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1.
Heliyon ; 10(12): e32490, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38994096

ABSTRACT

Purpose: To investigate the factors influencing hypothermia during pancreaticoduodenectomy and establish and verify a prediction model. Method: The clinical data of patients undergoing pancreaticoduodenectomy in Hunan People's Hospital between January 1, 2022 and October 15, 2022 were analysed. The patients were divided into a hypothermia group (n = 302) and a non-hypothermia group (n = 164) according to whether hypothermia occurred during surgery. A binary logistic regression model was used to analyse the independent risk factors for hypothermia in patients undergoing pancreaticoduodenectomy. A risk prediction model was established, and R software was used to plot a column graph. The predictive value of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: Among the 466 patients undergoing pancreaticoduodenectomy, 302 (64.81 %) had hypothermia, including 154 men and 148 women, with a median age of 58.6 (38-86) years. The binary logistic regression analysis showed that low body mass index (BMI), room temperature at the time of entry, intraoperative flushing fluid volume and peritoneal flushing fluid temperature were independent risk factors for intraoperative hypothermia in patients undergoing pancreaticoduodenal surgery (P < 0.05). A multivariate logistic regression analysis (backward logistic regression) was used to establish the prediction model. The area under the ROC curve was 0.927, P ≤ 0.001, the sensitivity was 0.921 and the specificity was 0.848, indicating good differentiation by the prediction model. Conclusion: The nomogram constructed using four independent risk factors: BMI, room temperature at the time of entry, intraoperative peritoneal flushing fluid volume and intraoperative peritoneal flushing fluid temperature, has good predictive efficacy and good clinical application value for predicting intraoperative hypothermia in patients undergoing pancreaticoduodenectomy.

2.
Bioorg Med Chem Lett ; 26(11): 2680-4, 2016 06 01.
Article in English | MEDLINE | ID: mdl-27106712

ABSTRACT

Rutin exists in medicinal herbs, fruits, vegetables, and a number of plant-derived sources. Dietary sources containing rutin are considered beneficial because of their potential protective roles in multiple diseases related to oxidative stresses. In the present study, the change and antioxidation activity of rutin in Maillard reaction with lysine through a heating process were investigated. There is release of glucose and rhamnose that interact with lysine to give Maillard reaction products (MRPs), while rutin is converted to less-polar quercetin and a small quantity of isoquercitrin. Because of their high cell-membrane permeability, the rutin-lysine MRPs increase the free radical-scavenging activity in HepG2 cells, showing cellular antioxidant activity against Cu(2+)-induced oxidative stress higher than that of rutin. Furthermore, the MRPs significantly increased the Cu/Zn SOD (superoxide dismutase) activity and Cu/Zn SOD gene expression of HepG2 cells, consequently enhancing antioxidation activity.


Subject(s)
Antioxidants/pharmacology , Lysine/pharmacology , Rutin/pharmacology , Antioxidants/chemistry , Cell Membrane Permeability/drug effects , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Lysine/chemistry , Maillard Reaction , Molecular Structure , Oxidative Stress/drug effects , Rutin/chemistry , Structure-Activity Relationship , Superoxide Dismutase/metabolism
3.
J Chem Phys ; 144(5): 054305, 2016 Feb 07.
Article in English | MEDLINE | ID: mdl-26851919

ABSTRACT

Time-resolved pump-probe photoelectron spectroscopy has been used to study the relaxation dynamics of gaseous [Pt2(µ-P2O5H2)4 + 2H](2-) after population of its first singlet excited state by 388 nm femtosecond laser irradiation. In contrast to the fluorescence and phosphorescence observed in condensed phase, a significant fraction of the photoexcited isolated dianions decays by electron loss to form the corresponding monoanions. Our transient photoelectron data reveal an ultrafast decay of the initially excited singlet (1)A2u state and concomitant rise in population of the triplet (3)A2u state, via sub-picosecond intersystem crossing (ISC). We find that both of the electronically excited states are metastably bound behind a repulsive Coulomb barrier and can decay via delayed autodetachment to yield electrons with characteristic kinetic energies. While excited state tunneling detachment (ESETD) from the singlet (1)A2u state takes only a few picoseconds, ESETD from the triplet (3)A2u state is much slower and proceeds on a time scale of hundreds of nanoseconds. The ISC rate in the gas phase is significantly higher than in solution, which can be rationalized in terms of changes to the energy dissipation mechanism in the absence of solvent molecules. [Pt2(µ-P2O5H2)4 + 2H](2-) is the first example of a photoexcited multianion for which ESETD has been observed following ISC.

4.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(4): 2695-7, 2016 07.
Article in English | MEDLINE | ID: mdl-26477619

ABSTRACT

In this study, the complete mitochondrial genome of Ochetobius elongatus was first sequenced and annotated. The entire mitogenome is 16 613 bp in length and has a typical vertebrate mitochondrial genetic trait, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and a control region. The overall nucleotide composition of O. elongatus mt genome is A: 30.96%, T: 25.38%, G: 16.26% and C: 27.40%, with the A + T content of 56.34%, showing an obvious anti-G bias. Phylogenetic analyses suggest that Leuciscinae formed a clade first and then clustered with Cultrinae. The complete mitochondrial genome of O. elongatus will benefit to a better understanding of population genetics, molecular systematics and stock evaluation, further serving the germplasm resources conservation and management of O. elongatus.


Subject(s)
Cyprinidae/genetics , Genome, Mitochondrial/genetics , Animals , Base Composition/genetics , Cyprinidae/classification , DNA, Mitochondrial/genetics , Phylogeny , RNA, Ribosomal/genetics , RNA, Transfer/genetics , Sequence Analysis, DNA
5.
Infect Dis Poverty ; 4: 59, 2015 Dec 23.
Article in English | MEDLINE | ID: mdl-26699285

ABSTRACT

Substantial progress has been made in China in using traditional Chinese medicine (TCM) to treat acquired immune deficiency syndrome (AIDS). Our objective was to review the latest developments in TCM treatment of AIDS in China between 2004 and 2014. We reviewed the content of original articles investigating the efficacy and safety of TCM for treating AIDS published in Chinese and English language journals. Relevant references from 2004 to 2014 were found using PubMed and the China National Knowledge Infrastructure Database. We found that TCM has been widely used for treating AIDS and its complications in China. The number of TCM studies has increased, which indicates efficacy and safety. Measures of efficacy in the reviewed articles included the alleviation of human immunodeficiency virus (HIV)-related signs and symptoms, improvements in quality of life, improvements in long-term survival, counteraction of the adverse side effects of antiviral drugs, promotion of immune reconstitution, and improvement of laboratory results. In sum, the literature indicates that TCM is safe. TCM plays an important role in the treatment of AIDS. Some studies have attempted to measure the efficacy and safety of TCM for treating AIDS, but more evidence is needed. Therefore, more research on this topic is required in the future.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Acquired Immunodeficiency Syndrome/history , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/mortality , Acquired Immunodeficiency Syndrome/virology , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , History, 21st Century , Humans , Immunomodulation/drug effects , Medicine, Chinese Traditional/adverse effects , Medicine, Chinese Traditional/history , Medicine, Chinese Traditional/methods , Quality of Life , Treatment Outcome , Viral Load
6.
Chin J Integr Med ; 21(4): 243-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25877652

ABSTRACT

Henan Province in China has a major epidemic of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Chinese medicine (CM) has been used throughout the last decade, and a management modality was developed, which can be described by unified-planning, graded-administration, and centralized-controlling (UGC). The UGC modality has one primary concept (patient-centered medicine from CM theory), four basic foundations (classifying administrative region, characteristics of CM on disease treatment, health resource conditions, and distribution of patients living with HIV), six important relationships (the "three uniformities and three combinations," and the six relationships therein guide the treatment of AIDS with CM), and four key sections (management, operation, records, and evaluation). In this article, the authors introduce the UGC modality, which could be beneficial to developing countries or resource-limited areas for the management of chronic infectious disease.


Subject(s)
Acquired Immunodeficiency Syndrome/therapy , Delivery of Health Care/organization & administration , Health Planning Organizations/organization & administration , Medicine, Chinese Traditional , China , HIV Infections/therapy , HIV-1 , Health Plan Implementation/organization & administration , Health Planning/organization & administration , Health Planning Organizations/standards , Humans , Medicine, Chinese Traditional/standards
8.
FEBS Lett ; 587(16): 2517-22, 2013 Aug 19.
Article in English | MEDLINE | ID: mdl-23850889

ABSTRACT

To investigate the autolysis pattern and activation of metacaspase in higher plants, the biochemical characteristics of purified recombinant type II metacaspase (LeMCA1) from tomato were explored. Western blotting analysis indicated that four cleaved bands were formed; two N-terminal fragments and two C-terminal fragments. N-terminal sequencing confirmed that LeMCA1 cleaves at Lys223 and Arg332. Site mutants indicated that catalytic Cys139, cleaved Lys223, Arg332 and predicted calcium binding Asp116/Asp117 are the key residues that are responsible for its Ca²âº and pH dependent activation. The cleavage of the full-size fragment seemed crucial for the activation of LeMCA1 in vitro.


Subject(s)
Caspases/chemistry , Plant Proteins/chemistry , Solanum lycopersicum/enzymology , Calcium/chemistry , Caspases/genetics , Enzyme Activation , Solanum lycopersicum/genetics , Models, Molecular , Mutagenesis, Site-Directed , Peptides/chemistry , Plant Proteins/genetics , Protein Structure, Tertiary , Recombinant Proteins/chemistry
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(3): 659-62, 2013 Mar.
Article in Chinese | MEDLINE | ID: mdl-23705427

ABSTRACT

The inner filter effect (IFE) and the absorption depth from the fluorescence material will directly lead to an artifact for intensity and spectral shape of the fluorescence spectra, and they restrict the application of fluorescence analysis. A two-component mixed solution with overlapping absorption spectra was used to develop a new method based on physical absorption model to correct the influences of IFE and the absorption depth on fluorescence intensity. The spectral investigations of terthiophene/ quinquethiophene mixture solution show that a good correction result can be obtained by using the above correction method, and the error after correction is less than 5 %.

10.
Phys Chem Chem Phys ; 15(18): 6726-36, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23549163

ABSTRACT

Photoelectron spectra of isolated [M-BDSZ](3-) (BDSZ = bisdisulizole, M = H, Li, Na, K, Cs) triply charged anions exhibit a dominant constant electron kinetic energy (KE) detachment feature, independent of detachment wavelengths over a wide UV range. Photoelectron imaging spectroscopy shows that this constant KE feature displays an angular distribution consistent with delayed rather than direct electron emission. Time-resolved pump-probe (388 nm/775 nm) two-colour photoelectron spectroscopy reveals that the constant KE feature results from two simultaneously populated excited states, which decay at different rates. The faster of the two rates is essentially the same for all the [M-BDSZ](3-) species, regardless of M. The slower process is associated with lifetimes ranging from several picoseconds to tens of picoseconds. The lighter the alkali cation is, the longer the lifetime of this state. Quantum chemical calculations indicate that the two decaying states are in fact the two lowest singlet excited states of the trianions. Each of the two corresponding photoexcitations is associated with significant charge transfer. However, electron density is transferred from different ends of the roughly chain-like molecule to its aromatic center. The energy (and therefore the decay rate) of the longer-lived excited state is found to be influenced by polarization effects due to the proximal alkali cation complexed to that end of the molecule. Systematic M-dependent geometry changes, mainly due to the size of the alkali cation, lead to M-dependent shifts in transition energies. At the constant pump wavelength this leads to different amounts of vibrational energy in the respective excited state, contributing to the variations in decay rates. The current experiments and calculations confirm excited state electron tunneling detachment (ESETD) to be the mechanism responsible for the observed constant KE feature. The ESETD phenomenon may be quite common for isolated multiply charged anions, which are strong fluorophores in the condensed phase - making ESETD useful for studies of the transient response of such species after electronic excitation.

11.
Neurol Sci ; 32(3): 433-41, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21409508

ABSTRACT

In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after injury to evaluate the time window. Neurological deficits, infarct volume, neural cell apoptosis and expressions of caspase-3 and Bcl-2 were measured. Compared to saline-treated control, NGF treatment at 2, 3 and 5 h after MCAO significantly reduced infarct volume, neural cell apoptosis and expression of caspase-3 (P < 0.01), up-regulated the expression of Bcl-2 and improved functional recovery (P < 0.01). However, treatment at latter time points did not produce significant neuroprotection. Neuroprotection treatment with NGF provides an extended time window of up to 5 h after ischemia/reperfusion brain injury, in part by attenuating the apoptosis.


Subject(s)
Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Nerve Growth Factor/administration & dosage , Neuroprotective Agents/administration & dosage , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Animals , Brain Ischemia/pathology , Disease Models, Animal , Drug Administration Schedule , Injections, Intraventricular , Male , Nerve Growth Factor/physiology , Neuroprotective Agents/pharmacology , Rabbits , Reperfusion Injury/pathology , Time Factors
12.
J Invest Surg ; 23(3): 149-55, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20590386

ABSTRACT

We evaluated the effects of intranasal vascular endothelial growth factor VEGF on neurological function and angiogenesis in ischemic boundary following cerebral ischemia. Sprague-Dawley rats were randomized into sham operation group (n = 9), VEGF group (n = 18), and control group (n = 18). The VEGF and control rats were intranasally administered (IN) with VEGF or saline, starting three days after middle cerebral artery occlusion (MCAO) and daily. Neurological scores were obtained at 1, 7, and 14 days after MCAO. Rats were sacrificed at 14 days, the von Willebrand factor (vWF) immunoreactive, BrdU(+)/vWF(+) cells, and microvessels were evaluated respectively. Compared to the control rats, intranasal administration of VEGF improved behavioral recovery, and increased the number of vWF(+), BrdU(+)/vWF(+) cells, and FITC-dextran perfused microvessels in ischemic boundary (p < .01). Our data suggest that intranasal administration of VEGF may induce angiogenesis in ischemic boundary and improve behavioral recovery following cerebral ischemia in rats, which may provide a powerful strategy for stroke.


Subject(s)
Neovascularization, Physiologic/drug effects , Recovery of Function/drug effects , Stroke/drug therapy , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor A/therapeutic use , Administration, Intranasal , Animals , Behavior, Animal/physiology , Brain Ischemia/drug therapy , Brain Ischemia/physiopathology , Male , Microvessels/physiology , Models, Animal , Rats , Rats, Sprague-Dawley , Stroke/physiopathology , Vascular Endothelial Growth Factor A/administration & dosage
13.
J Chem Phys ; 130(23): 234306, 2009 Jun 21.
Article in English | MEDLINE | ID: mdl-19548726

ABSTRACT

We have used femtosecond time-resolved photoelectron spectroscopy to examine the photodissociation dynamics of doubly charged anions IrBr(6)(2-) after excitation at h nu(pump) = 1.6 eV and with a detachment photon energy of h nu(probe) = 4.8 eV. Excited state dynamics proceed by successive decay of the initially excited state, by way of an intermediate and back to the electronic ground state. This is associated with lifetimes of tau(1) = 2.1+/-0.3 ps and tau(2) = 21+/-2 ps, respectively. After nonadiabatic relaxation, the internal energy of the dianion is sufficiently large to induce fragmentation and delayed emission of Br(-) over the repulsive Coulomb barrier with a 79+/-21 ps time constant. As both fragments are negatively charged, Coulomb repulsion at early times (and correspondingly small separations) is reflected in the transient photoelectron spectra. Analysis of both shifts and intensities of the time-dependent bromide detachment features allows determination of the shape of the dissociation barrier. A lower limit of the outer height was retrieved from the kinetic energy release of KER > or = 1.6 eV. Modeling of the dissociation rate with statistical rate theory results in an inner barrier height of E(RCB) = 0.95 eV.

14.
Neurosci Lett ; 461(3): 212-6, 2009 Sep 25.
Article in English | MEDLINE | ID: mdl-19559076

ABSTRACT

The aim of the present study was to assess the dose-effectiveness of intranasal (IN) vascular endothelial growth factor (VEGF)in the treatment of experimental stroke. Sprague-Dawley rats were randomized into four groups as IN low (100 microg/ml), IN middle (200 microg/ml) and IN high (500 microg/ml) VEGF-treated group, and IN saline-treated group (n=12), given recombinant human VEGF 165 or saline intranasally. Focal cerebral ischemia was induced by transient (90 min) middle cerebral artery occlusion (MCAO) method. Behavioral neurological deficits were assessed 1, 7 and 14 d after the onset of MCAO. Rats were sacrificed at 14 d, the brain sections were stained and an image analysis system was used to calculate the infarct volume. Microvessels were labeled by FITC-dextran and the segment lengths, diameters and number of microvessels were measured by Image Pro-Plus Version 6.0 software. Fourteen days post MCAO, infarct volume significantly reduced (P<0.01) in rats which received the middle dose of IN VEGF when compared to IN saline. And middle dose of VEGF significantly improved behavioral recovery (P<0.01). No significant difference in the behavioral recovery and infarct volume was observed between the saline-treated group and the low or high VEGF-treated groups (P>0.05). Compared to IN saline, middle and high doses of VEGF significantly increased the segment length, diameter and number of microvessels (P<0.01). No significant difference in the segment length, diameter and number of microvessels was observed between the IN saline-treated group and the low VEGF-treated group (P>0.05). The middle dose of IN VEGF was most effective on reducing infarct volume, improving behavioral recovery and enhancing angiogenesis in stroke brain, which can be used in the following treatments to further evaluate the effect of VEGF.


Subject(s)
Brain Ischemia/drug therapy , Stroke/drug therapy , Vascular Endothelial Growth Factor A/therapeutic use , Administration, Intranasal , Animals , Behavior, Animal/drug effects , Brain/blood supply , Brain/drug effects , Brain/pathology , Brain Ischemia/complications , Brain Ischemia/pathology , Dose-Response Relationship, Drug , Humans , Infarction, Middle Cerebral Artery/complications , Male , Microvessels/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , Stroke/etiology , Stroke/pathology , Vascular Endothelial Growth Factor A/administration & dosage
15.
Neurol Sci ; 30(3): 227-32, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19387543

ABSTRACT

Caspase-12 has been localized to endoplasmic reticulum (ER) and showed to involve ER stress-induced apoptosis. In the present work we investigated the temporospatial alterations of caspase-12 immunoreactivity in the penumbra following cerebral ischemia/reperfusion in rabbit. Transient cerebral ischemia was produced by intraluminal occlusion of the middle cerebral artery for 2 h followed by 1 h, 6 h, 1 day, 3 days, 7 days and 14 days of reperfusion. Caspase-12 immunohistochemistry was first increased in the penumbra 1 h after reperfusion, with a peak at day 1 to day 3, and then gradually decreased to basal level at day 14. The number of TUNEL-positive cells and ultrastructural observation of brain sections in the penumbra showed a similar change at the same time points. ER mediated by caspase-12 participated in apoptosis induced by cerebral ischemia/reperfusion injury, which may provide a new area for therapeutic intervention to ameliorate outcomes following cerebral ischemia.


Subject(s)
Apoptosis/physiology , Caspase 12/metabolism , Cerebrum/enzymology , Endoplasmic Reticulum/enzymology , Reperfusion Injury/enzymology , Animals , Cerebrum/pathology , Cerebrum/ultrastructure , Follow-Up Studies , Immunohistochemistry , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/enzymology , Infarction, Middle Cerebral Artery/pathology , Male , Rabbits , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Time Factors
16.
Neurol Res ; 31(10): 1092-6, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19309539

ABSTRACT

OBJECTIVE: Occluding the middle cerebral artery of small animals with an intraluminal filament to build a stroke model has gained increasing acceptance. In light of the growing demand for magnetic resonance imaging (MRI) studies using the clinical MRI scanner, large animal models can be superior to small animal models. In this work, we developed a modified rabbit model of stroke, which was assessed using clinical MRI scanner and compared with a most commonly silicone-coated filament model. METHODS: We presented a focal cerebral ischemia in rabbits. The key feature of this modified method is the use of a guide wire as a 'nylon suture'. At 3 days after ischemia, the percentage of brain infarct volume, neurobehavioral score, intracranial hemorrhagic incidence and dynamic changes of T(2) and apparent diffusion coefficient values were assessed respectively and compared between the focal cerebral models. RESULTS: Wire-induced models had more severe brain infarct size with less dispersion (32.7 +/- 6.5%, coefficient of variation=0.20) than that with filament models (25.4 +/- 8.9%, coefficient of variation=0.31; p<0.05). There were more significant MRI changes in the early stage, higher rate of technique success (wire, 20/20; filament, 17/20) and less intracranial hemorrhage (wire, 0/20; filament, 3/20) in wire-induced models than in filament-induced rabbits (p<0.05). CONCLUSION: Our data suggest that wire-induced method can provide a useful tool for the earlier research of ischemia.


Subject(s)
Brain/pathology , Infarction, Middle Cerebral Artery/pathology , Stroke/pathology , Analysis of Variance , Animals , Brain/physiopathology , Disease Models, Animal , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/physiopathology , Magnetic Resonance Imaging , Rabbits , Stroke/etiology , Stroke/physiopathology
17.
J Invest Surg ; 22(1): 29-34, 2009.
Article in English | MEDLINE | ID: mdl-19191155

ABSTRACT

Researchers suggest that endoplasmic reticulum (ER) stress cause apoptosis after ischemia. Caspase-12 has been localized to the ER and is a signal for apoptosis. We sought to clarify the role of caspase-12 in the vascular endothelial growth factor (VEGF) induced neuroprotective effect. Transient focal cerebral ischemia was produced by occluding left middle cerebral artery in rabbit. The expressions of caspase-12 and caspase-3 were detected by immunohistochemistry. Neuronal apoptosis was detected by TUNEL staining. We confirmed that the number of apoptotic cells and the expressions of caspase-12 and caspase-3 significantly increased during reperfusion. VEGF inhibited the cell apoptosis and the expressions of caspase-12 and caspase-3. These results suggest that VEGF may protect neurons from apoptosis by inhibiting ER stress pathway.


Subject(s)
Apoptosis , Caspase 12/metabolism , Endoplasmic Reticulum/metabolism , Infarction, Middle Cerebral Artery/metabolism , Vascular Endothelial Growth Factor A/metabolism , Animals , Caspase 3/metabolism , Cerebrum/pathology , Flow Cytometry , In Situ Nick-End Labeling , Infarction, Middle Cerebral Artery/pathology , Male , Rabbits , Reperfusion , Reperfusion Injury/pathology , Stress, Physiological
18.
Neurosci Lett ; 449(2): 108-11, 2009 Jan 09.
Article in English | MEDLINE | ID: mdl-18996442

ABSTRACT

The aim of the present study was to assess the potential of delivering VEGF directly into the central nervous system (CNS) following intranasal administration. Adult Sprague-Dawley rats were randomized into two groups, given [(125)I]-VEGF intranasally or intravenously. VEGF was intranasally administered in both nares alternately, the single dose is 10 microl with time interval of 2 min for about 18.5 min. The intravenous (IV) group was treated with 100 microl [(125)I]-VEGF intravenously. Thirty minutes after administration, rats were killed following blood sample collections, then the brains were removed, and olfactory bulb, striatum corpora, cortex, thalamus, pons, cerebella, medulla, hippocampus, cervical cord and other tissues were collected, weighted, under auto gamma counting and autoradiography analysis. Cisternal sampling of cerebrospinal fluid (CSF) was performed in an additional group of animals. Both gamma counting and high resolution phosphor imaging of tissue sections showed that intranasal administration of [(125)I]-VEGF resulted in substantial delivery throughout the CNS. The highest CNS tissue concentration following IN delivery was found in the trigeminal nerve, followed by the optic nerve, olfactory bulbs, olfactory tubercle, striatum, medulla, frontal cortex, midbrain, pons, appendix cerebri, thalamus, hippocampus, cerebellum. Intranasal administration of [(125)I]-VEGF also targeted the deep cervical lymph nodes. CSF did not contain [(125)I]-VEGF following intranasal administration. Intravenous [(125)I]-VEGF resulted in blood and peripheral tissue exposure higher concentrations than that intranasal administration, but CNS concentrations were significantly lower. The results suggest intranasally delivered VEGF can bypass the blood-brain barrier via olfactory- and trigeminal-associated extracellular pathways to directly entry into the CNS. Intranasal administration of VEGF may provide an effective way for the treatments of CNS diseases.


Subject(s)
Brain/metabolism , Vascular Endothelial Growth Factor A/administration & dosage , Vascular Endothelial Growth Factor A/pharmacokinetics , Administration, Intranasal , Afferent Pathways/anatomy & histology , Afferent Pathways/drug effects , Afferent Pathways/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Brain/anatomy & histology , Brain/drug effects , Iodine Radioisotopes/pharmacokinetics , Nasal Cavity/drug effects , Nasal Cavity/innervation , Nasal Cavity/metabolism , Olfactory Nerve/anatomy & histology , Olfactory Nerve/drug effects , Olfactory Nerve/metabolism , Rats , Rats, Sprague-Dawley , Trigeminal Nerve/anatomy & histology , Trigeminal Nerve/drug effects , Trigeminal Nerve/metabolism , Vascular Endothelial Growth Factor A/metabolism
19.
Neurosci Lett ; 446(1): 30-5, 2008 Nov 28.
Article in English | MEDLINE | ID: mdl-18822350

ABSTRACT

Basic fibroblast growth factor (bFGF) is a very important mitogenic factor with proved neurogenesis effects in the central nervous system. Intranasal administration can bypass blood-brain barrier and deliver drugs into the brain directly. We investigated whether intranasal administration of bFGF at later time points after ischemia could promote adult neurogenesis and improve neurologic functions. Rats received bFGF or saline intranasally once daily for 6 consecutive days, starting at 1 day after transient middle cerebral artery occlusion (MCAO). Bromodeoxyuridine (BrdU) was injected at 5 and 6 days after MCAO. Rats were killed at 7 or 28 days after MCAO. Neurogenesis was assessed by immunostaining for BrdU and cell type-specific markers. Neurological functions were evaluated by the modified Neurological Severity Scores. Compared with the control animals, intranasal administration of bFGF improved behavioral recovery without affecting infarct size, and enhanced proliferation of progenitor cells in the subventricular zone and the subgranular zone of the dentate gyrus (DG). Furthermore, the new proliferated cells could differentiate into neurons (BrdU+NeuN+ cells) in the striatum and DG at 28 days after MCAO. Intranasal administration of bFGF offers a non-invasive alternative for the treatment of stroke.


Subject(s)
Cell Proliferation/drug effects , Fibroblast Growth Factor 2/pharmacology , Ischemic Attack, Transient/physiopathology , Neurogenesis/drug effects , Administration, Intranasal , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Bromodeoxyuridine/metabolism , Corpus Striatum/cytology , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dentate Gyrus/cytology , Dentate Gyrus/drug effects , Dentate Gyrus/metabolism , Disease Models, Animal , Fibroblast Growth Factor 2/administration & dosage , Immunohistochemistry , Infarction, Middle Cerebral Artery/physiopathology , Lateral Ventricles/cytology , Lateral Ventricles/drug effects , Lateral Ventricles/metabolism , Male , Neurogenesis/physiology , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Stem Cells/cytology , Stem Cells/drug effects , Stem Cells/metabolism , Time Factors , Treatment Outcome
20.
Neurosci Lett ; 434(2): 212-7, 2008 Mar 28.
Article in English | MEDLINE | ID: mdl-18328626

ABSTRACT

Compelling evidence has shown that extracellular signal-regulated kinase (ERK) is widely expressed in many tissues, including the brain. In the present work, we investigated the temporospatial alterations of ERK1 immunoreactivity in hippocampus and perifocal cortex, and the expression involved in NGF/VEGF-induced neuroprotective effect. We demonstrated that ERK1 expression was first increased in hippocampal CA3/DG 1 h after reperfusion, then it was also increased 6 h after reperfusion in other brain regions, with a peak at day 1-3, and then gradually decreased to basal level at day 14. The expression of caspase-3 was strongly increased 1 h after reperfusion, with peak demonstrated at 3d. NGF/VEGF significantly inhibited the expression of ERK1 and caspase-3. These results suggest that ERK1 signaling pathway may be involved in neuronal cell death and NGF/VEGF-induced neuroprotective effect and there appeared an association between ERK and caspase-3. Inhibition of the ERK signaling pathway might therefore provide an efficient way to prevent neuronal cell death after ischemic cerebral injuries.


Subject(s)
Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Nerve Growth Factor/pharmacology , Neuroprotective Agents/pharmacology , Vascular Endothelial Growth Factor A/pharmacology , Animals , Apoptosis/physiology , Brain Ischemia/pathology , Caspase 3/metabolism , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Hippocampus/metabolism , Hippocampus/pathology , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Male , Nerve Growth Factor/metabolism , Neuroprotective Agents/metabolism , Rabbits , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Vascular Endothelial Growth Factor A/metabolism
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