RESUMO
Reducing the dietary CP concentration in the formulation of low-protein diets without adverse effects on animal growth performance and meat quality remains challenging. In this study, we investigated the effects of nicotinamide (NAM) on the nitrogen excretion, growth performance, and meat quality of growing-finishing pigs fed low-protein diets. To measure the nitrogen balance, we conducted two trials: in nitrogen balance trial 1, four crossbred (Duroc × Landrace × Large White) barrows (40 ± 0.5 kg BW) were used in a 4 × 4 Latin square design with four diets and periods. The diets consisted of a basal diet + 30 mg/kg NAM (a control dose), basal diet + 90 mg/kg NAM, basal diet + 210 mg/kg NAM, and basal diet + 360 mg/kg NAM. In nitrogen balance trial 2, another four barrows (40 ± 0.5 kg BW) were used in a 4 × 4 Latin square design. The diets consisted of a basal diet + including 30 mg/kg NAM (control), basal diet + 360 mg/kg NAM, low-protein diet + 30 mg/kg NAM, and low-protein diet + 360 mg/kg NAM. To measure growth performance, two trials were conducted. In growth performance trial 1, 40 barrows (37.0 ± 1.0 kg) were randomly allocated to one of four dietary treatments (n = 10 per group), whereas in growth performance trial 2, 300 barrows (41.4 ± 2.0 kg) were randomly allocated to one of four dietary treatments, with each dietary treatment conducted in five repetitions with 15 pigs each. The four diets in the two growth performance trials were similar to those in nitrogen balance trial 2. Supplementing the diet with 210 or 360 mg/kg NAM reduced urinary nitrogen excretion and total nitrogen excretion and increased nitrogen retention comparted with the control diet (P < 0.05). Compared with the control diet, the low-protein diet with 360 mg/kg NAM reduced faecal, urinary, and total nitrogen excretion (P < 0.05) without affecting nitrogen retention and average daily gain (P > 0.05). Pigs fed the low-protein diet with 360 mg/kg NAM showed a decreased intramuscular fat content in the longissimus thoracis muscle when compared with pigs fed the control diet (P > 0.05). Our results suggest NAM as a suitable dietary additive to reduce dietary CP concentration, maximise nitrogen retention and growth performance, and decrease fat deposition in pigs.
Assuntos
Niacinamida , Nitrogênio , Suínos , Animais , Niacinamida/farmacologia , Dieta/veterinária , Dieta com Restrição de Proteínas/veterinária , Carne/análise , Ração Animal/análise , Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição AnimalRESUMO
The effectiveness of some common combination of antibiotic growth promoters (AGP) on growth performance, gut health, and meat quality was evaluated during the medication and withdrawal period in broilers. A total of 540 male Arbor Acre broilers at 0 D of age were randomly assigned to 5 treatments, with 6 replicates of 18 chicks. Broilers received diets during the medication period (0 to 42 D) as follows: NC (control diet without AGP), EN (NC + enduracidin 8 ppm + colistin sulfate 8 ppm), BZ (NC + bacitracin zinc 40 ppm + colistin sulfate 8 ppm), CT (NC + chlortetracycline 50 ppm + colistin sulfate 8 ppm), and VG (NC + virginiamycin 20 ppm + colistin sulfate 8 ppm). Broilers were switched to the same finisher diet without AGP during the withdrawal period (43 to 49 D). The feed:gain ratio in EN, BZ, CT, and VG groups were significantly decreased by 0.07, 0.10, 0.06, and 0.05 during 0 to 42 D (P < 0.05), but increased by 0.19 (P > 0.05), 0.33 (P > 0.05), 0.49 (P < 0.05), and 0.69 (P < 0.05) during the withdrawal period, respectively. The jejunum villus height (VH) increased in EN group (P < 0.05) and crypt depth (CD) reduced in BZ, CT, and VG groups (P < 0.05) at 42 D, while jejunum VH increased in EN and BZ groups (P < 0.05) at 49 D compared to NC group (P < 0.05). Meat quality detection at 49 D found all AGP groups with the higher cook loss of the breast muscle, while CT group with the higher cook loss of thigh muscle. Consequently, the overall effects of 4 AGP combinations in the whole period were not significant on growth performance. Their poor growth performance during the withdrawal period should be partly attributed to the falling off a cliff of most digestive enzyme activities from 42 to 49 D. Attention should be paid to the adverse effects of AGP supplementation on meat quality, especially cook loss.
Assuntos
Antibacterianos/metabolismo , Galinhas/fisiologia , Trato Gastrointestinal/efeitos dos fármacos , Substâncias de Crescimento/metabolismo , Sistema Imunitário/efeitos dos fármacos , Carne/análise , Animais , Antibacterianos/administração & dosagem , Trato Gastrointestinal/fisiologia , Substâncias de Crescimento/administração & dosagem , Sistema Imunitário/fisiologia , Masculino , Distribuição AleatóriaRESUMO
Over supplementation of copper (Cu) in animal diets may cause serious pollution in soil, water and harvested crops. To minimize the potential pollution, the effects of corn-soybean basal diet with or without supplementation of 8 mg Cu/kg on laying performance, plasma biochemical metabolic indices, and antioxidant status in laying hens were evaluated under normal and cyclic high temperatures. A total of 240 Hy-Line Brown laying hens were randomly allotted to 4 treatments with 6 replicates of 10 hens per replicate according to factorial design involved in 2 temperatures [normal temperature (NT) vs. cyclic high temperature (CHT)] and 2 dietary Cu addition amount [Cu0 (0 mg/kg) vs. Cu8 (8 mg/kg in the form of CuSO4·5H2O)]. The experimental period included 1-week adaptation, 2-week heat stress and 2-week convalescence. The temperatures of NT groups in the same period or any groups during other periods were kept at 26 ± 2°C except that of CHT groups were 26 ± 2°Câ¼33 ± 2°C cyclically during heat stress period. CHT groups increased (P < 0.05) the rectal temperature and plasma glucose content under heat stress, but decreased (P < 0.01) the egg yield at the second week of heat stress and the first week of convalescence, and the plasma triglyceride, uric acid, and triiodothyronine levels under heat stress. Cu8 groups increased (P < 0.05) egg weight at the first week of convalescence, and plasma thyroxin level during the whole convalescence. Interactions between temperature and Cu content existed (P < 0.05) in the laying rate at the first week of convalescence, and the plasma lactic dehydrogenase level under heat stress. Conclusively, the CHT impaired laying performance. The Cu content (10.3 mg/kg) in corn-soybean basal diet might be sufficient for meeting the maintenance and production requirements of late-phase laying hens, and no Cu supplementation had no adverse effects on egg production and antioxidant indices under cyclic high (26 ± 2°Câ¼33 ± 2°C) or normal (26 ± 2°C) temperatures.
Assuntos
Ração Animal/análise , Antioxidantes/metabolismo , Galinhas/fisiologia , Cobre/metabolismo , Temperatura Alta , Reprodução/efeitos dos fármacos , Animais , Galinhas/sangue , Cobre/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Distribuição AleatóriaRESUMO
This study compared the effects of sodium selenite and selenium yeast and their combination on laying performance, egg quality, antioxidant capacity, and selenium (Se) contents in tissues and eggs. Two-hundred-eighty-eight Jing Hong layers that were similar in laying rate (87.5 ± 0.38%) and body weight (1.70 ± 0.02 kg) were randomly distributed into 4 treatments for 11 wk (from 203 d old to 279 d old) with 9 replicates of 8 hens per replicate. The diets (corn-soybean meal diet) were supplemented with 0 [blank control (BC)], 0.3 mg/kg Se from sodium selenite (SS), 0.15 mg/kg Se from sodium selenite and 0.15 mg/kg Se from Se yeast (SS+SY), or 0.3 mg/kg Se from Se yeast (SY). Results showed that the laying rate of the SS+SY group increased significantly (P < 0.05) compared to the BC and SY groups. There were no differences (P > 0.05) in egg quality between the Se-supplemented diets and the BC diet. The serum glutathione peroxidase (GSH-Px) activity was increased (P < 0.01) in hens fed Se-supplemented diets compared to the BC diet. The liver superoxide dismutase (SOD) activity of the SY group was increased significantly (P < 0.05) compared to the BC group. Significant increase (P < 0.01) due to SY supplementation was noted in the serum vitamin E content compared to BC and SS. Layers fed Se-supplemented diets had higher (P < 0.01) contents of Se in the serum, liver, and kidney compared to the BC diet. Compared to BC, Se content in eggs was significantly increased (P < 0.05) by feeding supplementary Se. In conclusion, the effects of SS and Se yeast were approximately equal in promoting antioxidant capacity of laying hens, while Se yeast is easier to deposit into eggs and tissues. The diet with added equal amounts of the 2 sources of Se was more cost effective and affordable than a comparable amount of Se yeast to obtain the promising production performance and nearly similar Se deposition.
Assuntos
Antioxidantes/metabolismo , Galinhas/fisiologia , Compostos Organosselênicos/metabolismo , Óvulo/fisiologia , Selenito de Sódio/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Feminino , Compostos Organosselênicos/administração & dosagem , Selenito de Sódio/administração & dosagem , Distribuição Tecidual , Leveduras/químicaRESUMO
The aim of this study was to investigate whether maternal dietary supplementations with different zinc (Zn) sources could reduce the deleterious effect of maternal heat stress on hatchability performance and progeny growth performance. A completely randomized design (n = 6) with 2 maternal environmental temperatures [normal 21 ± 1°C (NT) vs. high 32 ± 1°C (HT)] × 3 maternal dietary supplemental Zn levels [Zn-unsupplemented control diet (CON), the control diet + 110 mg of Zn/kg of diet as either inorganic ZnSO4 (iZn) or organic Zn with a moderate chelation strength (oZn)] was used. HT decreased (P < 0.05) fertility, hatchability, chick hatch weight, and embryonic survival. HT also decreased (P ≤ 0.05) progeny BW, ADG, and ADFI at one to 21, 22 to 28, and 29 to 42 d of age as well as breast muscle ratio and plasma aspartate aminotransferase and creatine kinase activities at 42 d of age. Maternal dietary Zn supplementation with either iZn or oZn increased (P < 0.004) Zn contents in yolk and liver, non-weak chick ratio, as well as progeny BW, ADFI, and survivability at one to 21 d of age. Notably, the addition of oZn increased (P < 0.05) hatchability and progeny thigh meat quality by reducing b* value. The progeny ADG at one to 21 d and 22 to 28 d of age and BW at 28 d of age from maternal NT were not affected (P > 0.46) by maternal dietary Zn supplementation, but the above 3 indices from HT-iZn (P < 0.05) and HT-oZn (P < 0.003) were higher than those from HT-CON. Our results indicate that maternal heat stress impairs hatching performance, embryonic development, and progeny growth performance, inducing metabolic changes, while supplementation of Zn in maternal diets regardless of Zn sources improved hatch chick quality and survivability of offspring and alleviated the negative effect of maternal heat stress on growth performance of offspring during the starter period. In addition, maternal dietary supplementation with the organic Zn improved hatchability and progeny meat quality.
Assuntos
Galinhas/fisiologia , Dieta/veterinária , Desenvolvimento Embrionário , Temperatura Alta/efeitos adversos , Reprodução , Zinco/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Embrião de Galinha , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Masculino , Distribuição Aleatória , Reprodução/efeitos dos fármacos , Zinco/administração & dosagemRESUMO
Objective:To explore the method of screening effective antibiotics in active stage of otitis media, in order to lay ground for rational clinical application of antibiotics in this scenario.Method:The clinical data of 198 patients diagnosed as otitis media were analyzed. Based on the results of bacterial culture and drug sensitivity test of middle ear secretion, the clinical availability and the ototoxicity of corresponding drugs, first and second line drugs were screened to control infection. The therapeutic effect of drugs was summarized.Result:In 21 out of 198 cases, there was no growth of common bacteria, while in the remaining 177 cases, there were 36 cases(20.34%) of coagulase negative staphylococcus, which was sensitive to linezolid, vancomycin, cefuroxime, levofloxacin, SMZ-TMP, and rifampin; 30 cases(16.95%) of pseudomonas aeruginosa, which was sensitive to meropenem, imipenem, ceftazidime, amikacin, and piperacillin; and 26 cases(14.69%) of staphylococcus aureus, which was sensitive to linezolid, vancomycin, oxacilin, gentamycin, levofloxacin, ciprofloxacin, moxifloxacin. Drugs that were administrated based on experience including: local use of levofloxacin eardrops, cefuroxime and moxifloxacin as first line oral antibiotics, and ceftazidime as second line oral antibiotics. There were 3 cases of post-operational infection, which recovered after systemic and local use of sensitive drugs and dressing.Conclusion:In otitis media, sensitive antibiotics chosen from results of bacterial culture and drug sensitivity test, are useful in reducing the complication of infection after surgery.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Otite Média Supurativa/tratamento farmacológico , Bacteriemia/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Otite Média Supurativa/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificaçãoRESUMO
To investigate whether supplementing manganese (Mn) to the maternal diet could reduce the deleterious effect of heat stress on the developing embryo, the hatchability, antioxidant status, and expression of heat shock proteins (HSP) were evaluated in chick embryos under normal and high incubation temperatures. A completely randomized design ( = 6) with 2 maternal dietary Mn treatments (unsupplemented control basal diet versus the basal diet + 120 mg Mn/kg as inorganic Mn) × 2 incubation temperatures (normal, 37.8°C, versus high, 39.0°C) was used. High incubation temperature did not affect ( > 0.19) hatchability and embryo mortality and development but did increase ( < 0.05) activities of heart manganese superoxide dismutase (MnSOD) and liver copper zinc superoxide dismutase and liver MnSOD mRNA and protein levels in embryos. High incubation temperature also decreased ( < 0.003) HSP70 protein level in the heart but had no effects ( > 0.07) in the liver of embryos. Maternal diet with Mn supplementation not only increased ( < 0.05) the hatchability and Mn content ( < 0.001) in the yolk and embryonic tissues and the activity of MnSOD in the heart ( < 0.004) as well as relative liver weight ( < 0.05) under normal incubation temperature but also decreased ( ≤ 0.05) embryo mortality and HSP90 mRNA level in the liver and heart of embryos. Furthermore, under high incubation temperature, maternal diet Mn supplementation increased ( < 0.002) MnSOD protein expression in the liver of embryos but had no effect ( > 0.43) under normal incubation temperature. These results indicated that high incubation temperature induced self-protective responses of chick embryos with a modification of antioxidant status and a depression of HSP70 protein level. Maternal dietary supplementation of Mn could improve the hatchability as well as antioxidant ability to protect against heat challenge in embryos during incubation.
Assuntos
Antioxidantes/metabolismo , Embrião de Galinha/fisiologia , Proteínas de Choque Térmico/metabolismo , Temperatura Alta , Manganês/farmacologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Ração Animal/análise , Ração Animal/normas , Animais , Peso Corporal , Embrião de Galinha/metabolismo , Galinhas/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Gema de Ovo/química , Feminino , Temperatura Alta/efeitos adversos , Fígado/embriologia , Fígado/enzimologia , Fígado/metabolismo , Malondialdeído/análise , Manganês/administração & dosagem , Manganês/análise , Miocárdio/enzimologia , Distribuição Aleatória , Superóxido Dismutase/análise , Superóxido Dismutase/genéticaRESUMO
An experiment was conducted to investigate the effects of environmental temperature and dietary Mn on egg production performance, egg quality, and some plasma biochemical traits of broiler breeders. A completely randomized factorial design involved 2 environmental temperatures (a normal temperature, 21 ± 1°C, and a high temperature, 32 ± 1°C) × 3 dietary Mn treatments (a Mn-unsupplemented cornsoybean meal basal diet or the basal diet supplemented with 120 mg of Mn/kg of diet as either MnSO4·H2O or manganese proteinate). There were 6 treatments with 6 replicates (4 birds per replicate). High temperature decreased egg weight (P < 0.0001), laying rate (P < 0.0001), egg yield (P < 0.0001), feed intake (P < 0.0001), egg:feed ratio (P < 0.0001), eggshell strength (P < 0.05) and thickness (P < 0.0001), plasma triiodothyronine level (P < 0.05), and alkaline phosphatase activity (P < 0.04) whereas it increased rectal temperature (P < 0.0001); plasma malondialdehyde level (P < 0.02); and activities (P < 0.002) of lactic dehydrogenase, aspartate aminotransferase, and creatine kinase. Broiler breeders fed the diets supplemented with Mn regardless of source had greater (P < 0.05) eggshell strength and lower (P ≤ 0.05) plasma triiodothyronine level and protein carbonyl content than those fed the control diet. The broiler breeders fed the diet supplemented with the organic Mn had greater (P < 0.01) eggshell thickness than those fed the control diet. There were interactions (P < 0.05) between environmental temperature and dietary Mn in laying rate, egg yield, feed intake, and egg:feed ratio. Under normal temperature, dietary Mn did not affect the above 4 parameters; however, under high temperature, broiler breeders fed the diet supplemented with the organic Mn showed greater (P < 0.03) improvements in these 4 parameters than those fed the control diet. The results from this study indicated that high temperature significantly impaired egg production performance and eggshell quality and induced lipid peroxidation and tissue damage whereas dietary supplementation of either organic or inorganic Mn improved eggshell strength and thermotolerance and reduced protein oxidation and that the organic Mn could alleviate the negative effect of high temperature on egg production performance of broiler breeders at the period of 32 to 45 wk of age.
Assuntos
Galinhas/fisiologia , Suplementos Nutricionais , Ovos/normas , Manganês/farmacologia , Oviposição/efeitos dos fármacos , Temperatura , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Feminino , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Plasma , Carbonilação Proteica , Glycine max/químicaRESUMO
Oxidative injury has been implicated in the aetiology of Parkinson's disease (PD) and gypenosides (GP), which are saponins with various bioactivities, have shown antioxidative effects in vitro. The present study was designed to evaluate the effect of GP on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Acute administration of MPTP led to decreased glutathione content and reduced superoxide dismutase activity in the substantia nigra of the mice, which resulted in oxidative stress, loss of nigral dopaminergic neurons and motor dysfunction. Co-treatment with GP attenuated all the injuries induced by MPTP in a dose-dependent manner. The neuroprotective effect of GP may be attributed to increased antioxidation, as manifested by significantly increased glutathione content and enhanced superoxide dismutase activity in the substantia nigra. These results strongly indicate the possible therapeutic potential of GP as an antioxidant in PD.
Assuntos
Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Substância Negra/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Química Encefálica , Dano ao DNA , Modelos Animais de Doenças , Dopamina/análise , Dopamina/metabolismo , Glutationa/metabolismo , Gynostemma , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Destreza Motora/efeitos dos fármacos , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Extratos Vegetais/farmacologia , Carbonilação Proteica , Teste de Desempenho do Rota-Rod , Substância Negra/patologia , Superóxido Dismutase/metabolismoRESUMO
trans-Resveratrol (resveratrol) has been shown in several studies to significantly modulate biomarkers of bone metabolism. But, there is no direct evidence supporting its inhibitory effect towards bone loss. In the present study, effects of resveratrol on bone mineral density (BMD) and bone calcium content (BCC) were examined in the ovariectomized (OVX) rat model. Female Wistar rats were divided into four groups: SHAM group (sham-operated), OVX group (OVX control), OVX + ALD group (OVX and treated with 1.0 mg/kg of body weight of alendronate sodium), and OVX + RES group (OVX and treated with 0.7 mg/kg of body weight of resveratrol). Tested materials were given by gavage for 12 weeks after ovariectomy. Results showed that rats in the OVX, OVX + ALD, and OVX + RES groups had significantly higher body weights and feed efficiency than those in the SHAM group (P < .01). The OVX group had significantly lower femoral epiphysis BMD than the SHAM group, and epiphysis BMD in the OVX + ALD and OVX + RES groups was significantly greater than that in the OVX group (P < .05). However, the femoral midpoint BMD was not significantly different among the four groups. Additionally, animals in the OVX group had significantly lower BCC compared with the SHAM group, while the BCC of the OVX + ALD and OVX + RES groups was significantly higher than that of the OVX group (P < .05). These results indicated that resveratrol could increase epiphysis BMD and inhibit the decrease of femur BCC in OVX rats, suggesting that it could play a role in protecting against bone loss induced by estrogen deficiency.
Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Fallopia japonica/química , Osteoporose/prevenção & controle , Estilbenos/farmacologia , Absorciometria de Fóton , Alendronato/farmacologia , Alendronato/uso terapêutico , Análise de Variância , Animais , Densidade Óssea/fisiologia , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Distribuição Aleatória , Ratos , Ratos Wistar , Resveratrol , Estilbenos/uso terapêutico , Aumento de Peso/efeitos dos fármacosRESUMO
Interleukin-1-beta (IL-1beta) can promote inflammation by up-regulating vascular adhesion molecules and inhibit inflammation by activating the hypothalamic-pituitary-adrenal (HPA) axis to produce anti-inflammatory glucocorticoids. In this study, chronic morphine was shown to suppress IL-1beta-induction of corticotropin releasing factor (CRF) mRNA and plasma corticosterone levels. Leukocyte-endothelial adhesion (LEA) in rat mesenteric venules increased during IL-1beta- and FMLP-induced inflammation. Chronic morphine potentiated the LEA response to either IL-1beta or FMLP alone, and greatly enhanced LEA in response to combined IL-1beta and FMLP. Thus, it appears that chronic morphine exposure may promote a potentially damaging inflammatory reaction by disrupting the balance between IL-1beta-mediated local inflammation and the anti-inflammatory effects of the HPA axis.
Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Inflamação/metabolismo , Interleucina-1/farmacologia , Morfina/administração & dosagem , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Corticosterona/sangue , Hormônio Liberador da Corticotropina/biossíntese , Hormônio Liberador da Corticotropina/genética , Esquema de Medicação , Sinergismo Farmacológico , Retroalimentação/efeitos dos fármacos , Retroalimentação/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/metabolismo , Inflamação/induzido quimicamente , Injeções Intraventriculares , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Masculino , Mesentério/irrigação sanguínea , Mesentério/citologia , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Sistema Hipófise-Suprarrenal/metabolismo , RNA Mensageiro/biossíntese , Ratos , Vênulas/citologia , Vênulas/efeitos dos fármacosRESUMO
In order to isolate novel genes related to early human embryo development and differentiation, a directional cDNA library was constructed from 3-week-old human embryo. Single-pass DNA sequence analysis was used to sequence 47 randomly picked low-abundance cDNA clones. This approach led us to select a clone, L30, showing significant homology with the telomeric-associated DNA and zinc finger protein genes. It is about 3.8 kb in length and contains an open reading frame of notable length within 5'-region, and a tailing signal of AAUAAA and poly (A+) with 39 A in 3'-region. The gene was transcribed in human embryo by Northern blot hybridization and assigned to human chromosome 12 by in situ hybridization.
Assuntos
DNA Complementar/genética , Proteínas de Ligação a DNA/genética , Telômero/genética , Dedos de Zinco/genética , Clonagem Molecular , Sondas de DNA , Etiquetas de Sequências Expressas , Feminino , Biblioteca Gênica , Humanos , Hibridização In Situ , Análise de Sequência de DNARESUMO
In situ hybridization and Northern blot assay were used to evaluate the effects of exogenous AVP(4-8) on the transcription of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in the adult rat brain. NGF and BDNF expression was found to be significantly enhanced by AVP(4-8) administration in the cerebral cortex and hippocampus, but NT-3 expression was not changed. In the same conditions, behavior-active arginine-vasopressin (AVP) showed a small effect and its behavior-inactive homologue, oxytocin did not. Our results suggest that selective regulation of neurotrophin gene expression by the peptides may be responsible for its memory-enhancing function.
Assuntos
Arginina Vasopressina/análogos & derivados , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Encéfalo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores de Crescimento Neural/biossíntese , Fragmentos de Peptídeos/farmacologia , Animais , Arginina Vasopressina/farmacologia , Northern Blotting , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , DNA Complementar/genética , Hibridização In Situ , Masculino , Fatores de Crescimento Neural/genética , Neurotrofina 3 , Ácido Pirrolidonocarboxílico/análogos & derivados , RNA Antissenso/genética , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Transcrição GênicaRESUMO
Previous alanine scanning mutagenesis of thrombin revealed that substitution of residues W50, K52, E229, and R233 (W60d, K60f, E217, and R221 in chymotrypsinogen numbering) with alanine altered the substrate specificity of thrombin to favor the anticoagulant substrate protein C. Saturation mutagenesis, in which residues W50, K52, E229, and R233 were each substituted with all 19 naturally occurring amino acids, resulted in the identification of a single mutation, E229K, that shifted the substrate specificity of thrombin by 130-fold to favor the activation of the anticoagulant substrate protein C over the procoagulant substrate fibrinogen. E229K thrombin was also less effective in activating platelets (18-fold), was resistant to inhibition by antithrombin III (33-fold and 22-fold in the presence and absence of heparin), and displayed a prolonged half-life in plasma in vitro (26-fold). Thus E229K thrombin displayed an optimal phenotype to function as a potent and specific activator of endogenous protein C and as an anticoagulant in vivo. Upon infusion in Cynomolgus monkeys E229K thrombin caused an anticoagulant effect through the activation of endogenous protein C without coincidentally stimulating fibrinogen clotting and platelet activation as observed with wild-type thrombin. In addition, E229K thrombin displayed enhanced potency in vivo relative to the prototype protein C activator E229A thrombin. This enhanced potency may be attributable to decreased clearance by antithrombin III, the principal physiological inhibitor of thrombin.
Assuntos
Anticoagulantes/farmacologia , Engenharia de Proteínas , Trombina/genética , Trombina/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Fibrinogênio/metabolismo , Meia-Vida , Humanos , Cinética , Macaca fascicularis , Modelos Moleculares , Mutagênese Sítio-Dirigida , Ativação Plaquetária/efeitos dos fármacos , Proteína C/metabolismo , Conformação Proteica , Especificidade por Substrato , Trombina/metabolismoRESUMO
The activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) and free radicals were measured, and the morphological changes were observed in the lens of control rats, selenium-deficient (SeD) and/or vitamin E deficient (VED) rats. The activities of GSH-Px in the lens of SeD rats decreased significantly. The GSH-Px activities of lens were positively related to erythrocytes selenium level. There was a free radical at g = 2.0015 in the rat lens of all groups, but the content of free radicals in the lens of SeD group was significantly higher than that of the control group. The free radical content of lens was negatively related to erythrocytes selenium level, as well as the GSH-Px activities in the lens. In vitro, ultraviolet radiation caused the generation of another kind of free radical (g = 2.0097) in the lens of all groups, but the amount of the free radical in the lens of the SeD group was also significantly higher than that of the control group. The activities of SOD and GSSG-R in VED rat lens were significantly decreased. The amount of MDA in the lens of SeD and/or VED rats were significantly increased. The results showed that the decrease of antioxidative capability in the lenses of SeD and/or VED rats accelerated the lipid peroxidation and generation of free radicals. Although only early morphological changes in SeD and/or VED rat lens were observed, it is considered that selenium and vitamin E deficiency may be involved in the occurrence of cataract.