PubMed Health⌕ Search

Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 19 recordsLinked to original sources
PubMed2007

Incidence of changes and predictive factors for sexual function after coronary stenting.

The study was aimed at determining the incidence of changes in sexual function and identifying the possible associated variables of erectile dysfunction (ED) in coronary artery disease (CAD) patients undergoing coronary stenting. Four hundred and sixty-seven patients were retrospectively contacted with a questionnaire regarding sexual function from 6 months pre-stenting to 6 months post-stenting by telephone follow up. Univariate analyses were used to determine prognostic variables. ED changed following stenting in CAD (P < 0.05), in acute coronary syndrome (ACS) (P > 0.05) and in chronic coronary syndrome (CCS) (P < 0.05). Sexual activity was not resumed in 8.1%, was unchanged in 33.8%, increased in 0% and decreased in 58.0%. The average frequency of sexual activity decreased every month in CAD (P < 0.05), in ACS (P < 0.05) and in CCS (P < 0.01) after undergoing coronary stenting respectively. The mean time interval between the onset of ED and CAD was 33 months. Resuming sexual activity after stenting varied from 2 weeks to 30 months. Significant predictors of ED after coronary stenting were mean age, diabetes mellitus, 2,3-vessel disease or current smoking status. It was concluded that coronary stenting had a significant incidence of ED. Mean age, diabetes mellitus, 2,3-vessel disease or current smoking status showed to be the main variables associated with ED. Attempts to improve individual secondary prevention outcomes (controlling serum glucose and smoking cessation) should be designed.

Coronary Artery Disease↗
PubMed2006

Future carbon balance of China's forests under climate change and increasing CO2.

The possible response of the carbon (C) balance of China's forests to an increase in atmospheric CO(2) concentration and climate change was investigated through a series of simulations using the Integrated Terrestrial Ecosystem Carbon (InTEC) model, which explicitly represents the effects of climate, CO(2) concentration, and nitrogen deposition on future C sequestration by forests. Two climate change scenarios (CGCM2-A2 and -B2) were used to drive the model. Simulations showed that China's forests were a C sink in the 1990 s, averaging 189 Tg C yr(-1) (about 13% of the global total). This sink peaks around 2020 and then gradually declines to 33.5 Tg C yr(-1) during 2091-2100 without climate and CO(2) changes. Effects of pure climate change of CGCM2-A2 and -B2 without allowing CO(2) effects on C assimilation in plants might reduce the average net primary productivity (NPP) of China's forests by 29% and 18% during 2091-2100, respectively. Total soil C stocks might decrease by 16% and 11% during this period. China's forests might broadly act as C sources during 2091-2100, with values of about 50 g Cm(-2)yr(-1) under the moderate warming of CGCM2-B2 and 50-200 g Cm(-2)yr(-1) under the warmer scenario of CGCM2-A2. An increase in CO(2) might broadly increase future C sequestration of China's forests. However, this CO(2) fertilization effect might decline with time. The CO(2) fertilization effects on NPP by the end of this century are 349.6 and 241.7 Tg C yr(-1) under CGCM2-A2 and -B2 increase scenarios, respectively. These effects increase by 199.1 and 126.6 Tg C yr(-1) in the first 50 years, and thereafter, by 150.5 and 115.1 Tg C yr(-1) in the second 50 years under CGCM2-A2 and -B2 increase scenarios, respectively. Under a CO(2) increase without climate change, the majority of China's forests would be C sinks during 2091-2100, ranging from 0 to 100 g Cm(-2)yr(-1). The positive effect of CO(2) fertilization on NPP and net ecosystem productivity would be exceeded by the negative effect of climate change after 2050. Under the CGCM2-A2 climate scenario and with direct CO(2) effects, China's forests may be a small C source of 7.6 Tg C yr(-1) during 2091-2100. Most forests act as C sources of 0-40 g Cm(-2)yr(-1). Under the CGCM2-B2 climate scenario and with direct CO(2) effects, China's forests might be a small C sink of 10.5 Tg C yr(-1) during 2091-2100, with C sequestration of most forests ranging from 0 to 40 g Cm(-2)yr(-1). Stand age structure plays a more dominant role in determining future C sequestration than CO(2) and climate change. The prediction of future C sequestration of China's forests is very sensitive to the Q(10) value used to estimate maintenance respiration and to soil water availability and less sensitive to N deposition scenario. The results are not yet comprehensive, as no forest disturbance data were available or predicted after 2001. However, the results indicate a range of possible responses of the C balance of China's forests to various scenarios of increase in CO(2) and climate change. These results could be useful for assessing measures to mitigate climate change through reforestation.

Atmosphere↗
PubMed2006

Carbon sinks and sources in China's forests during 1901-2001.

This paper reports the annual carbon (C) balance of China's forests during 1901-2001 estimated using the Integrated Terrestrial Ecosystem C-budget model (InTEC). Annual carbon source and sink distributions are simulated for the same period using various spatial datasets including land cover and leaf area index (LAI) obtained from remote sensing, soil texture, climate, forest age, and nitrogen deposition. During 1901-1949, China's forests were a source of 21.0+/-7.8 Tg C yr(-1) due to disturbances (human activities). Its size increased to 122.3+/-25.3 Tg C yr(-1) during 1950-1987 due to intensified human activities in the late 1950s, early 1960s, 1970s and early 1980s. The forests became large sinks of 176.7+/-44.8 Tg C yr(-1) during 1988-2001, owing to large-scale plantation and forest regrowth in previously disturbed areas as well as growth stimulation by nondisturbance factors such as climatic warming, atmospheric CO(2) fertilization, and N deposition. From 1901 to 2001, China's forests were a small carbon source of 3.32 Pg C, about 32.9+/-22.3 Tg C yr(-1). The overall C balance in biomass from InTEC generally agrees with previous results derived from forest inventories of China's forests. InTEC results also include C stock variation in soils and are therefore more comprehensive than previous results. The uncertainty in InTEC results is still large, but it can be reduced if a detailed forest age map becomes available.

Agriculture↗
PubMed2006

NOS2 (iNOS) deficiency in kidney donor accelerates allograft loss in a murine model.

Renal NOS2 is expressed and produces abundant nitric oxide (NO) in various renal cells in response to proinflammatory cytokines. However, the role of this enzyme in renal allograft survival remains unknown. Kidney allotransplantation was performed in the murine model of C57BL/6J (H-2(d)) to nephrectomized Balb/c (H-2(b)) mice. Here we show that deficiency in NOS2 expression in kidney donors significantly advanced allograft failure, indicated by decreasing mean survival of recipients receiving NOS2 null grafts (15.4 +/- 6.4 days) as compared to those with wild type grafts (65.4 +/- 28.1 days) (p = 0.0005). Consistent with survival results, NOS2 null grafts had more severe renal tubule injury and decreased renal function compared to wild type grafts. In vitro NOS2 expressing TEC had greater resistance to allogeneic lymphocyte-mediated apoptosis. The addition of exogenous NO inhibited Fas-mediated TEC apoptosis and reduced proliferation of allogeneic lymphocytes. These data suggest that endogenous production of NO through renal NOS2 activity can play a protective role in kidney grafts through attenuating Fas-mediated donor cell apoptosis as well as by inhibiting proliferation of inflammatory infiltrating lymphocytes. Enhanced donor NOS2 expression may be a useful strategy to improve kidney transplant survival.

Animals↗
PubMed2006

Evidence for a distinct group of nestin-immunoreactive neurons within the basal forebrain of adult rats.

Nestin is an intermediate filament protein serving as a marker for neuroprogenitor and stem cells. Here we report that a cluster of previously unrecognized nestin immunoreactive (nestin-ir) neurons was located in the medial septum-diagonal band of Broca (MS-DBB) of the basal forebrain in adult rats. Nestin-ir neurons were exclusively located in the MS-DBB and intermingled with choline acetyltransferase-ir (ChAT-ir), parvalbumin-ir (PV-ir), or nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactive (NADPHd-reactive) neurons. However, there was no colocalization between nestin-ir and PV-ir in single neurons in MS-DBB; only about 35% of nestin-ir neurons were ChAT-ir, and 8%-12% of nestin-ir neurons were NADPHd-reactive. Morphologically, nestin-ir neurons showed a larger size of somata than that of ChAT-ir or PV-ir neurons and the distribution of nestin-ir neurons spread across the rostro-caudal extent of the MS-DBB. Moreover, retrograde tracing revealed that a significant portion of these nestin-ir neurons projected to the thalamus and hippocampus. These results, for the first time, provide strong evidence that there exists a cluster of previously unrecognized nestin-ir neurons in MS-DBB of the basal forebrain in adult rats and that these nestin-ir neurons are distinguishable from ChAT-ir, PV-ir, and NADPHd-reactive neurons.

Acetylcholine↗
PubMed2006

GAL4-NF-kappaB fusion protein augments transgene expression from neuronal promoters in the rat brain.

Targeted gene expression mediated by a mammalian cellular promoter is desirable for gene therapy in the brain, where there are a variety of different neuronal phenotypes, several types of supportive cells, and blood vessels. However, this approach can be hampered by weak activity of some cellular promoters. In view of the potency of the transcription factor NF-kappaB in regulating neuronal gene expression, we have assessed whether it can be used to enhance the strength of neuron-specific promoters. Our approach was to use a neuronal promoter to drive expression of a chimeric transactivator, which consisted of a part of the transcriptional activation domain of the NF-kappaB p65 protein fused to the DNA-binding domain of GAL4 protein from yeast. The second copy of the neuronal promoter was modified by introducing the unique GAL4 binding sequences at its 5' end and used to drive the expression of a transgene. Binding of the chimeric transcriptional activator upstream of the second promoter was expected to potentiate its transcriptional activity. In this study, the approach was applied to the platelet-derived growth factor beta chain and synapsin-1 neuron-specific promoters and tested in vitro and in vivo using plasmid, lentiviral, and baculoviral vectors. We observed up to a 100-fold improvement in reporter gene expression in cultured neurons and 20-fold improvement in the rat brain in vivo. Moreover, the cell-type specificity of the two tested promoters was well preserved and restricted to neurons. Finally, the expression driven by the new lentiviral vectors with the p65-potentiated synapsin-1 promoter showed no signs of decline or cell damage 4 weeks after injection. This approach should be suitable for constructing powerful and stable gene expression systems based on weak cell-specific promoters in neuronal phenotypes.

Animals↗
PubMed2006

Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

AIMS/HYPOTHESIS: The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. MATERIALS AND METHODS: NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. RESULTS: Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. CONCLUSIONS/INTERPRETATION: The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.

Animals↗
PubMed2006

Placental and membrane aquaporin water channels: correlation with amniotic fluid volume and composition.

OBJECTIVES: To assess the role of aquaporins (AQPs) in the regulation of amniotic fluid (AF) volume, we determined AF volume and composition and placental and fetal membrane AQP expression throughout the second half of murine gestation. METHODS: Pregnant CD1 mice were sacrificed at e10-19 and AF volume and composition determined. Placenta and fetal membranes were screened for AQP gene expression. AQP gene expression was quantified by real-time RT PCR and protein location determined by immunohistochemistry. Changes in AF volume were correlated with AQP expression. RESULTS: Both membranes and placenta demonstrated expression of AQP1, -3, -8 and -9. Advancing gestation was associated with increased AF volume from e10 to e16, with a marked decrease in AF volume from e16 to e19. By immunohistochemistry, AQP1 was localized to placental vessels and AQP3 to trophoblast. AF volume was negatively correlated with fetal membrane AQP1 and placental AQP1 and AQP9 expression, and positively correlated with placental AQP3 expression. CONCLUSION: Changes in AQPs with advancing gestation, and their correlation with AF volume, suggest a role in mediating placental and membrane water flow and ultimately AF volume. AQP1 appears to regulate fetal membrane water flow, and AQP3 is a likely candidate for the regulation of placental water flow.

Amniotic Fluid↗
PubMed2006

Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells.

Antigen-presenting cells such as dendritic cells (DCs) play a critical role in inducing and regulating immune responses. One effective strategy for DC-based immunotherapy is to regulate maturation and function of DC. In this study, we apply single-walled carbon nanotubes (SWNTs) to carry small interfering RNA (siRNA) to reach, enter and genetically modify DCs in vivo. We prepared positively charged SWNTs (SWNTs+) using 1,6-diaminohexane which was demonstrated by transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy and atomic force microscope. The functionalized SWNTs+ could absorb siRNA to form complexes of siRNA with SWNTs. These siRNA:SWNT+ complexes were preferentially taken up by splenic CD11c+ DCs, CD11b+ cells and also Gr-1+CD11b+ cells comprising DCs, macrophages and other myeloid cells to silence the targeting gene. Suppressor of cytokine signaling 1 (SOCS1) restricts the ability of DCs to break self-tolerance and induce antitumor immunity. Infusion of SWNTs+ carrying SOCS1siRNA reduced SOCS1 expression and retarded the growth of established B16 tumor in mice, indicating the possibility of in vivo immunotherapeutics using SWNTs-based siRNA transfer system.

Animals↗
PubMed2006

Oncolytic adenovirus-mediated transfer of the antisense chk2 selectively inhibits tumor growth in vitro and in vivo.

Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such therapeutics remains a major challenge. To resolve this problem, we constructed M3, a novel recombinant adenovirus with a 27-bp deletion in E1A CR2 region by which to realize tumor-specific replication, and an 829-bp of antisense chk2 fragment inserted into the E3 coding region. In this design, M3 exploited the native adenovirus E3 promoters to express antisense chk2 cDNA in a viral replication-dependent fashion, and preferentially silenced the chk2 gene in tumor cells. In vitro and in vivo assays confirmed that downregulated chk2 expression induced by M3 infection was tumor-specific and virus replication-dependent. Furthermore, systemic administration of M3 combined with a low dose of cisplatin cured 75% (9/12) of orthotopic hepatic carcinoma mouse models that were otherwise resistant to cisplatin. Our results indicated that the upcoming development in this field would improve the antitumor efficacy and maximize the synergistic effect of oncolytic viruses administered with traditional chemotherapy or radiotherapy.

Adenoviridae↗
PubMed2006

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter.

Therapeutic gene expression in glial cells has been tested for the treatment of neurological diseases in animal models. Many of such studies used the promoter of the glial fibrillary acidic protein (GFAP) to restrict gene expression to astrocytes. We have investigated in the current study whether it is possible to improve the transcriptional activity of the cellular promoter, while maintaining its cell-type specificity. We constructed an expression cassette containing a hybrid cytomegalovirus (CMV) enhancer/GFAP promoter and placed it into baculovirus vectors, a type of viral vectors capable of transducing astrocytes. In another vector design, we used inverted terminal repeats (ITRs) from adeno-associated virus (AAV) to flank the expression cassette. The recombinant baculoviruses with the hybrid promoter improved gene expression levels over two orders of magnitude in glial cell lines and by 10-fold in the rat brain when compared to the baculoviruses with the GFAP promoter alone. The expression was further improved by ITR flanking, reaching levels higher than that mediated by the baculovirus vectors with the CMV immediate-early enhancer/promoter (CMV promoter). Using these recombinant baculoviruses, we observed extended in vivo transgene expression in the rat brain at 90 days postinjection, by which time the gene expression from baculovirus vectors with the GFAP or CMV promoter had already become undetectable. The astrocyte specificity of the GFAP promoter was preserved in the engineered expression cassette with the CMV enhancer and the AAV ITRs, as demonstrated by immunohistological analysis of brain samples and an axonal retrograde transport assay. Taken together, our findings suggest that these baculovirus vectors may serve as useful tools for astrocyte-specific gene expression in the brain.

Animals↗
PubMed2006

The challenge of real-time measurements of nitric oxide release in the brain.

Nitric oxide (NO) acts as a signalling molecule in the brain. NO has been implicated in a variety of central functions such as learning, plasticity and neurodegeneration. It is also involved in regulation of autonomic homeostasis at different levels of neuraxis including the nucleus tractus solitarii. In spite of the ample evidence for NO-mediated signalling many aspects of its mechanism of action the brain remain unknown largely due to the difficulties of NO detection in real time coupled with its unique ability to freely cross cellular membranes. Here we give a brief overview of the currently available options for NO detection in the brain (such as electrochemistry, fluorescent indicators, electron-paramagnetic resonance) and consider some of their limitations. We conclude that it would be extremely useful to develop a highly sensitive probe for NO detection with some kind of build-in amplification which would magnify the changes triggered by NO to allow its detection within microdomains of the brain tissue in real time.

Animals↗
PubMed2006

Glycocalyx-mimetic dextran-modified poly(vinyl amine) surfactant coating reduces platelet adhesion on medical-grade polycarbonate surface.

A dextran-modified poly(vinyl amine) comb-like surfactant polymer, poly(N-vinyl dextran aldonamide-co-N-vinyl hexanamide), that can surface-adsorb on hydrophobic polymeric substrates, was designed to improve the interfacial blood-compatibility of polymeric biomaterials. Medical-grade polycarbonate was selected as a model substrate because of its extensive use in blood-contacting biomedical devices like hemodialyzers, blood pumps and oxygenators. The surfactant polymer was physisorbed from aqueous solution onto the polycarbonate substrate. The surfactant coating was stable under dynamic shear conditions in whole blood, as confirmed by fluorescence microscopy and total internal reflection fluorescence (TIRF) experiments with fluorescein-labeled surfactant polymer. The coated disks and uncoated control disks were exposed to platelet-rich plasma (PRP) and whole human blood in a rotating disk system (RDS) to study platelet-adhesion under dynamic shear stress environments. Adhered platelets were stained with fluorescein isothiocyante (FITC)-tagged anti-CD41a monoclonal antibody and imaged by epifluorescence microscopy. Complimentary images were obtained by phase-contrast microscopy. Platelet adhesion on the surfactant-coated disks was reduced by approximately 90%, compared with uncoated disks. The images also showed a concomitant reduction in platelet-derived microparticles on surfactant-coated disks, compared with uncoated disks. The results suggest potential application of carbohydrate-modified surfactant polymers as a glycocalyx-mimetic non-thrombogenic interfacial coating for blood-contacting biomaterials.

Adult↗
PubMed2006

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis.

To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

Adenocarcinoma↗
PubMed2006

Unilateral low-frequency stimulation of central piriform cortex delays seizure development induced by amygdaloid kindling in rats.

Low-frequency stimulation of the kindling site interferes with the course of kindling epileptogenesis. The present study examined the effect of unilateral low-frequency stimulation of the central piriform cortex on seizure development induced by amygdaloid kindling in rats. The ipsilateral or contralateral central piriform cortex received low-frequency stimulation (15 min train of 0.1 ms pulses at 1 Hz and 50-150 muA) immediately after termination of once daily kindling stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 microA) in the right amygdala for 30 days. Low-frequency stimulation of either the ipsilateral or contralateral central piriform cortex significantly suppressed the progression of seizure stages and reduced afterdischarge duration throughout the course of amygdaloid kindling. The marked suppression induced by low-frequency stimulation of the central piriform cortex on either side was predominantly due to the significant retardation of progression from stage 0 to stage 1 and stage 3 to stage 4 seizures. In addition, the suppressive effect of low-frequency stimulation did not disappear when the stimulation was stopped; it could persist for at least 10 days. These findings indicate that brain areas other than the kindling focus, such as the central piriform cortex on both sides, can also be used as reasonable targets for low-frequency stimulation to retard seizure development induced by amygdaloid kindling. Secondly, like the ipsilateral central piriform cortex, the contralateral central piriform cortex may also participate in the progression and secondary generalization of focal seizures. The study suggests that unilateral low-frequency stimulation of the central piriform cortex may have a significant antiepileptogenic effect, and may be helpful for exploring effective and long-lasting therapies for human temporal lobe epilepsy.

Amygdala↗
PubMed2006

Elevated levels of inducible heat shock 70 proteins in human brain.

Differential expression of heat shock genes can modulate protein folding and stress-related cell death. There have been no comparisons of their levels of expression in animals and humans. Levels of expression of heat shock 70 genes in human brain were compared to levels in non-stressed and heat-stressed brain of rat. Levels of hsp70 proteins in human brain were 43-fold higher than in non-stressed rat brain and 14-fold higher than highest induced levels in brains of heat-shocked rats. Levels of constitutively synthesized hsc70 proteins were approximately 1.5-fold higher in human than in rat. Higher levels of hsp70 proteins in human brain may serve to protect brain cells against stress-related death or dysfunction throughout the lifespan.

Aged↗
PubMed2006

Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into the nervous system.

BACKGROUND: Polyethylenimines (PEIs) with high molecular weights are effective nonviral gene delivery vectors. However, the in vivo use of these PEIs can be hampered by their cellular toxicity. In the present study we developed and tested a new PEI polymer synthesized by linking less toxic, low molecular weight (MW) PEIs with a commonly used, biocompatible drug carrier, beta-cyclodextrin (CyD). METHODS AND RESULTS: The terminal CyD hydroxyl groups were activated by 1,1'-carbonyldiimidazole. Each activated CyD then linked two branched PEI molecules with MW of 600 Da to form a CyD-containing polymer with MW of 61 kDa, in which CyD served as a part of the backbone. The PEI-CyD polymer developed was soluble in water and biodegradable. In cell viability assays with sensitive neurons, the polymer performed similarly to low-MW PEIs and displayed much lower cellular cytotoxicity compared to PEI 25 kDa. The gene delivery efficiency of the polymer was comparable to, and at higher polymer/DNA ratios even higher than, that offered by PEI 25 kDa in neural cells. Attractively, intrathecal injection of plasmid DNA complexed by the polymer into the rat spinal cord provided levels of gene expression close to that offered by PEI 25 kDa. CONCLUSIONS: The polymer reported in the current study displayed improved biocompatibility over non-degradable PEI 25 kDa and mediated gene transfection in cultured neurons and in the central nervous system effectively. The new polymer would be worth exploring further as an in vivo delivery system of therapeutic genetic materials for gene therapy of neurological disorders.

Animals↗