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1.
ACS Chem Neurosci ; 15(9): 1937-1947, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38630556

RESUMO

The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1ß, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.


Assuntos
Epilepsia do Lobo Temporal , Heparina , Inflamação , Cloreto de Lítio , Nanopartículas Magnéticas de Óxido de Ferro , Estresse Oxidativo , Pilocarpina , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Masculino , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/tratamento farmacológico , Cloreto de Lítio/farmacologia , Heparina/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Ratos Sprague-Dawley , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Anticonvulsivantes/farmacologia
2.
Biomater Sci ; 11(17): 5970-5983, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37486330

RESUMO

The shortage of corneal donors has prompted the development of tissue-engineered corneal grafts as an alternative solution. Currently, amniotic membranes with good biocompatibility are widely used as scaffolds for loading stem cells in the treatment of corneal injury. However, this approach has its limitations. In this study, BMSCs were induced to differentiate into corneal epithelial cells via direct contact co-culture, and platelet-poor plasma was used to prepare fibrin gels, which were compressed to remove excess liquid and then lyophilized to obtain plasma fibrin membranes (PFMs). A tissue-engineered corneal implant with PFMs as a scaffold loaded with BMSCs and corneal epithelial cells was designed and obtained. Scanning electron microscopy showed that PFMs have a uniformly distributed microporous surface that facilitates cell attachment and nutrient transport. The rheological results showed that the freeze-dried and rehydrated PFMs were more rigid than fresh membranes, which makes it easier to use them for transplantation after cell loading. The experimental results of a rat alkali burn cornea injury model showed that PFMs effectively reduced the inflammatory reaction, inhibited fibrosis, and accelerated the healing of corneal wounds. It was also found that some of the BMSCs were successfully implanted into the corneal injury site in rats and differentiated into corneal epithelial cells. These results demonstrate the potential of tissue-engineered corneal implants using BMSCs and corneal epithelial cells and PFMs as scaffolds as a new treatment option for corneal injury.


Assuntos
Queimaduras , Lesões da Córnea , Células-Tronco Mesenquimais , Ratos , Animais , Fibrina/metabolismo , Lesões da Córnea/terapia , Inflamação/metabolismo , Queimaduras/metabolismo , Células Epiteliais , Fibrose , Células da Medula Óssea
3.
Mediators Inflamm ; 2023: 9151967, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469758

RESUMO

There is no effective treatment for peripheral nerve injury-induced chronic neuropathic pain (NP), which profoundly impacts the quality of life of those affected. Transmembraneprotein100 (TMEM100) is considered to be a pain regulatory protein and is expressed in the dorsal root ganglion (DRG) of rats. However, the mechanism of pain regulation and the expression of TMEM100 following various peripheral nerve injuries are unclear. In this study, we constructed two pain models of peripheral nerve injury: tibial nerve injury (TNI) and chronic constriction injury (CCI). This study found that the Paw Withdrawal Mechanical Threshold (PWMT) and Paw Withdraw Thermal Latency (PWTL) of the rats in the two pain models decreased significantly, and the expression of TMEM100 in the DRG of two groups also decreased significantly. Furthermore, the decrease in the CCI group was more obvious than in the TNI group. There was no significant statistical significance (P > 0.05). We constructed an adeno-associated virus 6 (AAV6) vector expressing recombinant fluorescent TMEM100 protein and injected it into the sciatic nerve (SN) of two pain models: CCI and TNI. PWMT and PWTL were significantly increased in the two groups, along with the expression of TMEM100 in the spinal cord and DRG. It also significantly inhibited the activation of microglia, astrocytes, and several inflammatory mediators (TNF- α, IL-1 ß, and IL-6). In summary, the results of this study suggested that TMEM100 might be a promising molecular strategy for the treatment of NP, and its anti-inflammatory effects might play an important role in pain relief.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Ratos Sprague-Dawley , Traumatismos dos Nervos Periféricos/metabolismo , Qualidade de Vida , Medula Espinal/metabolismo , Neuralgia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Hiperalgesia/metabolismo
4.
Eur J Pharmacol ; 897: 173958, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33610598

RESUMO

Hepcidin is the only known hormone negatively regulates systemic iron availability, its excess contributes to anemia of chronic disease (ACD).Heparin has been shown to be an efficient hepcidin inhibitor both in vitro and in vivo, but its powerful anticoagulant activity limits this therapeutic application. To this end, heparin-iron complex was prepared by electrostatic interaction and/or coordination between heparin and dihydroxy iron solution ([Fe(OH)2]+) under the condition of ultrasonic assisted. We assessed the anticoagulant activity of heparin-iron in vitro and vivo by sheep plasma, chromogenic substrate method and tail-bleeding in mice, respectively. Anti-hepcidin effect of heparin-iron was detected in HepG2 cell and LPS induced acute inflammation mice by qRT-PCR and ELISA. Turpentine-induced anemia mice were established to evaluate the effect of heparin-iron in ACD. Mice were treated with heparin-iron for 4 weeks. The results indicated that heparin-iron has significantly reduced anticoagulant activity in vitro and in vivo, strongly decreases hepcidin mRNA and IL-6 induced high level of secreted hepcidin in HepG2 cell. Heparin-iron was also found to cause a reduction on hepcidin expression through BMP/SMAD and JAK/STAT3 pathways in LPS induced acute inflammation model in mice. In ACD mice, heparin-iron could lower elevated serum hepcidin and improve anemia. These findings demonstrated low anticoagulant heparin-iron has potential applications for the treatment of ACD with high hepcidin levels.


Assuntos
Anemia/prevenção & controle , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Compostos Férricos/farmacologia , Heparina/farmacologia , Hepcidinas/antagonistas & inibidores , Compostos de Ferro/farmacologia , Fígado/efeitos dos fármacos , Anemia/etiologia , Anemia/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Modelos Animais de Doenças , Feminino , Compostos Férricos/uso terapêutico , Células Hep G2 , Heparina/análogos & derivados , Heparina/uso terapêutico , Hepcidinas/genética , Hepcidinas/metabolismo , Humanos , Inflamação/complicações , Compostos de Ferro/análogos & derivados , Janus Quinases/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Fator de Transcrição STAT3/metabolismo , Carneiro Doméstico , Transdução de Sinais , Proteínas Smad/metabolismo , Terebintina
5.
Carbohydr Polym ; 207: 79-90, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30600066

RESUMO

Endostatin (ES) has attracted considerable attention for the treatment of anti-angiogenesis-related disorders. An 11-amino-acid peptide (ES2, IVRRADRAAVP) from the amino terminal of ES is of interest because it is the main active fragment of ES. However, both ES and ES2 have a poor stability and a short half-life, and other disadvantages need to be further resolved. Thus, we conjugated ES2 to glycol-split heparin derivatives (GSHPs) to yield the polymer-peptide conjugate, GSHP-ES2. This study showed that GSHP-ES2 exhibited increased stability, a wider pH activity range, better inhibition of endothelial cell proliferation, migration and tube formation in vitro, better anti-angiogenic activity and a longer half-life in vivo compared with ES2. These results also indicate that GSHP-ES2 has good potential for the treatment of angiogenesis-related diseases, either alone or in combination with other chemicals.


Assuntos
Inibidores da Angiogênese/farmacologia , Endostatinas/farmacologia , Glicopeptídeos/farmacologia , Heparina/química , Oligopeptídeos/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/farmacocinética , Inibidores da Angiogênese/toxicidade , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Galinhas , Estabilidade de Medicamentos , Endostatinas/síntese química , Endostatinas/farmacocinética , Endostatinas/toxicidade , Feminino , Glicopeptídeos/síntese química , Glicopeptídeos/farmacocinética , Glicopeptídeos/toxicidade , Meia-Vida , Humanos , Camundongos Endogâmicos BALB C , Oligopeptídeos/síntese química , Oligopeptídeos/farmacocinética , Oligopeptídeos/toxicidade , Peixe-Zebra
6.
J Mater Sci Mater Med ; 23(9): 2291-302, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22661248

RESUMO

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration with different biomaterials. Nerve autografting is the most common surgical procedure currently used to repair nerve defects as a gold standard. To address the disadvantages of limited availability of donor nerves and donor site morbidity, we have fabricated chitosan conduits and seeded them combined with bone marrow mesenchymal stem cells (BMSCs) as an alternative. The conduits were tested for efficacy in bridging the critical gap (8 mm) in sciatic nerves of adult rats, which including sciatic nerve function index (SFI), ethology observation, histologic detection, immunohistochemistry detection. The BMSCs were tested for survival rate and differentiation by fluorescence labeling. Six weeks after operation, the SFI, average regenerated fiber density, and fiber diameter in nerves bridged with BMSCs were similar to those treated with autograft, but significantly higher than those bridged with chitosan conduits only (P < 0.05) because of the differentiation of BMSCs. Evidence is thus provided to support the effect of using multi-channel chitosan conduits seeded with BMSCs to treat critical defects in peripheral nerves. This provides the basis to pursue chitosan and BMSCs combination is an effective method to improve the nerve healing, which may be used as an alternative to the conventional nerve autografts.


Assuntos
Células da Medula Óssea/fisiologia , Quitosana/farmacologia , Regeneração Tecidual Guiada/métodos , Células-Tronco Mesenquimais/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Alicerces Teciduais , Animais , Células da Medula Óssea/citologia , Células Cultivadas , Quitosana/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Atividade Motora/fisiologia , Regeneração Nervosa/fisiologia , Próteses e Implantes , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Nervo Isquiático/citologia , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química
7.
Molecules ; 17(3): 3243-58, 2012 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-22418927

RESUMO

A biodegradable, biocompatible poly(chitosan-g-lactic acid) (PCLA) scaffold was prepared and evaluated in vitro and in vivo. The PCLA scaffold was obtained by grafting lactic acid (LA) onto the amino groups on chitosan (CS) without a catalyst. The PCLA scaffolds were characterized by Fourier Transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The biodegradabilty was determined by mass loss in vitro, and degradation in vivo as a function of feed ratio of LA/CS. Bone marrow mesenchymal stem cell (BMSC) culture experiments and histological examination were performed to evaluate the PCLA scaffolds' biocompatibility. The results indicated that PCLA was promising for tissue engineering application.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis/síntese química , Quitosana/síntese química , Teste de Materiais , Poliésteres/síntese química , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Células da Medula Óssea/fisiologia , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Quitosana/química , Quitosana/metabolismo , Concentração de Íons de Hidrogênio , Células-Tronco Mesenquimais/fisiologia , Camundongos , Muramidase/química , Poliésteres/química , Poliésteres/metabolismo , Porosidade , Distribuição Aleatória , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Tela Subcutânea/patologia , Propriedades de Superfície
8.
Biomed Pharmacother ; 65(2): 111-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21227626

RESUMO

Low-molecular-weight heparin has the potential for the treatment of ulcerative colitis, and targeted drug delivery to the colon is important for topical treatment of this disease, so low-molecular-weight heparin oral colon-specific delivery capsule was prepared, and the in vitro and in vivo drug release behavior was investigated. The macroscopical and histological scoring systems, wet colon mass index and myeloperoxidase activity were assessed to evaluate the efficacy of the capsule after administered orally to experimental colitis mice. Serum levels, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and a link factor of blood coagulation and inflammation factor Xa (FXa) were assayed by enzyme-linked immunosorbent assay. The expression of Musashi-1 (as an intestinal stem cell marker) in the colons was assessed by immunohistochemical analysis. The in vitro and in vivo drug release studies clearly indicated that the specific coated capsules were capable of protecting low-molecular-weight heparin from releasing in stomach and small intestine, while specifically delivering at colon. The oral colon-specific delivery capsule of low-molecular-weight heparin could attenuate macroscopic and histological features of colitis. The results showed that low-molecular-weight heparin oral colon-specific delivery capsule significantly decreased the serum levels of TNF-α, IL-6 as well as FXa, while increased the expression of Musashi-1 in colon compared with acetic acid-induced ulcerative colitis model group. The results showed that low-molecular-weight heparin oral colon-specific delivery capsule had the potential for treatment of inflammatory bowel disease.


Assuntos
Anticoagulantes/farmacologia , Colite Ulcerativa/tratamento farmacológico , Dalteparina/farmacologia , Sistemas de Liberação de Medicamentos , Administração Oral , Animais , Anticoagulantes/administração & dosagem , Colite Ulcerativa/patologia , Colo/metabolismo , Dalteparina/administração & dosagem , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fator Xa/metabolismo , Feminino , Interleucina-6/sangue , Masculino , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fator de Necrose Tumoral alfa/sangue
9.
Biomed Pharmacother ; 64(7): 441-5, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20359854

RESUMO

The objective of this study was to investigate the effect and possible mechanism of rectally administered low molecular weight heparin (LMWH) on experimental ulcerative colitis. LMWH rectal suppository was prepared and its efficacy was studied by macroscopical and histological scoring systems as well as myeloperoxidase activity. Serum levels, including tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and a link factor of blood coagulation and inflammation factor Xa (FXa) were assayed by enzyme-linked immunosorbent assay. The expression of Musashi-1 (as an intestinal stem cell marker) in the colons was assessed by immunohistochemical analysis. The results showed that LMWH rectal suppository significantly decreased serum levels of TNF-α, IL-6 as well as FXa, while increased the expression of Musashi-1 in colon compared with acetic acid induced ulcerative colitis model group. All these preliminary results indicate LMWH rectal suppository is promising for treatment of ulcerative colitis.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/farmacologia , Administração Retal , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Citocinas/sangue , Fator Xa/análise , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Interleucina-6/sangue , Masculino , Camundongos , Peroxidase/análise , Polietilenoglicóis , Supositórios , Fator de Necrose Tumoral alfa/sangue
10.
J Mater Sci Mater Med ; 21(5): 1713-20, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20101439

RESUMO

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test chitosan conduit to use in peripheral nerve reconstruction, either alone or combined with bone marrow mesenchymal stem cells (BMSCs). In this study, the roles of the degree of deacetylation (DD) and molecular weight of chitosan on some biological properties of chitosan films, including hydrophilicity, degradation and BMSCs affinity were investigated. The molecular weight of Chitosans used are 5 x 10(4) Da, 2 x 10(5) Da, 5 x 10(5) Da, 1 x 10(6) Da, the deacetylation degrees are 85, 95%, respectively. The affinity of eight kinds of Chitosans to the BMSCs was assessed by MTT assay, the contact angle and the degradation time of the materials in vivo were also measured. Chitosans with the molecular weight of 1 x 10(6) Da and DD of 95% can significantly promote the survival and outgrowth of cells, which have better hydrophilicity and can remain integrity even after 8 to 16 weeks, all of above meet the requirement of nerve engineering. The BMSCs we transplanted can differentiate into neural stem cells in vivo, and the materials we selected combined with BMSCs can bridge 8-mm-long neural gap better resulting from the differentiation effects of the BMSCs.


Assuntos
Quitosana/farmacologia , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa/fisiologia , Animais , Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Quitosana/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Regeneração Nervosa/efeitos dos fármacos , Nervos Periféricos/metabolismo , Próteses e Implantes , Regeneração/efeitos dos fármacos
11.
Cancer Chemother Pharmacol ; 62(3): 509-15, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18008069

RESUMO

PURPOSE: The over-expression of glutathion S-transferase Pi (GSTpi) in tumors and inhibitory effect of GSTpi to JNK are two possible causes of the development of drug-resistance in chemotherapy. This research is to develop a novel pH-controlled NO donor to inhibit GSTpi(and to activate the JNK/c-Jun pathway (omit "to induce apoptosis"). METHODS: Four 4-Aryl-1,3,2-oxathiazolylium-5-olate (OZO) derivatives with varying aryl para-substitutions (-H, -CF(3), -Cl, and -OCH(3)) were synthesized. Anticancer activity was determined by MTS assay. GST activity was measured with spectrophotometry using 1-chlro-2,4-dinitrobenzene (CDNB) and GSH as substrates. (omit "Apoptosis was evaluated by annexin V staining and flow cytometry"). c-Jun N-terminal kinase 1 (JNK1) association with GSTpi and activation of c-Jun were evaluated with immunoprecipitation and western blot. RESULTS: OZO derivatives showed anticancer effect against leukemia and breast cancer cells by MTS assay. The relative potency of their anticancer effects is OZO-H > OZO-Cl, OZO-OMe > OZO-CF(3). The anticancer activity of these compounds was correlated with their inhibition of GST activity in cancer cells. The immunoprecipitation result showed that the treatment of OZO-H released JNK1 from GSTpi-JNK1 complex. Consequently, the treatment of OZO-H in cancer cells induced JNK1 phophorylation and activated c-Jun in cancer cells. CONCLUSION: OZO-H is a novel GST inhibitor to release JNK1 for activation of JNK/c-Jun pathway (original is "c-Jun to trigger apoptosis in cancer cells"). It provides a new class of GST target compound for anticancer therapy.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Glutationa Transferase/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Tiazóis/farmacologia , Antineoplásicos/química , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Glutationa/metabolismo , Humanos , Células K562 , Estrutura Molecular , Transdução de Sinais , Relação Estrutura-Atividade , Tiazóis/química
12.
World J Gastroenterol ; 10(23): 3485-9, 2004 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-15526370

RESUMO

AIM: To investigate the effect of dermatan sulfate (DS) derivatives on platelet surface P-selectin expression and blood activated protein C (APC) activity in patients with inflammatory bowel disease (IBD), and to clarity the anti-inflammatory mechanism of DS derivatives. METHODS: Dermatan sulfate (DS) was sulfated with chlorosulfonic acid to prepare polysulfated dermatan sulfate (PSDS). The major disaccharides of DS and PSDS were determined by 1H nuclear magnetic resonance spectroscopy (1H-NMR) and 13C-NMR. Both DS and PSDS were depolymerized with hydrogen peroxide. The fragments were separated by gel filtration chromatography. The effects of DS derivatives on P-selectin expression were assayed by ELISA method, and blood APC activity was assayed by the synthetic chromogenic substrate method. RESULTS: The major disaccharides of DS and PSDS were IdoA-1-3-GalNAc-4-SO3 and IdoA-2SO3-1-3-GalNAc4, 6-diSO3, respectively. Compared with the adenosine diphosphate stimulated group and IBD control group, DS and its derivatives all had significant inhibitory effects on P-selectin expression (P<0.01), but there was no difference between DS-derived oligosaccharides (DSOSs) and PSDS-derived oligosaccharides (PSDSOSs). The experiments on APC activity showed that DS and its derivatives all enhanced APC activity. The most active DSOS was the one with a relative molecular weight (Mr) of 4,825, which enhanced the APC activity from 106.5+/-11.5% to 181.8+/-22.3% (P<0.01). With the decrease of Mr, the activity of DSOSs decreased gradually. The effect of PSDS on APC activity enhancement was more significant than that of DS, and the APC activity was raised to 205.2+/-22.1% (P<0.01). All the PSDSOSs were more active than DSOSs on the basis of comparable Mr. With the decrease of Mr, the activity of PSDSOSs increased gradually, and the most active PSDSOS was PSDSOS3 with Mr of 2,749, which enhanced the APC activity to 331.2+/-27.8% (P<0.01), then the activity of PSDSOSs decreased gradually. CONCLUSION: DS and its derivatives can significantly inhibit P-selectin expression on platelet surface, but the effect has no correlation with DS molecular mass and sulfation. The effect of DS or its derivatives on APC activity at molecular level involves complex mechanisms that depend on the molecular mass, the degree of sulfation, and the heterogeneous composition of DS. On the same molecular size, the higher the degree of DS sulfation, the more significant the effect on enhancing APC activity.


Assuntos
Anticoagulantes/farmacologia , Plaquetas/efeitos dos fármacos , Dermatan Sulfato/farmacologia , Doenças Inflamatórias Intestinais/metabolismo , Selectina-P/metabolismo , Proteína C/metabolismo , Anticoagulantes/química , Plaquetas/imunologia , Plaquetas/metabolismo , Isótopos de Carbono , Dermatan Sulfato/química , Humanos , Técnicas In Vitro , Doenças Inflamatórias Intestinais/imunologia , Espectroscopia de Ressonância Magnética , Prótons , Sulfatos/química , Sulfatos/farmacologia
13.
World J Gastroenterol ; 10(10): 1513-20, 2004 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-15133864

RESUMO

AIM: To study the different therapy for different types of ulcerative colitis (UC) in China. METHODS: Among 102 UC patients, 42 chronic relapse type UC patients were randomly divided into olsalazine sodium treatment group (n=21) and SASP group (n=21). Clinical effects and safety were observed in the 2 groups. Forty-two first episode type UC patients were randomly divided into Heartleaf houttuynia herb treatment group (n=21) and SASP group (n=21). Clinical effects were observed in the 2 groups while ultrastructure of colonic mucosa, ICAM-1 and the pressure of distant colon were studied in Heartleaf houttuynia herb group. Eighteen patients (8 males, 10 females) with refractory UC and unresponsive to high-dose prednisolone and sulfasalazine therapy more than one month were treated with Kangshuanling (7200 U/d). Prednisolone was gradually stopped and sulfasalazine was maintained. Stool frequency, rectal bleeding, colonoscopy, general well-being, histology were observed and CD62p, CD63, CD54, Pgp-170 (flow cytometry), TXA2 (RIA), blood platelet aggregation rate and thrombosis length in vitro were assessed. RESULTS: In the 42 chronic relapse type UC patients, the overall clinical effects of olsalazine sodium group (complete remission in 16, improvement in 4, inefficiency in 1) were better than those of SASP group (complete remission in 10, improvement in 4, inefficiency in 7, P<0.05). Symptomatic remission of olsalazine sodium group (complete remission in 15, partial remission in 5, inefficiency in 1) was better than that of SASP group (complete remission in 10, partial remission in 5, inefficiency in 6, P<0.05). The colonoscopic remission of olsalazine sodium group(complete remission in 11, partial remission in 9, inefficiency in 1) was better than that of SASP group (complete remission in 7, partial remission in 8, inefficiency in 6, P<0.05). The histologic remission of olsalazine sodium group (complete remission in 13, partial remission in 7, inefficiency in in 1) was better than that of SASP group (complete remission in 6, partial remission in 10, inefficiency in 5, P<0.05). The side effects of gastrointestinal tract in olsalazine sodium group were less than those of SASP group except for frequency of watery diarrhea. No other side effects were observed in olsalazine sodium group while ALT increase, WBC decrease and skin eruption were observed in SASP group. Two patients relapsed in olsalazine sodium group while 8 cases relapsed in SASP group during the flow-up period (from six months to one year). In the 42 first episode type UC patients, the clinical effect of Heartleaf houttuynia herb group (complete remission in 20, 95.2%; improvement in 1, 4.8%) was better than that of SASP group (complete remission in 15, 72.4%, improvement in 5, 23.8%; inefficiency in 1, 3.8%, P<0.01). The time of stool frequency recovering to normal (5.6+/-3.3 d), and blood stool disappearance (6.7+/-3.8 d) and abdominal pain disappearance (6.1+/-3.5 d) in Heartleaf houttuynia herb group was all shorter than that in SASP group (9.5+/-4.9 d, 11.7+/-6.1 d, 10.6+/-5.3 d, P<0.01). Heartleaf houttuynia herb could inhibit the epithelial cell apoptosis of colonic mucous membrane and the expression of ICAM-1 (45.8+/-5.7% vs 30.7+/-4.1%, P<0.05). Compared with normal persons, the mean promotive speed of contraction wave stepped up (4.6+/-1.6 cm/min vs 3.2+/-1.8 cm/min, P<0.05) and the mean amplitude of the wave decreased (14.2+/-9.3 kPa vs 18.4+/-8.0 kPa, P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, these 2 indexes improved significantly (17.3+/-8.3 kPa, 3.7+/-1.7 cm/min, P<0.05). In normal persons, the postprandial pressure of sigmoid (2.9 +/-0.9 kPa) was higher than that of descending colon (2.0+/-0.7 kPa) and splenic flexure (1.7+/-0.6 kPa), while the colonic pressure (1.5+/-0.5 kPa, 1.4+/-0.6 kPa, 1.3+/-0.6 kPa) decreased significantly (P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold of distant colon (67.3+/-18.9 mL) in active UC patients decreased significantly compared with that of normal persons (216.2+/-40.8 mL, P<0.05) and recovered to normal after treatment with Heartleaf houttuynia herb(187.4+/-27.2 mL, P<0.05). In the 18 refractory UC patients with platelet activation, after more than 4 wk of combined Kangshuanling and sulfasalazine therapy, 16 patients achieved clinical remission, with a highly significant statistical difference (P<0.01) between pre-and post-treatment mean scores for all disease parameters: stool frequency (8.2/d vs 1.6/d), rectal bleeding (score 2.7 vs 0.3), colonoscopy (score 2.6 vs 1.1), histology (score 12.0 vs 5.0), general well being (score 4.0 vs 0.6) and CD62p (8.0+/-3.1% vs 4.1+/-1.8%), CD63 (6.3+/-2.1% vs 3.2+/-1.6%), TXA2 (548+/-85 ng/L vs 390+/-67 ng/L), platelet aggregation rate (43.2+/-10.7% vs 34.8+/-8.1%), thrombosis length in vitro (2.3+/-0.6 cm vs 1.8+/-0.3 cm), CD54 in blood (26.9+/-6.9% vs 14.4+/-5.1%), CD54 in tissues (51.1+/-6.2% vs 23.1+/-4.1%), Pgp-170 in blood (18.9+/-3.9% vs 10.4+/-2.7%), Pgp-170 in tissues (16.5+/-3.2% vs 10.2+/-2.3%, P<0.01 or 0.05). CONCLUSION: Based on the characteristics of UC cases in China, different therapy should be given to different types of UC with expected satisfactory results.


Assuntos
Ácidos Aminossalicílicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Prednisolona/uso terapêutico , Sulfassalazina/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Antígenos CD/sangue , China , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Feminino , Houttuynia , Humanos , Masculino , Ativação Plaquetária , Trombose , Tromboxano A2/sangue
14.
World J Gastroenterol ; 9(10): 2274-7, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14562392

RESUMO

AIM: To evaluate the protective effects of transplanted and mobilized bone marrow stem cells (BMSCs) on mice with severe acute pancreatitis (SAP) and to probe into their possible mechanisms. METHODS: A mouse model of SAP induced by intraperitoneal injections of L-arginine was employed in the present study. Two hundred female Balb/c mice weighing 18-22 g were randomly assigned into 4 groups. Group A was the stem cell mobilized group treated by injection of granulocyte-colony stimulating factor (G-CSF) into mice for 4 days at a dose of 40 microg.kg(-1).d(-1) before induction of SAP. Group B was the group of BMSCs transplantation, in which the mice were given the isolated BMSCs via the tail vein 4 days prior to induction of SAP. Group C served as the model control and only SAP was induced. The mice without induction of SAP in group D acted as the normal control. At the time of animal sacrifice at 24, 48 and 72 h after induction of SAP, blood samples were obtained and prepared to detect serum amylase, while the abdominal viscera were examined both grossly and microscopically for the observation of pathological changes. RESULTS: The mortality of mice in the model control, groups A and B was 34%, 8% and 10% respectively within 72 h after induction of SAP. The serum level of amylase in the model control was significantly increased at all time points after induction of SAP as compared with that of the normal control (P<0.05-0.01). When the mice were pretreated with BMSCs' transplantation or G-CSF injection, their serum level of amylase was significantly reduced at 48 h and 72 h after induction of SAP in comparison with that of the model control (P<0.05-0.01). In accordance with these observations, both gross and microscopic examinations revealed that the pathological changes of SAP in mice pretreated with BMSCs transplantation or G-CSF injection were considerably attenuated as compared with those in the model control at all observed time points. CONCLUSION: Both transplanted allogenic and mobilized autologous BMSCs can protect mouse pancreas from severe damage in the process of SAP.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pancreatite/terapia , Doença Aguda , Amilases/sangue , Animais , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Pâncreas/patologia , Pancreatite/mortalidade , Pancreatite/patologia , Índice de Gravidade de Doença , Transplante Homólogo
15.
World J Gastroenterol ; 8(1): 158-61, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11833094

RESUMO

AIM: To analyze the characteristics of ulcerative colitis(UC) in China. METHODS: From 1981 to 2000, a total of 10218 patients of UC reported in Chinese medical literature and including our cases diagnosed were analyzed according to the diagnostic criteria of Lennard-Jones. RESULTS: The number of cases increased by 3.08 times over the past 10 years (2506 patients were diagnosed from 1981 to 1990 while 7512 patients were diagnosed from 1991 to 2000). Lesion range were described in 7966 patients, 5592 (70.20%) were proctosigmoiditis or proctitis, 1792(22.50%) left-sided colitis, 582(7.30%) pancolitis. Among the 8122 patients, 2826 (34.8%) had first episode, 4272 (52.6%) had chronic relapse, 869 (10.7%) were of chronic persist type, 154 (1.9%) were of acute fulminant type. The course of the illness were described in 5867 patients, 4427(75.5%) were less than 5 years, 910 (15.5%) between 5 and 10 years,530 (9.1%) more than 10 years. Six hundred and sixteen patients 618 patients(6.1%) had extraintestinal manifestations. The mean age at the diagnosis was 40.7 years( range 6-80 years, and the peak ages 30-49 years). The male to female ratio was 1.09. Among 270 patients diagnosed in our hospital,36 had histories of smoking, there was no negative association between the severity of UC and smoking(P>0.05), 21 smokers were followed up for one year, 15 of them had given up smoking when the disease were diagnosed, and one year later, 7 patients relapsed, another 6 patients continued smoking, and one year later,2 patients relapsed. Among 270 UC patients diagnosed in our hospital, 4 patients(1.48%) from 2 families had familial history of UC. Treatment was mentioned in 6859 patients, only 5-ASA and/or corticosteroid only in 1276 patients(18.6%), only Chinese herbs in 1377 patients(20.1%), combined Chinese and western medicine in 4056 patients(59.1%), surgery was performed in 87 patients(1.3%),other treatments in 63 patients(0.9%). CONCLUSIONS: In China, number of UC patients increased significantly in the past 10 years. Lesions are commonly located to left side colon. The course is short with rare extraintestinal manifestations. The age of onset is relatively high. Males and females are nearly equally affected. No negative relation was found between smoking and severity of the disease. Familial relatives are rarely involved Traditional Chinese medicine(TCM) is widely used in the treatment of UC.


Assuntos
Colite Ulcerativa/epidemiologia , China/epidemiologia , Colite Ulcerativa/patologia , Colite Ulcerativa/terapia , Medicamentos de Ervas Chinesas , Humanos
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