe abnormal expressions of Dys-R,Dys-C,and Dys-N in the specimens,we did not detect the corresponding target band in WB. We detected the target protein band of the specimens were abnormal position,light or normal staining in WB,while Dys were mildly expressed in immunohistochemical staining. CONCLUSIONS: The improved protein extraction method can save the muscle tissue,and the protein bands can be used for diagnosing the muscular dystrophy. For clinically suspected patients with dystrophinopathy,if normal or mild deficiency is shown by immunohistochemistry,WB should be applied to detect the dystrophin protein band.

The performance of thiol-terminated PEG-paclitaxel-conjugated gold nanoparticles.

A series of thiol-terminated polyethylene glycol (PEG)-paclitaxel (PTX) derivatives are designed and synthesized to fabricate PTX-conjugated gold nanoparticles (PTX@GNPs) and improve their overall performance. By extending the molecular weight of PEG from 400 to 1000 Da, the optimized water solubility of the conjugate reaches 184 mg/mL, equal to 4.6 × 10(5) times that of PTX alone (0.4 µg/mL). High drug loading is obtained by eliminating the steric hindrance between PTX molecules on the surface of GNPs. The gold conjugate shows double simultaneous stimulation-induced drug release behavior in the presence of both esterase and high concentrations of glutathione. The synergic release characteristics of this conjugate results in significant performance improvements, including prolonged circulation due to high stability in vivo, targeted release of PTX inside tumor cells, and increased tumor cell killing efficiency. Improving the in vitro properties of the conjugate not only significantly enhances its therapeutic efficacy in a murine liver cancer model, but also allows drug-conjugated gold nanoparticles to be used as a promising nanoprodrug system in the cancer therapeutics.

Neuroendocrine and haemodynamic changes in single-lead atrial pacing and dual-chamber pacing modes.

OBJECTIVES: Neuroendocrine and haemodynamic changes were compared between single-lead atrial (AAI) or dual-chamber (DDD) pacing modes in patients with sick sinus syndrome, in a crossover study. METHODS: Inpatients scheduled for their first pacemaker implantation were screened for the following inclusion criteria: sick sinus syndrome; intact atrioventricular conduction; normal QRS interval. All study patients were implanted with a dual-chamber pacemaker, programmed for AAI or DDD pacing mode. Patients were allocated randomly to AAI followed by DDD pacing or to DDD followed by AAI pacing, each mode being applied for 72 h. Echocardiographic, electrocardiographic and neuroendocrine parameters were tested at the end of each pacing mode. RESULTS: From 152 inpatients screened for inclusion, 28 were selected for treatment. Plasma levels of atrial natriuretic peptide (ANP), endothelin, aldosterone and angiotension II were significantly lower, and aortic flow velocity-time integral was significantly higher, in AAI mode than in DDD mode. Aortic pre-ejection interval, interventricular mechanical delay and QRS duration were significantly higher in DDD than in AAI mode. CONCLUSIONS: In patients with sick sinus syndrome, DDD pacing mode can induce neuroendocrine system activation, and left ventricular dysfunction and dyssynchrony. These findings discourage the routine use of DDD pacing in patients with sick sinus syndrome.

Computational approach to seasonal changes of living leaves.

This paper proposes a computational approach to seasonal changes of living leaves by combining the geometric deformations and textural color changes. The geometric model of a leaf is generated by triangulating the scanned image of a leaf using an optimized mesh. The triangular mesh of the leaf is deformed by the improved mass-spring model, while the deformation is controlled by setting different mass values for the vertices on the leaf model. In order to adaptively control the deformation of different regions in the leaf, the mass values of vertices are set to be in proportion to the pixels' intensities of the corresponding user-specified grayscale mask map. The geometric deformations as well as the textural color changes of a leaf are used to simulate the seasonal changing process of leaves based on Markov chain model with different environmental parameters including temperature, humidness, and time. Experimental results show that the method successfully simulates the seasonal changes of leaves.

[Impact of proton pump inhibitor omeprazole on the antiplatelet effect of clopidogrel in individuals with various CYP2C19*2 genotypes].

OBJECTIVE: To investigate the impact of omeprazole on platelet response to clopidogrel and the effect of polymorphisms of CYP2C19 on the antiplatelet effect of clopidogrel. METHODS: Platelet aggregation (PA) was assessed before 300 mg aspirin plus 300 mg loading dose of clopidogrel and after 300 mg aspirin plus 75 mg maintenance dose of clopidogrel 7 days later in 414 patients with acute coronary syndrome who have undergone percutaneous coronary intervention (PCI). Thereafter, gastric mucosal protective drugs were given (omeprazolem 20 mg, n=224 or cimetidine 800 mg, n=190). Fourteen days later, PA was measured again. Genotypes of CYP2C19*2 were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: After taken aspirin and clopidogrel, PA has decreased significantly in both groups. Compared with cimetidine, omeprazole had no significant impact on PA on 7 and 21 days post PCI. Compared with homozygotes or heterozygotes for the wild-type CYP2C19*2, patients with CYP2C19*2 AA genotype had significantly higher PA on 7 and 21 days post PCI (P<0.05). CONCLUSION: No attenuating effect on platelet response to clopidogrel has been observed for Omeprazole. The variant of CYP2C19*2 AA genotype is significantly associated with attenuated response to clopidogrel.

Determinants of quality of life in people with epilepsy and their gender differences.

Improving the patient's quality of life (QOL) is the most important goal of epilepsy management. We performed this study to determine the factors associated with QOL in people with epilepsy and to assess whether there are gender differences in these determinants. Patients were interviewed using the Quality of Life in Epilepsy Inventory-31(QOLIE-31), the Adverse Event Profile (AEP), the Self-Rating Anxiety Scale (SAS), and the Hamilton Depression Rating Scale (HAMD). Two hundred forty-seven patients (152 men, 95 women) were included in the analysis. Among all patients, regressive analyses showed that AEP score was the strongest predictor of the QOLIE-31 overall score, accounting for 10.4% of the variance. The next strongest predictors were the number of currently used antiepileptic drugs (AEDs) (3.6%), the HAMD score (2.5%), and the SAS score (1.2%). Importantly, there were gender differences in these predictors of QOL. The strongest predictors of the QOLIE-31 overall score in women were the AEP score and the number of AEDs. In contrast, the strongest predictors in men were the SAS score, the AEP score and the frequency of seizures. These results indicate that perceived adverse effects of treatments and number of AEDs exerted greater effects on QOL in women, whereas anxiety and seizure-related variables had a stronger impact on QOL among men. Accordingly, it may be necessary to individualize interventions to improve the QOL of people with epilepsy.

[Upgrading to resynchronization therapy in patients with heart failure after chronic right ventricular apical pacing].

OBJECTIVE: To investigate the clinical efficacy of cardiac resynchronization therapy (CRT) through biventricular pacing in chronically right ventricular apical paced patients with heart failure. METHODS: Ten chronically right ventricular apical paced patients with left ventricular ejection fraction (EF) ≤ 35% underwent CRT upgrading. And the follow-up period was over 12 months. Seven of them reported a significant improvement in their symptoms. Two patients died and one patient had no response. As compared with pre-CRT, CRT significantly improved NYHA classification, decreased left atrium diameter [(43 ± 5) mm vs (46 ± 7) mm], pulmonary arterial pressure [(42 ± 6) mm Hg vs (54 ± 13) mm Hg] and BNP [(184 ± 73) ng/L vs (545 ± 286) ng/L] (P < 0.05), improved left ventricular EF [(35 ± 5)% vs (32 ± 4)%]. Tissue Doppler imaging revealed the maximal difference of time to peak myocardial systolic contraction of 12 left ventricular segment shortened [(136 ± 28) ms vs (97 ± 18) ms], interventricular mechanical delay shortened [(52 ± 5) ms vs (31 ± 6) ms)] after upgrading. CONCLUSION: CRT upgrading from right ventricular apical pacing may improve left ventricular function in patients with heart failure.

Coexistence of 2 types of atrial tachycardias and right ventricular outflow tract tachycardia.

Double tachycardia is a relatively uncommon type of tachycardia. In this report, we discuss a 68-year-old woman with history of frequent palpitations. Electrophysiologic study revealed that narrow QRS tachycardias from 2 origins and 1 wide QRS tachycardia were induced and each of the tachycardias was induced by the other. We found that 2 focal atrial tachycardias and 1 ventricular tachycardia originated from right ventricular outflow tract. All of these tachycardias were successfully ablated during one session, and no recurrence appeared during 10 months of follow-up.

[Factors associated with quality of life in epileptics and the variations between men and women, younger and older people].

OBJECTIVE: To determine factors associated with quality of life (QOL) in epileptics and the variations between men and women, younger and older people. METHODS: A total of 204 patients (160 younger, 49 older; 125 men, 79 women) were interviewed by the quality of life in epilepsy-31 (QOLIE-31), side effect profile (SEP), self-rating anxiety scale (SAS) and Hamilton depression scale (HAMD). Medical and socio-demographic data were acquired from patient records. Multivariate linear regressive analyses were used to determine the set of best predictors of composite QOLIE-31 score. RESULTS: No statistical difference was revealed in QOLIE-31 overall score either between younger and older patients or between men and women. Among all patients, regressive analyses revealed that SEP (beta = - 0.395, P = 0.000) and SAS (beta = -0.152, P = 0.016) were two strong predictors of QOLIE-31 overall score. Grouped by gender, among men, epilepsy duration (beta = -0.165, P = 0.028) and seizure frequency (beta = -0.284, P = 0.001) respectively associated with QOLIE-31 overall score and "social function" score while the number of AEDs (antiepileptic drugs) substantially correlated with QOLIE-31 overall score among women (beta= -0.238, P = 0.006). Grouped by ages, seizure frequency (beta = -0.284, P = 0.000) and education level (beta = 0.203, P = 0.005) predicted QOLIE-31 "social function" score only among younger patients; among older patients, a significant association were found between the number of AEDs and QOLIE-31 overall score (beta = - 0.363, P = 0.004). CONCLUSION: Side effects of AEDs and number of AEDs exert greater effect on QOL in women and older patients. And such seizure-related variables as epileptic duration and seizure frequency influence QOL only among men and younger patients.

Quality of life and related factors in Chinese adolescents with active epilepsy.

BACKGROUND: Studies from developed countries illustrate that adolescents with epilepsy have a higher frequency of behavioral problems than healthy or chronically ill control groups. In China, where public perception of epilepsy is relatively unfavorable, the impairment of quality of life (QOL) and its related risk factors in adolescents with epilepsy is unknown. METHODS: To identify the level of QOL and related factors among adolescents with epilepsy in China, we conducted a case-control study of 47 pairs of active adolescents with epilepsy and matched normal controls. QOL of adolescents with epilepsy was measured with the Chinese version of the "Quality of Life in Epilepsy Inventory for Adolescents 48 (QOLIE-AD-48)". Three domains unrelated to epilepsy (memory/concentration, physical functioning and social support) were used to evaluate QOL of a control group. RESULTS: The mean total score of QOLIE-AD-48 of epileptic subjects was 65.6+/-14.1. Aspects of memory/concentration, physical functioning and social support of adolescent patients were generally impaired compared with those of normal controls. Age of onset, seizure worry, and fear of injury were all significantly associated with QOL. CONCLUSIONS: More attention should be paid to the seizure-related psychological status of adolescents with epilepsy to improve QOL at their transitional stage of physical and mental human development.