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1.
J Dairy Sci ; 104(12): 12496-12507, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34593232

RESUMO

This study evaluated the effects of incremental tributyrin supplementation in pasteurized waste milk on growth performance, health, and blood metabolism of dairy calves before and after weaning. Forty-eight newborn female Holstein dairy calves (39.6 ± 2.75 kg; mean ± standard deviation) were blocked by age and randomly assigned to 3 treatments: pasteurized waste milk (1) without supplementation, (2) with 1 g/L of tributyrin products (unprotected solid powder; containing 35% tributyrin), or (3) with 2 g/L of tributyrin products. The calves were weaned on d 56 and were raised until d 77. Data were analyzed for the preweaning, postweaning, and overall periods. The results showed that starter intake and hay intake were not different among treatments in any period of the trial, but the crude protein intake tended to increase linearly with tributyrin supplementation during the overall period. Although tributyrin supplementation had no effects on body weight during preweaning and overall periods, body weight increased linearly with tributyrin supplementation postweaning. The average daily gain tended to increase linearly during postweaning and overall periods. No effects were observed on feed efficiency in any period. A positive linear relationship between body length and tributyrin supplementation was observed during the postweaning period, but no differences were found for the other body structural measurements in any period. The results of diarrhea showed that tributyrin concentration had a negative linear relationship with diarrhea frequency during preweaning and overall periods. The rectal temperature did not differ among treatments in any period, but a treatment × week effect for rectal body temperature was observed. For blood metabolism, tributyrin supplementation had no effects on insulin, growth hormone, total protein, albumin, or globulin. No differences were found in serum amyloid A concentration in any of the periods, yet haptoglobin concentration decreased linearly with increasing tributyrin concentration during postweaning and overall periods. Endothelin concentration showed a tendency to decrease linearly during preweaning and postweaning periods and decreased linearly with tributyrin supplementation during the overall period. An increasing tributyrin concentration was associated with a negative linear relationship with IL-1ß concentration during the preweaning period, and no differences were found in the other periods. The concentration of IL-6 and tumor necrosis factor α were not different among treatments in any of the periods. These data suggest that increasing the concentration of tributyrin in pasteurized waste milk could increase growth performance and health of dairy calves, and incremental tributyrin supplementation could linearly reduce haptoglobin, endothelin, and IL-1ß concentrations, indicating a positive effect of tributyrin on alleviating oxidative stress and inflammatory status of dairy calves. Calves fed pasteurized waste milk supplemented with tributyrin products (containing 35% tributyrin) at 2 g/L compared with 1 g/L of milk had more improved growth and health.


Assuntos
Ração Animal , Leite , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta , Suplementos Nutricionais , Feminino , Triglicerídeos , Desmame
2.
Tech Coloproctol ; 25(6): 683-691, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32572664

RESUMO

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be an effective treatment for peritoneal tumors; whether preventive HIPEC after radical resection for T4 stage colon adenocarcinoma could decrease peritoneal recurrence remains unknown. The aim of the present study was to compare peritoneal recurrence and short-term survival in patients with T4 stage colon adenocarcinoma undergoing HIPEC plus adjuvant chemotherapy or adjuvant chemotherapy alone following surgery. METHODS: We retrospectively reviewed T4 stage colon adenocarcinoma patients who had radical tumor resection at our institution between January 2014 and January 2019. Clinical data were extracted from the database at our institution, and patient survival and long-term complications were assessed through repeated outpatient examinations and telephone interviews. RESULTS: A total of 352 patients were included in this study; 157 patients received postoperative HIPEC plus adjuvant chemotherapy (HIPEC group), 195 patients received adjuvant chemotherapy alone (conventional chemotherapy group). Forty-one (26.1%) patients in the HIPEC group had a peritoneal recurrence and the peritoneum was the first site of tumor recurrence in 6 (14.6%) of them. However, 73 (37.4%) patients experienced peritoneal recurrence in the conventional group, and the peritoneum was the first site of tumor recurrence in 25 (34.2%) (p = 0.019). Disease-free survival in the HIPEC group at 1 and 3 years was 93.3% and 61.1%, respectively, versus 89.3% and 51.7% in the conventional chemotherapy group (p = 0.038). Overall survival in the HIPEC group at 1 and 3 years was 100.0% and 82.7%, respectively, versus 100.0% and 76.9% in the conventional chemotherapy group (p = 0.420). The two groups did not differ with respect to severe complications. CONCLUSIONS: Preventive HIPEC after radical surgery may decrease peritoneal recurrence and promote disease-free survival for T4 stage colon adenocarcinoma. Large-scale randomized controlled studies are needed to confirm the results of our study.


Assuntos
Adenocarcinoma , Hipertermia Induzida , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Colo , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Perfusão , Estudos Retrospectivos , Taxa de Sobrevida
3.
Zhonghua Shao Shang Za Zhi ; 36(4): 304-307, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32340421

RESUMO

Objective: To observe the effect of liquid paraffin as adjuvant therapy in treating residual wounds of patients with severe burns. Methods: From January 2016 to October 2017, 58 patients with residual wounds in the later stage of severe burns were admitted to Beijing Jishuitan Hospital. Those patients met the inclusion criteria of this study and were enrolled in this retrospective cohort study. All the patients received wound disinfection, petrolatum gauze dressing change and silver ion-bearing antimicrobial dressing every other day to treat the residual wound until wound healing. From January to November 2016, 29 patients who were treated with iodophor and normal saline to clean and disinfect the wound before dressing change were enrolled in normal saline group, including 22 males and 7 females, aged (38±12) years. From December 2016 to October 2017, 29 patients who were treated with iodophor and liquid paraffin to clean and disinfect the wound before dressing change were enrolled in liquid paraffin group, including 20 males and 9 females, aged (37±12) years. The effective rate of treatment, infection control rate, and bacterial positive ratio of wound on post first treatment day (PFTD) 7, 14, and 21 and the complete wound healing time of patients were compared between the two groups. Data were statistically analyzed with independent sample t test, Wilcoxon rank-sum test, chi-square test, and Pearson chi-square test, continuity correction chi-square test, and Fisher's exact probability test after Bonferroni correction. Results: (1) On PFTD 7, 14, and 21, the effective rates of wound treatment in patients of liquid paraffin group were 34% (10/29), 59%(17/29), and 79%(23/29), respectively, which were significantly higher than 10% (3/29), 24% (7/29), and 38% (11/29) of normal saline group (χ(2)=5.857, 7.108, 10.235, P<0.05 or P<0.01). (2) The wound infection control rates in patients of liquid paraffin group on PFTD 7 and 14 were 79% (23/29) and 90% (26/29), respectively, which were significantly higher than 31% (9/29) and 52% (15/29) of normal saline group (χ(2)=13.663, 8.321, P<0.01). The wound infection control rate in patients of liquid paraffin group on PFTD 21 was 100% (29/29), which was significantly higher than 69% (20/29) of normal saline group (P<0.01). (3) The bacterial positive ratios in the wounds of liquid paraffin group were similar to those of normal saline group on PFTD 7 and 14 (χ(2)=2.097, 2.583, P>0.05). On PFTD 21, the wound bacterial positive ratio of liquid paraffin group was 8% (3/39), which was significantly lower than 49% (17/35) of normal saline group (χ(2)=13.625, P<0.01). (4) The complete wound healing time of patients in liquid paraffin group was 15.0 (11.0, 20.0) d, which was significantly shorter than 22.0 (15.0, 27.5) d of normal saline group (Z=2.256, P<0.05). Conclusions: In the treatment of residual wounds of severe burn patients, liquid paraffin as adjuvant therapy can effectively improve the treatment effective rate and the infection control rate of wounds, decrease the bacterial positive ratio, and shorten the wound healing time.


Assuntos
Queimaduras , Adulto , Bandagens , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óleo Mineral , Estudos Retrospectivos , Cicatrização
4.
Sci Rep ; 8(1): 12546, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30135449

RESUMO

Although there is a huge progress in complementary-metal-oxide-semiconductor (CMOS) technology, construction of an artificial neural network using CMOS technology to realize the functionality comparable with that of human cerebral cortex containing 1010-1011 neurons is still of great challenge. Recently, phase change memristor neuron has been proposed to realize a human-brain level neural network operating at a high speed while consuming a small amount of power and having a high integration density. Although memristor neuron can be scaled down to nanometer, integration of 1010-1011 neurons still faces many problems in circuit complexity, chip area, power consumption, etc. In this work, we propose a CMOS compatible HfO2 memristor neuron that can be well integrated with silicon circuits. A hybrid Convolutional Neural Network (CNN) based on the HfO2 memristor neuron is proposed and constructed. In the hybrid CNN, one memristive neuron can behave as multiple physical neurons based on the Time Division Multiplexing Access (TDMA) technique. Handwritten digit recognition is demonstrated in the hybrid CNN with a memristive neuron acting as 784 physical neurons. This work paves the way towards substantially shrinking the amount of neurons required in hardware and realization of more complex or even human cerebral cortex level memristive neural networks.


Assuntos
Modelos Neurológicos , Redes Neurais de Computação , Neurônios , Semicondutores , Encéfalo/citologia , Encéfalo/fisiologia , Escrita Manual , Humanos
5.
J Anim Sci ; 92(12): 5704-15, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25367513

RESUMO

On a global scale, most beef is produced from grazing pastures or rangelands. Certain limitations exist, however, such as not having adequate animal rates of gain for marbling and availability of adequate forage nutritional value and quantity for constant animal weight gains. In the last 20 yr, there has been an increased interest in forage-fed beef for multiple reasons (health related, environmental concerns, and welfare issues). Starting on June 5, 13, 14, and 8 in 4 consecutive yr, 54 steers (initial BW=259±5.6 kg; average of 9 mo of age) were randomly allotted to 3 yr-round forage systems. Each system occupied 6 ha/replicate and had the same stocking rate. System 1 had annual ryegrass (Lolium multiflorum) for winter grazing and bermudagrass (Cynodon dactylon) for summer grazing; while Systems 2 and 3 added rye and a clover mix to the ryegrass and diversified the use of pastures in the fall (dallisgrass [Paspalum dilatatum] and clovers [Trifolium spp.]). System 3 added the use of annual summer forages. During their respective growing season for each forage or forage mix, mass and height did not limit animal performance; however, there was a sampling date effect (P<0.05) for nutritive value variables since it decreased as forages became mature. The ADG observed (0.44 kg) for all systems (P=0.78) during summer was lower than expected and might have been limited by the observed temperature as well as forage nutritive value. Systems 1 and 2 had more grazing days (P=0.03) during summer (155 and 146 d, respectively) compared to System 3 (132 d) due to the greater pasture area of bermudagrass in those systems. Steers in System 3 were fed more hay for a longer period of time (P<0.05) than on the other 2 systems. System 1 and 2 produced more hay per hectare than System 3 (P<0.05). No differences (P>0.05) were detected between systems in ADG year round, during the winter season, or carcass characteristics. Return over total direct costs and total specified expenses were greater for Systems 1 and 2, while System 3 was the lowest. Hay making and bale sales played a major role in explaining the economic results of this study. Where possible, year-round forage systems are a viable alternative for forage-fed beef production; however, the low gains during summer and forage availability during the transition period when hay is necessary deserve further research to find alternatives to improve productivity during those times of the year.


Assuntos
Ração Animal/economia , Ração Animal/normas , Bovinos/fisiologia , Dieta/veterinária , Carne/economia , Estações do Ano , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Composição Corporal/fisiologia , Cynodon , Dieta/economia , Lolium , Louisiana , Masculino , Medicago , Valor Nutritivo/fisiologia , Aumento de Peso/fisiologia
6.
Genet Mol Res ; 13(3): 5025-35, 2014 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-25062491

RESUMO

In Brassicaceae, a self-incompatibility (SI) system mediates pollen-pistil interactions. Self-pollen could be recognized and rejected by incompatible pistils. Several components involved in the SI response have been determined, including S-locus receptor kinase (SRK), S-locus cysteine-rich protein/S-locus protein 11, and arm repeat-containing protein 1 (ARC1). However, the components involved in the SI system of Brassicaceae are not fully understood. Here, we detected expression patterns of 24 SI-related genes in non-heading Chinese cabbage (Brassica campestris ssp chinensis Makino) after compatible and incompatible pollination, and potential interaction relationships of these genes were predicted. SRK and ARC1 transcripts increased initially 0.25 h after incompatible pollination, while kinase-associated protein phosphatase had an expression pattern that was opposite that of SRK transcripts during self-pollination. Plant U-box 8 was not required in the SI response of non-heading Chinese cabbage. Our results showed that the SI signal of non-heading Chinese cabbage could occur within 0.25 h after self-pollination. The hypothetical interaction relationships indicated that plastid-lipid-associated protein and malate dehydrogenase could be negatively regulated by chaperonin 10, glutathione transferase, cytidylate kinase/uridylate kinase, and methionine synthase by indirect interactions. Our findings could be helpful to better understand potential roles of these components in the SI system of non-heading Chinese cabbage.


Assuntos
Brassica/genética , Regulação da Expressão Gênica de Plantas , Glicoproteínas/genética , Proteínas de Plantas/genética , Polinização/genética , Proteínas Quinases/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Brassica/classificação , Brassica/metabolismo , Chaperonina 10/genética , Chaperonina 10/metabolismo , Flores/genética , Redes Reguladoras de Genes , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Glicoproteínas/metabolismo , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Núcleosídeo-Fosfato Quinase/genética , Núcleosídeo-Fosfato Quinase/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Pólen/genética , Proteínas Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
Br Poult Sci ; 55(3): 335-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24641587

RESUMO

1. This study was conducted to determine the effects of different dietary fat sources on growth performance, tibia fatty acids and biomarkers of bone metabolism in broilers. 2. One-d-old commercial Arbor Acres broilers were fed with a maize-soya bean basal diet for 42 d, supplemented with oils according to the following 5 treatments: lard (lard group); linseed oil (linseed oil group); palm oil (palm oil group); linseed oil + palm oil (60:40 or 40:60 w/w, LP-1 group and LP-2 group, respectively). 3. No significant differences in weight gain, feed intake and gain/feed ratio were observed between the lard and linseed oil groups. Birds fed on palm oil had significantly greater weight gain and feed intake than those fed on lard or linseed oil. Growth performance in LP-1 and LP-2 was significantly greater than that of single-oil groups. 4. Tibia growth and bone characteristics were not influenced by supplementation with lard, linseed oil, or palm oil alone, but broilers fed on a mixture of fats had significantly greater tibia weight and length compared to broilers fed on linseed oil. Bone mineral density in tibia was significantly increased in LP-1 and LP-2 groups. 5. Supplementation of linseed oil alone or in combination with palm oil enhanced apparent digestibility of calcium, reduced serum calcium and increased tibia calcium concentrations. Moreover, supplementation with linseed oil alone or in combination with palm oil had a positive effect on biomarkers of bone growth. 6. The combination of linseed and palm oils was beneficial for growth performance, tibia growth and biomarkers of bone metabolism.


Assuntos
Galinhas/crescimento & desenvolvimento , Óleo de Semente do Linho/farmacologia , Óleos de Plantas/farmacologia , Ração Animal , Animais , Biomarcadores/metabolismo , Peso Corporal , Densidade Óssea/efeitos dos fármacos , Suplementos Nutricionais , Óleo de Palmeira , Tíbia/metabolismo , Tíbia/fisiologia
8.
Transplant Proc ; 45(10): 3546-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24314955

RESUMO

OBJECTIVES: Renal ischemia and reperfusion (I/R) injury frequently leads to acute renal failure (ARF) and multiple-organ injury with a substantial morbidity rate. The primary cause of ARF-associated death is, however, cardiac failure instead of renal failure itself, and the pathogenesis of renal I/R-induced cardiac injury is still poorly understood. We evaluated the efficacy of curcumin pretreatment on cardioprotection. METHODS: Thirty Sprague-Dawley rats were evenly divided into 3 groups of sham-operated control, renal I/R injury, and a curcumin pretreatment group. Renal ischemia was conducted by bilateral occlusions of pedicles for 45 minutes, followed by 3 hours of reperfusion. The cardiac function was assessed by the left ventricular end-systolic-pressure-volume-relation (ESPVR), systolic pressure (SP), ejection fraction (EF), and stroke volume (SV). Myocardial injury was assessed based on creatine kinase muscle brain fraction (CK-MB) and Troponin I (cTnI), and kidney injury was assessed based on blood urea nitrogen (BUN) and creatinine. We also assessed the levels of tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) in the heart tissues. RESULTS: SV, EF, and SP reduced moderately during the ischemic phase with no major change in ESPVR. During reperfusion, SV, SP, and ESPVR initially increased, and then steadily decreased. Myocardial and kidney injury were marked by the increases in serum CK-MB and cTnI, and creatinine and BUN level. Curcumin pretreatment ameliorated ESPVR and attenuated injuries of both the heart and kidney resulting from I/R insult. CONCLUSIONS: Curcumin pretreatment improved cardiac contractility and attenuated myocardial and renal injury through reducing inflammatory response in the kidney and heart and oxidative stress in the myocardium.


Assuntos
Injúria Renal Aguda/prevenção & controle , Curcumina/farmacologia , Cardiopatias/prevenção & controle , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/fisiopatologia , Animais , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Creatina Quinase Forma MB/sangue , Creatinina/sangue , Citoproteção , Modelos Animais de Doenças , Coração/fisiopatologia , Cardiopatias/sangue , Cardiopatias/fisiopatologia , Mediadores da Inflamação/metabolismo , Rim/irrigação sanguínea , Rim/metabolismo , Malondialdeído/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Troponina I/sangue , Fator de Necrose Tumoral alfa/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos
9.
J Appl Microbiol ; 114(6): 1582-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23480628

RESUMO

AIMS: To determine the effects of Lactobacillus fermentum I5007 on the redox state of piglets oxidatively stressed with diquat. METHODS AND RESULTS: Twenty-four, 28-day-old barrows were used in a 2 × 2 factorial design experiment with the main effects being Lact. fermentum supplementation and diquat challenge. Half of the pigs (n = 12) were orally administered with 20 ml of a solution containing 10(8 ) CFU ml(-1) of Lact. fermentum each morning of the 21-day trial, while the remainder received saline. On day 8, these two groups were further subdivided so that half of the pigs in each group (n = 6) were intraperitoneally injected with 10 mg kg(-1) BW diquat, while the remainder received saline. The diquat-injected pigs had significantly poorer performance and increased levels of plasma cortisol, adrenaline, carbonyl and malondialdehyde. Lactobacillus fermentum supplementation significantly increased superoxide dismutase and glutathione and increased the ability to inhibit superoxide anion production in liver and muscle. CONCLUSIONS: Lactobacillus fermentum improved the anti-oxidative defence system and alleviated damage caused by diquat. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus fermentum has the potential to alleviate oxidative stress and improve weaning pig performance.


Assuntos
Diquat/toxicidade , Herbicidas/toxicidade , Limosilactobacillus fermentum , Estresse Oxidativo , Animais , Suplementos Nutricionais , Fígado/metabolismo , Malondialdeído/metabolismo , Músculos/metabolismo , Oxirredução , Superóxido Dismutase/metabolismo , Suínos , Desmame
10.
Genet Mol Res ; 11(1): 112-20, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22290471

RESUMO

Pinellia ternata is an important traditional Chinese medicinal plant. Its different populations in China have various ploidy levels, based on x = 13, as well as extensive aneuploid series. The microsporogenesis process was observed in specimens from three populations from three regions of Hubei Province; they were characterized by normal and abnormal meiotic divisions in pollen mother cells (PMCs) at all stages simultaneously. Meiotic abnormalities including univalents/multivalents, chromosomal laggards/bridges and micronuclei appeared in about 50% of the PMCs, together with abnormal cytokinesis. Chromatin/chromosome transfer between meiocytes occurred only during the first division, at low frequency; this might contribute to these meiotic abnormalities. Although the remaining 50% of the PMCs presented normal cytological behavior, pollen fertility was only about 2%. These results provide cytological explanations for its low seed-set and the general use of asexual reproduction through tubers and bulbils; it also explains the wide variations in chromosome number.


Assuntos
Aberrações Cromossômicas , Cromossomos de Plantas/genética , Meiose , Pinellia/genética , Poliploidia , China , Citocinese , Medicina Tradicional Chinesa , Infertilidade das Plantas , Plantas Medicinais/genética , Pólen/genética
11.
Genet Mol Res ; 11(1): 121-30, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22290472

RESUMO

Houttuynia cordata (Saururaceae) is a leaf vegetable and a medicinal herb througout much of Asia. Cytomixis and meiotic abnormalities during microsporogenesis were found in two populations of H. cordata with different ploidy levels (2n = 38, 96). Cytomixis occurred in pollen mother cells during meiosis at high frequencies and with variable degrees of chromatin/chromosome transfer. Meiotic abnormalities, such as chromosome laggards, asymmetric segregation and polyads, also prevailed in pollen mother cells at metaphase of the first division and later stages. They were caused by cytomixis and resulted in very low pollen viability and male sterility. Pollen mother cells from the population with 2n = 38 showed only simultaneous cytokinesis, but most pollen mother cells from the population with 2n = 96 showed successive cytokinesis; a minority underwent simultaneous cytokinesis. Cytomixis and irregular meiotic divisions appear to be the origin of the intraspecific polyploidy in this species, which has large variations in chromosome numbers.


Assuntos
Aberrações Cromossômicas , Cromossomos de Plantas/genética , Gametogênese Vegetal/genética , Variação Genética , Houttuynia/genética , Infertilidade das Plantas , Cromatina/genética , Segregação de Cromossomos/genética , Citocinese/genética , Meiose/genética , Plantas Medicinais/genética , Ploidias , Pólen/genética
12.
Curr Med Chem ; 19(7): 1021-35, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22229417

RESUMO

Methionine aminopeptidases (MetAPs), which remove methionine residue from newly synthesized polypeptide chains, are a class of metalloproteases ubiquitously distributed in both eukaryotes and prokaryotes. MetAP-2 inhibition can induce G1 cell cycle arrest, cytostasis in tumor cells in vitro and inhibition of tumor growth in vivo. The discovery of fumagillin with potent antiangiogenic and antiproliferative activities promoted the development of fumagillin analogues as a novel class of anticancer agents. Early drug discovery efforts have focused on analogs of fumagillin, which irreversibly inhibit MetAP-2 through covalent modification of an epoxide. Several fumagillin analogs, like CKD-732, TNP-470 and PPI-2458, were found to be potent selective inhibitors of MetAP-2 (proteolytic activity) and endothelial cell proliferation. Further, they have entered in clinical trials for the treatment of different types of tumors. Recently, attention has been paid to reversible human MetAP-2 inhibitors, such as bengamides, 2-hydroxy-3-aminoamides, anthranilic acid sulfonamides and triazole analogs, which have demonstrated their potential to inhibit angiogenesis and tumor growth in vivo as well. This review article mainly discussed the development of MetAP-2 inhibitors in cancer therapy and also summarized their structure-activity relationships.


Assuntos
Aminopeptidases/antagonistas & inibidores , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Metaloendopeptidases/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Aminopeptidases/metabolismo , Cicloexanos/química , Cicloexanos/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/metabolismo , Humanos , Metaloendopeptidases/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Relação Estrutura-Atividade
13.
Cell Death Dis ; 2: e185, 2011 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-21796157

RESUMO

The use of celecoxib is associated with a significant decrease in breast cancer risk. However, the long-term use of high-dose celecoxib might be limited owing to cardiovascular side effects. In this study, we found that acetylbritannilactone (ABL), extract from a Chinese medicinal herb, could reduce celecoxib dose and potentiate the growth-inhibitory effect in breast cancer cells. ABL enhanced the apoptotic effect of celecoxib in COX-2-expressing cells, but had little effect in COX-2-negative cells. The apoptosis induced by the combination treatment disappeared when COX-2 was knocked down, whereas the lack of apoptotic effects in COX-2-negative cells was reversed after COX-2 transfection. However, the combination treatment induced a G(0)/G(1) phase arrest independent of whether or not the cells expressed COX-2. The G(0)/G(1) arrest was attributed to a decreased expression of cyclinD1, cyclinE, CDK2 and CDK6, especially the upregulation of p21. In addition, inhibition of Akt and p38 signaling pathways was required by the synergism, as the constitutively active Akt and p38 protected cells against apoptosis and cell cycle arrest induced by the combination treatment. In vivo, administration of celecoxib and ABL were more effective than the individual agents against xenograft tumor growth. Thus, our data suggested that the combinatorial approach of celecoxib and ABL might be helpful for breast cancer treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/toxicidade , Ciclo-Oxigenase 2/metabolismo , Medicamentos de Ervas Chinesas/toxicidade , Lactonas/toxicidade , Pirazóis/toxicidade , Sulfonamidas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Celecoxib , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Fase G1 , Humanos , Lactonas/uso terapêutico , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/uso terapêutico , Fase de Repouso do Ciclo Celular , Transdução de Sinais , Sulfonamidas/uso terapêutico , Transplante Heterólogo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Br J Anaesth ; 106(4): 590-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21307008

RESUMO

BACKGROUND: Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1α, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1α expression and acute lung injury in LPS-treated mice. METHODS: A series of both positive and negative control experiments were performed. We injected BALB/C mice with propofol or vehicle i.p. immediately and 12 h after an LPS challenge. After 24 h, we examined the lung wet/dry weight ratio, neutrophil infiltration, and HIF-1α mRNA expression and inflammatory cytokines in the lung tissue. Survival was determined for 48 h after LPS injection. In vitro, we determined the responses of A549 cells, with and without HIF-1α silenced, to treatment with LPS alone and LPS plus propofol. RESULTS: Propofol prolonged survival and attenuated acute lung injury and decreased the expression of HIF-1α, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-α) in the lungs of endotoxaemic mice. In HIF-1α knockdown-A549 cells, LPS-induced TNF-α, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor κB, reduced HIF-1α expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-α, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and apoptosis. CONCLUSIONS: Propofol reduces apoptosis in LPS-stimulated lung epithelial cells by decreasing HIF-1α, BNIP3, and cytokine production. Using propofol to inhibit HIF-1α expression may protect against the acute lung injury caused by LPS-induced sepsis.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anestésicos Intravenosos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Propofol/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Anestésicos Intravenosos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Citocinas/biossíntese , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Endotoxemia/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Lipopolissacarídeos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Propofol/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
15.
J Anim Sci ; 89(7): 2017-30, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21169511

RESUMO

L-Glutamine (Gln) has traditionally not been considered a nutrient needed in diets for livestock species or even mentioned in classic animal nutrition textbooks. This is due to previous technical difficulties in Gln analysis and the unsubstantiated assumption that animals can synthesize sufficient amounts of Gln to meet their needs. Consequently, the current (1998) version of NRC does not recommend dietary Gln requirements for swine. This lack of knowledge about Gln nutrition has contributed to suboptimal efficiency of global pig production. Because of recent advances in research, Gln is now known to be an abundant AA in physiological fluids and proteins and a key regulator of gene expression. Additionally, Gln can regulate cell signaling via the mammalian target of rapamycin pathway, adenosine monophosphate-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and nitric oxide. The exquisite integration of Gln-dependent regulatory networks has profound effects on cell proliferation, differentiation, migration, metabolism, homeostasis, survival, and function. As a result of translating basic research into practice, dietary supplementation with 1% Gln maintains gut health and prevents intestinal dysfunction in low-birth-weight or early-weaned piglets while increasing their growth performance and survival. In addition, supplementing 1% Gln to a corn- and soybean-meal-based diet between d 90 and 114 of gestation ameliorates fetal growth retardation in gilts and reduces preweaning mortality of piglets. Furthermore, dietary supplementation with 1% Gln enhances milk production by lactating sows. Thus, adequate amounts of dietary Gln, a major nutrient, are necessary to support the maximum growth, development, and production performance of swine.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Dieta/veterinária , Glutamina/metabolismo , Suínos/crescimento & desenvolvimento , Ração Animal , Animais , Suplementos Nutricionais , Feminino , Glutamina/sangue , Glutamina/farmacologia , Lactação , Gravidez , Suínos/sangue
16.
J Anim Sci ; 88(8): 2657-64, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20418458

RESUMO

Piglets obtaining milk from anterior and middle mammary glands (MG) grow faster than those suckling posterior MG, but the underlying mechanisms are not clear. The purpose of this study was to investigate the differential proteomes of colostrum and milk secreted by anterior and posterior MG. Six healthy primiparous sows with 7 pairs of MG were used; the first and the second pairs were defined as anterior MG and the sixth and seventh pairs as posterior MG. Colostrum and milk were collected at d 1 and 14 after parturition, respectively. Comparative proteomics analysis was performed to identify the differentially expressed proteins in colostrum and milk secreted by anterior and posterior MG. Results show that protein composition in colostrum and milk varied markedly with the anatomical location of MG. Immunoglobulins, lactadherin, and haptoglobin were upregulated (P < 0.05) in colostrum from anterior MG compared with posterior MG. Concentrations of immunoglobulins and lactoferrin in milk from anterior MG were greater (P < 0.05) than milk from posterior MG. Moreover, concentration of proteins from somatic cells was greater (P < 0.05) in milk from posterior MG compared with anterior MG. Most proteins, in which abundance was upregulated in colostrum and milk from anterior MG, contribute to passive immunity, intestinal development of suckling piglets and epithelial integrity, and the health of MG. Collectively, these results indicate that in comparison with posterior MG, anterior MG are more active in protein synthesis and produce more immunoglobulins and lactoferrin in colostrum and milk.


Assuntos
Colostro/química , Glândulas Mamárias Animais/fisiologia , Proteínas do Leite/análise , Leite/química , Proteoma/química , Animais , Animais Lactentes/crescimento & desenvolvimento , Western Blotting/veterinária , Eletroforese em Gel Bidimensional/veterinária , Feminino , Espectrometria de Massas/veterinária , Suínos/metabolismo
17.
Poult Sci ; 87(10): 1980-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18809859

RESUMO

Two Leu residues and their ambient amino acid residues are known to exist in the cytosolic tail of chicken invariant chain (Ii), and these play an important role as motifs in mediating the sorting endocytic pathway. We performed 20 mutations via site-directed mutagenesis by the PCR megaprimer method to study the effect of some ambient amino residues of both Leu on the localization of chicken Ii. These mutated fragments were ligated to the vector pEGFP-C1. The recombinant plasmids were transiently transfected into COS-7 cells with Lipofectamine 2000. Furthermore, the fluorescence of located fusion proteins (green fluorescent protein-Ii) was observed with a fluorescence microscope. Our results indicated that 2 Leu-based motifs are required for chicken Ii intracellular localization, and both motifs independently mediate this function of the Ii. The other amino acid residues surrounding both Leu also influence Ii-induced endosomal vacuolation. In addition, we found that Pro19, which is near the Val17-Leu18 motif, was a key residue for chicken Ii intracellular localization. Not only is it critical for endocytic targeting to each Leu, but its unique mutation can also result in altering the function of chicken Ii.


Assuntos
Antígenos de Diferenciação de Linfócitos B/genética , Galinhas/genética , Galinhas/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Leucina , Sequência de Aminoácidos , Aminoácidos/análise , Animais , Células COS , Chlorocebus aethiops , Primers do DNA , DNA Complementar/genética , Haplorrinos , Rim , Transfecção
18.
Peptides ; 28(2): 447-52, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17241697

RESUMO

The expression of neuropeptide Y (NPY) and its co-messenger, agouti-related peptide (AgRP), in arcuate neurons of the hypothalamus is increased during lactation in rats. Our research has been addressing the questions of the physiological actions of these peptides during lactation and the physiological signals associated with lactation that result in increased expression of their genes. Our studies indicate that NPY and AgRP exert pleiotropic actions during lactation that help integrate neuroendocrine regulation of energy balance with controls over anterior and posterior pituitary hormone secretion. Further, reciprocal signaling to the NPY/AgRP system by leptin and ghrelin is responsible for the changes in expression of these hypothalamic peptides in lactating animals, and thus, may contribute to regulation of food intake and the various neuroendocrine adaptations of lactation.


Assuntos
Hipotálamo/fisiologia , Lactação/fisiologia , Neuropeptídeo Y/fisiologia , Proteína Relacionada com Agouti , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia
19.
Poult Sci ; 84(6): 858-64, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15971521

RESUMO

Day-old male broiler chicks were randomly assigned to 32 floor pens in a completely randomized block design and grown to 6 wk of age. Birds in experiment 1 were fed 1 of 2 basal diets supplemented with or without a protease containing feed additive, Versazyme (VZ). The 4 treatments were 1) control (C), a corn-soybean meal diet that contained 95% of amino acids recommended by NRC except for threonine and isoleucine; 2) C + 0.1% VZ (wt/wt) (C+) in the starter diet only; 3) high (HP) amino acid diet, a corn-soybean meal diet with 100 to 105% of amino acid recommended by NRC except for threonine and isoleucine; and 4) HP + 0.1% VZ (wt/wt) (HP+) in starter diet only. Supplementing both diets with VZ improved BW and feed conversion ratio (FCR) at 21 d of age and BW at 42 d of age. Cumulative 42-d FCR was only improved in birds fed the HP+ diet. Birds in experiment 2 received the following treatments: 1) HP, 2) HP + 0.1% VZ batch A (wt/wt) (A) in starter diet only, and 3) HP + 0.1% VZ batch B (wt/wt) (B) in starter diet only. Enzyme supplementation improved 22-d BW and FCR. There was no significant difference in BW at 43 d of age. Both A and B improved overall FCR (1.758 and 1.751 vs. 1.79 for A and B vs. HP, respectively). In conclusion, supplementation of starter broiler diets with VZ resulted in improved market growth performance.


Assuntos
Galinhas/crescimento & desenvolvimento , Dieta , Peptídeo Hidrolases/administração & dosagem , Aminoácidos/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bacillus/enzimologia , Peso Corporal , Suplementos Nutricionais , Masculino , Glycine max , Zea mays
20.
Br J Anaesth ; 92(5): 712-5, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15003978

RESUMO

BACKGROUND: A long-acting analgesic may be particularly desirable in patients suffering from long-lasting pain. The aim of the study was to evaluate the antinociceptive effect of a novel nalbuphine preparation and to determine its duration of action. METHODS: The antinociceptive effects of i.m. nalbuphine HCl in saline and nalbuphine base in sesame oil were evaluated in rats. The in vitro drug-releasing profiles of nalbuphine HCl and base in different preparations were also evaluated. RESULTS: We found that i.m. nalbuphine HCl 25, 50 and 100 micromol kg(-1) produced dose-related antinociceptive effects with a duration of action of 1.5, 2 and 3 h, respectively. i.m. nalbuphine base 100, 200 and 400 micromol kg(-1) also produced dose-related antinociceptive effects but with longer durations of action: 27, 49 and 55 h, respectively. In vitro studies demonstrated that nalbuphine base in sesame oil had the slowest drug-releasing profile of the different preparations. CONCLUSIONS: i.m. injection of an oil formulation of nalbuphine base produced a long-lasting antinociceptive effect.


Assuntos
Analgésicos Opioides/farmacologia , Nalbufina/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Química Farmacêutica , Relação Dose-Resposta a Droga , Excipientes , Injeções Intramusculares , Masculino , Nalbufina/administração & dosagem , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Óleo de Gergelim , Cloreto de Sódio
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