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Nan Zhang

Publications and source records attributed to Nan Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.

1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.

Animals↗
PubMed2006

Sirolimus is associated with reduced islet engraftment and impaired beta-cell function.

Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a fraction of transplanted islets can survive and become engrafted, and yet the underlying mechanism remains unclear. In this study, we examined the effect of sirolimus, a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function. To distinguish the effect of sirolimus on immune rejection from its effect on islet engraftment, we used a syngeneic model. Diabetic mice were transplanted with 250 islets under the renal capsule, followed by treatment with sirolimus or vehicle for 14 days. Thirty days posttransplantation, islet grafts were retrieved for the determination of insulin content and vascular density. Compared with mock-treated controls, diabetic recipient mice receiving sirolimus exhibited impaired blood glucose profiles and reduced glucose-stimulated insulin secretion, correlating with reduced intragraft insulin content and decreased vascular density. Islets exposed to sirolimus for 24 h in culture displayed significantly diminished glucose-stimulated insulin release, coinciding with decreased pancreas duodenum homeobox-1 and GLUT2 expression in cultured islets. Furthermore, sirolimus-treated diabetic recipient mice, as opposed to mock-treated controls, were associated with dyslipidemia. These data suggest that sirolimus, administered in the early posttransplantation phase, is a confounding factor for reduced islet engraftment and impaired beta-cell function in transplants.

Animals↗
PubMed2006

CD4+ CD25+ regulatory T-cells inhibit the islet innate immune response and promote islet engraftment.

Early islet cell loss is a significant problem in clinical islet cell transplantation. Diverse stress stimuli induce innate immune responses in islets that contribute to beta-cell dysfunction, inflammation, and loss. Here, we show that cytokine-stimulated murine islets express multiple inflammatory chemokines that recruit T-cells and thereby impair islet function in vitro and in vivo. Both nonislet ductal and exocrine elements and the individual islet cellular components contribute to this innate immune response. CD4+ CD25+ regulatory T-cells inhibit islet chemokine expression through a cell contact-dependent, soluble factor-independent mechanism and inhibit effector T-cell migration to the islet. Regulatory T-cells can also migrate to stimulated islets. Cotransfer of regulatory T-cells with islets in a transplantation model prevents islet innate immune responses and inflammation and preserves normal architecture and engraftment. Regulatory T-cell inhibition of multiple components of innate immune responses may be a fundamental aspect of their function that influences ischemia-reperfusion injury and adaptive immunity.

Animals↗
PubMed2006

[Cell brain abnormalities in carcinogenesis].

Cancer seriously threatens the health of humans. The mechanism underlying the carcinogenesis, however, is unclear. Among all the related hypotheses, the lately postulated 'cell brain' theory, challenging the conventional theory that gene abnormalities are the major players in carcinogenesis, is catching more and more attentions. According to this theory, the complex composes of the centrosome, centrioles, and connecting microtubules, and acts as the commandeering center of a cell in the structures and functions, equals to the brains of human being and animals, centering all the cellular activities. As far as carcinogenesis is concerned, cancer was interpreted by this theory as a brain illness' rather than a genetic disease. This article, based on the latest findings, reevaluated the roles of the composing parts of cell brain, discussed their correlations to cancer development, and further explored the mechanisms of carcinogenesis including hepatocarcinogenesis. It will contribute not only to improving cancer diagnosis and prevention but also to the design of novel anticancer agents, particularly the centrosome/cell brain-targeting agents.

Animals↗
PubMed2005

Tetrazolium violet induces G0/G1 arrest and apoptosis in brain tumor cells.

Tetrazolium violet (TV), a potent anticancer agent, has been shown to induce cell growth-inhibition in tumor cells. However, the related mechanism has not been revealed yet. In this report we assessed the influence of TV on cell growth and cell cycle in brain tumor cells. Treatment of C6 tumor cells with TV (5-15 microM for 24-72 h) resulted in a growth inhibition in a dose and time-dependent manner and G0/G1 phase arrest, determined by flow cytometry analysis. These effects were accompanied by apoptosis other than necrosis, evidenced by nuclear condensation, terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay and trypan blue exclusion assay plus lactate dehydrogenase (LDH) release assay. Treatment of cells with TV at 15 microM for 24 h resulted in an increase in the activity of caspase-3, evidenced by colorimetric assay, and a dramatic up-regulation of p53, accompanied with a significant increase of Bax/Bcl-2 ratio, as evidenced by immunofluorescence assay. These results suggest that TV induces growth inhibition of C6 cells through p53-midiated apoptotic pathway and G0/G1 checkpoint mechanism. Although detailed mechanisms remain to be explored, selective blockage of tumor cells in G0/G1 phase accompanied by p53-associated apoptosis makes tetrazolium violet a promising anticancer agent, meriting further investigations.

Antineoplastic Agents↗
PubMed2005

[Therapeutic neovascularization with autologous bone marrow CD34+ cells transplantation in hindlimb ischemia].

OBJECTIVE: To explore whether transplantation of autologous bone marrow stem cells might augment angiogenesis and collateral vessel formation in a canine model of hindlimb ischemia. METHODS: CD34(+) stem cells were centrifugation through Ficoll and an immune magnetic cell sorting system from bone marrow (20 ml) of canine (n = 5) and induced into endothelial cells with VEGF in vitro, and expression of von Willebrand factor. Bilateral hindlimb ischemia was surgically induced in canines and Dil fluorescence labeled autologous stem cells were transplanted into the ischemic tissues. RESULTS: Four weeks after transplantation, fluorescence microscopy revealed that transplanted cells were incorporated into the capillary network among preserved skeletal myocytes. The stem cells transplanted group had more angiographically detectable collateral vessels, a higher capillary density (12.0 +/- 2.8 vs. 5.0 +/- 1.6 per field; t = 4.17 P < 0.05) and a higher ABI (0.58 +/- 0.14 vs. 0.32 +/- 0.11; t = 2.95, P < 0.05). CONCLUSIONS: Direct local transplantation of autologous bone marrow CD34(+) stem cells seems to be a useful strategy for therapeutic neovascularization in ischemic tissues in adults, consistent with "therapeutic vasculogenesis."

Animals↗
PubMed2005

Transduction of pancreatic islets with pseudotyped adeno-associated virus: effect of viral capsid and genome conversion.

BACKGROUND: Recombinant adeno-associated viral (rAAV) vectors currently show promise for islet gene therapy. In the presence of complementing AAV2 Rep proteins, AAV2 genomes can be packaged with other serotype capsids to assemble infectious virions. During transduction, the ssDNA to dsDNA conversion is one of the major rate-limiting steps that contribute to the slow onset of transgene expression. METHODS: Using pseudotyping strategy, we produced double-stranded (dsAAV) and single-stranded (ssAAV) rAAV2 genomes carrying the GFP reporter gene packaged into AAV1, AAV2, and AAV5 capsids. The ability of cross-packaged AAV1, AAV2, and AAV5 at the same genome containing particle (gcp) concentration to transduce murine and human pancreatic islets was evaluated by GFP positive cell percentage. Transgenic expression was also determined by transplant transduced human islet into SCID mice. RESULTS: Pseudotyped rAAV2/1 based vectors transduced murine islets at greater efficiency than either rAAV2/2 or rAAV2/5 vectors. For human islets transduction, the rAAV2/2 vector was more efficient than rAAV2/1 or rAAV2/5 vectors. rAAV2/2 transduced human islets more efficiently than murine islets, while rAAV2/1 transducted murine islets more efficiently than human islets. dsAAV, which do not require second strand synthesis and thus are potentially more efficient, evidenced 5 fold higher transduction ability than ssAAV vectors. Pseudotyped rAAV transduced islet grafts maintained normal function, expressed transgenic product persistently in vivo, and reversed diabetes. CONCLUSIONS: The transduction efficiency of rAAV vectors was dependent on the cross-packaged capsid. The vector capsids permit species-specific transduction. For human islets, dsAAV2/2 vectors may be the most efficient vector for clinical development.

Adenoviridae↗
PubMed2005

Generation of rituximab polymer may cause hyper-cross-linking-induced apoptosis in non-Hodgkin's lymphomas.

PURPOSE: Although Rituximab has produced significant tumor regressions in lymphoma patients, only 50% respond. Clinically, it has been shown that the major mechanism of action of Rituximab is antibody-dependent cytotoxicity requiring presentation by Fc-bearing cells. To improve the clinical efficacy of Rituximab for the treatment of CD20+ lymphomas, we now describe a new formulation of Rituximab, which, on direct binding to target, can induce apoptosis. METHODS: In this report, enhanced apoptosis was observed by treating CD20+ lymphoma cells with a new polymer formulation of Rituximab. The polymer was produced by formation of a peptide bond using the sugar moiety of dextran (MW 6,000) to generate a clinically relevant reagent for use in vivo. RESULTS: Comparison of Rituximab with a previously described dimer and the newly generated polymer shows that the polymer induced apoptosis more effectively in CD20+ cells as shown by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay (Rituximab, 3%; dimer, 3%; polymer, 58%). Consistent with these results, the polymer produced marked regression in CD20+ lymphoma xenografts, whereas the dimer and monomer reagents showed little effect. In addition, we were able to show that the level of apoptosis induced in human lymphoma cell lines was in accordance with the extent of both surface CD20 clustering and caspase-3 activation. CONCLUSIONS: These data suggest that hyper-cross-linking-induced apoptosis can be simulated by the use of a dextran polymer of Rituximab, which, when used in vivo, can directly kill CD20+ lymphoma cells and improve the clinical efficacy of this important therapeutic for human B-cell lymphomas.

Animals↗
PubMed2005

[Gamma knife radiosurgery for large trigeminal schwannomas].

OBJECTIVE: To evaluate the role of gamma knife (GK) radiosurgery in controlling large trigeminal schwannoma. METHODS: The clinical data of 30 patients suffering from large trigeminal schwannoma with a maximum diameter of 39.0 mm (31.0 to 53.0 mm), who underwent GK radiosurgery, used as the primary treatment modality in 20 patients and used to cure the residuals of tumor after microsurgery in 10 patients, with the maximum irradiation dose to tumor of 25.8 Gy (20.0 to 33.0 Gy) and a tumor margin dose of 12.2 Gy (9.0 to 14.0 Gy), were analyzed respectively. RESULTS: The 30 patients had been followed up for 78 months (24 to 136 months). Twenty-nine of the 30 patients were alive, and one patient with malignant trigeminal schwannoma died of tumor progression 36 months after the GK radiosurgery. Neurological deficits were improved in 24 patients and 3 patients' condition remained stable. Two patients' symptoms worsened 5 and 30 months after the GK radiosurgery respectively because of tumor swelling and tumor cyst enlarging. Then these two patients underwent microsurgery and their tumors were subtotally removed. Disappearance of tumor occurred in 4 patients, a marked decrease in tumor volume was observed in 20 patients, three tumors kept unchanged or slightly regressed in volume, and 3 tumors, including that of the patient who died, progressed. The tumor-growth control rate was 90% (27/30). Two patients underwent craniotomy after GK radiosurgery and one of these 2 resected specimens underwent histopathological examination. The histopathological findings of this tumor resected 30 months after GK radiosurgery revealed that most of the tumor tissue necrosed and was full of microcysts, the residual tumor cells in peripheral areas underwent hyaline degeneration, and the nuclei showed pyknosis. CONCLUSION: GK may be a good alternative treatment for selective patients suffering from large trigeminal schwannoma with a maximum diameter <or= 40 mm.

Adult↗
PubMed2005

Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents: parallel synthesis for lead optimization of amide region.

A novel series of p21 chemoselective agents containing a pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides were identified by high throughput screening. Optimization of the amide region by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described. The isopropyl carbamate derivative 34 was identified as a highly chemoselective agent displaying a potency of 51 nM in the p21 deficient cell line.

Amides↗
PubMed2005

The nitric oxide-cGMP signaling pathway differentially regulates presynaptic structural plasticity in cone and rod cells.

Although abundant structural plasticity in the form of axonal retraction, neurite extension, and formation of presynaptic varicosities is displayed by photoreceptors after retinal detachment and during genetic and age-related retinal degeneration, the mechanisms involved are mostly unknown. We demonstrated recently that Ca(2+) influx through cGMP-gated channels in cones and voltage-gated L-type channels in rods is required for neurite extension in vitro (Zhang and Townes-Anderson, 2002). Here, we report that the nitric oxide (NO)-cGMP signaling pathway is active in photoreceptors and that its manipulation differentially regulates the structural plasticity of cone and rod cells. The NO receptor soluble guanylyl cyclase (sGC) was detected immunocytochemically in both cone and rod cells. Stimulation of sGC increased cGMP production in retinal cultures. In cone cells, quantitative analysis showed that NO or cGMP stimulated neuritic sprouting; this stimulatory effect was dependent on both Ca2+ influx through cGMP-gated channels and phosphorylation by protein kinase G (PKG). At the highest levels of cGMP, however, cone outgrowth was no longer increased. In rod photoreceptors, NO or cGMP consistently inhibited neuritic growth in a dose-dependent manner; this inhibitory effect required PKG. When NO-cGMP signaling was inhibited, changes in the neuritic development of cone and rod cells were also observed but in the opposite direction. These results expand the role of cGMP in axonal activity to adult neuritogenesis and suggest an explanation for the neurite sprouting observed in an autosomal recessive form of retinitis pigmentosa that is characterized by high cGMP levels in photoreceptor layers.

Ambystoma↗
PubMed2005

Clinical comparison of ibutilide and propafenone for converting atrial flutter.

OBJECTIVE: To evaluate the efficacy and safety of intravenous ibutilide and propafenone for immediate treatment of atrial flutter. METHODS: Forty patients with atrial flutter with an arrhythmia duration of three hours to 90 days were randomized to receive up to two 10-minute infusions of ibutilide (1 and 1 mg) or propafenone (70 and 70 mg) with a 10-minute interval. RESULTS: Ibutilide was superior to propafenone for treating atrial flutter (90% vs. 30%, p < 0.01). The median conversion time in the ibutilide group was 11 min (the 25th and 75th percentile was 10 and 45 min), and the median conversion time in the propafenone group was 35 min (range 20-55 min). In all patients, the duration of arrhythmia before treatment was a predictor of arrhythmia termination, although this was more obvious in the group that received ibutilide. Conversion of atrial flutter by ibutilide was characterized mainly by increased cycle length variability. Bradycardia (2/20) and hypotension (4/20) were more common side effects with propafenone. Of 20 patients given ibutilide, 8 (40%) who developed monomorphic ventricular extrasystoles or repetitive atrial flutter with aberrant conduction tachycardia, no one required any specific treatment except for the interruption of ibutilide infusion. CONCLUSION: Ibutilide is highly effective for rapidly terminating atrial flutter. This new class III drug, under monitored conditions, is a potential alternative to currently available cardioversion options.

Adult↗
PubMed2005

Does the cell-brain theory work in explaining carcinogenesis?

As a major microtubule-organizing center, the centrosome, together with the embedded centrioles and connecting filaments (or microtubules), has lately been proposed to be the "brain" of a cell. Although there are a lot of works to be done to test this hypothesis, emerging data have suggested that this centrosome-centered "cell brain" is playing increasingly important roles in cell control. Genes seem not to tell the whole story, despite the commonly held view that genetic alteration is the cause of most medical problems including cancer development. Although the mechanisms through which gene expression and protein synthesis are regulated remain to be studied, current advances in our understanding of the roles of the centrosome in the regulation of DNA synthesis, DNA repair, cell cycle, apoptosis and in the maintenance of genetic stability are challenging our tradition thoughts. Genetic alterations may be repaired by the centrosome-centered "cell brain"-mediated self-defense, but the cell brain defects intend to cause genetic alterations, which, in turn, may result in cancer development. Further understanding of the roles of the centrosome/cell brain in these and other new aspects are becoming very helpful in comprehending why and how medical problems including tumors develop. Meanwhile, it suggests that great attention should be given to the centrosome/cell brain, instead of gene alone when treating medical problems, which is discussed in this paper on the basis of cell brain theory and may prove helpful in shedding light on the often paradoxical observations seen in cell control, particularly in cancer development.

Apoptosis↗
PubMed2005

Long-term results of Leksell gamma knife surgery for trigeminal schwannomas.

OBJECT: The authors evaluated the long-term efficacy of gamma knife surgery (GKS) in patients with trigeminal schwannomas. METHODS: Fifty-six patients, 31 women and 25 men (mean age 42 years), underwent GKS for trigeminal schwannomas. Fourteen had previously undergone surgery, and GKS was the primary treatment in the remaining 42 patients. The mean target volume was 8.7 cm3 (range 0.8-33 cm3); the mean maximum dose was 27 Gy (range 20-40 Gy); the mean tumor margin dose was 13.3 Gy (range 10-15 Gy); and the mean follow-up period was 68 months (range 27-114 months). Disappearance of the tumor occurred in seven patients. An obvious decrease in tumor volume was observed in 41 patients, four tumors remained unchanged, and four tumors progressed at 5, 26, 30, and 60 months, respectively. One patient with disease progression died of tumor progression at 36 months after GKS. The tumor growth control rate in this group was 93% (52 of 56 cases). Mild numbness or diplopia was relieved completely in 14 patients. Improvement of other neurological deficits was demonstrated in 25 patients. Trigeminal nerve dysfunction was either unchanged or slightly worse in 13 patients after GKS. Four patients experienced mild symptom deterioration related to tumor progression. CONCLUSIONS: Radiosurgery proved to be an effective treatment for small- and medium-sized trigeminal schwannomas. Some larger tumors are also suitable for radiosurgery if there is no significant brainstem compression.

Abducens Nerve Diseases↗
PubMed2005

The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain.

OBJECT: The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. METHODS: Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel-Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5-55 mm). The mean follow up after GKS was 66 months (range 24-114 months). The mean prescription dose was 17.2 Gy (range 12-24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. CONCLUSIONS: Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.

Adolescent↗
PubMed2005

[The study on identification of lidocaine in blood and CSF by GC/MS].

OBJECTIVE: To establish a rapid and simple gas chromatographic-mass spectric method for qualitative and quantitative analysis of lidocaine in blood and cerebrospinal fluid(CSF). METHODS: Following an acidification of HCl, blood or CSF was alkalinized with NaOH (pH=9) and extracted with ether for two times. Evaporated in a water bath and with an air velocity of nitrogen gas, extract was dissolved with ethanol and analyzed by a gas chromatographic-mass spectrum method, lidocaine was analyzed qualitatively and quantitatively by GC/MS (SIM:86, 58, 72, 87). RESULTS: Linear range of lidocaine detected in blood or CSF by this method is 1.0-60.0 microg x mL(-1) (r=0.9999), the minimum detected concentration of lidocaine was 0.02 microg x mL(-1) (S/N=3), recovery is at 85%-103%. This method was used in the determination of lidocaine in dog model died of the anesthesia with lidocaine. CONCLUSION: This study provided a gas chromatographic-mass spectric analysis for lidocaine in blood and CSF. This method was more selective, little interferefering, more sensitivities and simpler. It could be used in the detection of lidocaine in biological fluids.

Anesthesia, Epidural↗
PubMed2005

[Analysis of prognostic factors of and to establish a predictive model for patients with chronic severe hepatitis].

OBJECTIVE: To analyze prognostic factors of and to develop a prognostic model for patients with chronic severe hepatitis (CSH). METHODS: From December 1998 to October 2003, 385 in-patients being treated for chronic severe hepatitis were evaluated. The main clinical and laboratory variables were analyzed as predictive factors of survival with Cox univariate and multivariate regression models. RESULTS: The median survival time of this study group was 47 days. The survival rates at 1, 3, 6 months, 1-year, and 3 years were 66.2%, 32.9%, 26.9%, 22.9% and 17.7% respectively. Four prognostic factors were extracted using Cox's proportional hazard model; the prognostic index (PI) was calculated using the following formula consisting of these factors. PI = 0.016loge + 1.148 hepatic encephalopathy + 0.294loge (bilirubin micromol/L) - 0.826loge (prothrombin time activity). The model accurately predicted 3 months survival in an independent series of 84 patients with chronic severe hepatitis. CONCLUSION: The developed model is valuable in prognostic evaluation of chronic severe hepatitis and it may be useful to guide clinicians in selecting treatment methods for CSH.

Adolescent↗