RESUMO
Objective: The present study was represented by di-(2-ethylhexyl) phthalate (DEHP), to explore the role of thyroid hormones (THs) disruption in the connection of placenta and neurodevelopmental toxicity. Methods: During fetal mice neural tube closed (pregnancy 9.5 days, E9.5d) to begin synthesis of THs (E15.5 d), all pregnant mice were administered with different concentration of DEHP (0ã10ã50ã200 mg/kg) by gavage once a day(10 mice per group). All pregnant mice were conducted with BrdU administration in E14d by subcutaneous injection. Seven pregnant mice from each group were scarified after anesthesia in E15.5 d, serum and amniotic fluid were collected to determinate the levels of THs(T(3), T(4), FT(3) and FT(4)) by the automatic biochemical analyzer, detecting fetal mice placental protein expression of monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptide 1C1 (OATP1C1) and deiodinaseâ ¡&â ¢ (DIO(2), DIO(3)) by Western blot. Each group of the remaining three pregnant mices were killed after anesthesia in E18d, take the male fetal brain, BrdU immunohistochemistry was used to detect the proliferation and migration of fetal brain cortical neurons. Results: There was no abnormalities in diet, water intake, body weight and general activity of pregnant mice in each treatment group, and there were no difference in the general physiolo. Results There was no abnormalities in diet, water intake, body weight and general activity of pregnant mice in each treatment group, and there were no difference in the general physiological development status of body weight, brain weight, brain body ratio between the mice of each group. There was no statistically significant differences in serum T(3), T(4), FT(3), FT(4) and amniotic fluid FT(4) in pregnant mice of each group (P>0.05), Compared with the control group, the FT(3) levels in the amniotic fluid of the DEHP 50 and 200 mg/kg groups were significantly decreased(P<0.05). Compared with the control group, the placental MCT8 and DIO(2) protein levels of male fetal mice in the DEHP 50 and 200 mg/kg group decreased, and the level of OATP1C1 protein in 200 mg/kg group decreased(P<0.05), and there was no statistically significant difference in DIO(3) protein levels among all groups (P>0.05). Compared with the control group, the number of BrdU positive cells in the cerebral cortex of male mice in DEHP 200 mg/kg group decreased, 56.5% was distributed in VZ-SVZ layer, and the percentage of BrdU positive cells in the IZ layer of 50 mg/kg group increased (P<0.05). Conclusion: DEHP 50, 200 mg/kg may affect the proliferation and migration of neural cells in the developing brain, which may be related to its interference with thyroid hormone by placental transport.
Assuntos
Dietilexilftalato/farmacologia , Transtornos do Neurodesenvolvimento/induzido quimicamente , Placenta/efeitos dos fármacos , Hormônios Placentários , Glândula Tireoide/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Gravidez , Hormônios TireóideosRESUMO
Objective: To investigate the effects of developmental exposure to DEHP on learning and memory of mice. Methods: Male littermates of ICR mice randomly assigned to five experimental groups (n=14 for each condition) on PND4 to receive distilled water, vehicle and 10, 50 and 200 mg/ (kg·d) DEHP from PND5 to PND38 by gavage, weighing and recording body weight of mice. Open field task were conducted on PND 26 and Morris water maze task were begun from PND30 to PND 37 to evaluate spontaneous exploration activity and emotion, spatial learning and memory performance of pubertal mice, respectively. On PND39, all animals were killed and hippocampi were isolated on ice, then total proteins of hippocampus were extracted, followed by determining the expression of PSD95 and synapsin I by western blotting. Results: 200 mg/ (kg·d) DEHP significantly reduced the growth of body weight of mice and the time staying in the central area in open field, prolonged the time searching the hidden platform in Morris water maze (P<0.05) . 50 mg/ (kg·d) DEHP didn't change the growth of body weight and the emotion (P>0.05) , but reduced the percent of time and distance in the target quadrant during the probe trial of mice in Morris water maze (P<0.05) . The results of western blotting showed that DEHP significantly reduced the expression of PSD95 in hippocampus of mice with all dose groups (P<0.01) , but only 200 mg/ (kg·d) DEHP reduced the expression of synapsin I (P<0.05) . Conclusion: Developmental exposure to DEHP can damage the development of synapse in hippocampus, adversely impacting spatial memory performance of mice at a dose that are insufficient to significantly influence the general development and result in anxiety.
Assuntos
Dietilexilftalato/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Ansiedade , Dietilexilftalato/administração & dosagem , Hipocampo , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Acoustic metamaterials offer great flexibility for manipulating sound waves and promise unprecedented functionality, ranging from transformation acoustics, super-resolution imaging to acoustic cloaking. However, the design of acoustic metamaterials with exciting functionality remains challenging with traditional approaches using classic acoustic elements such as Helmholtz resonators and membranes. Here we demonstrate an ultraslow-fluid-like particle with intense artificial Mie resonances for low-frequency airborne sound. Eigenstate analysis and effective parameter retrieval show two individual negative bands in the single-size unit cell, one of which exhibits a negative bulk modulus supported by the monopolar Mie resonance, whereas the other exhibits a negative mass density induced by the dipolar Mie resonance. The unique single-negative nature is used to develop an ultra-sparse subwavelength metasurface with high reflectance for low-frequency sound. We demonstrate a 0.15λ-thick, 15%-filling ratio metasurface with an insertion loss over 93.4%. The designed Mie resonators provide diverse routes to construct novel acoustic devices with versatile applications.
RESUMO
Objective: To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons. Methods: HT22 cell line were used to, treating with lambda-cyhalothrin (LCT, 50 µmol/L) , 17ß-Estradiol (E2, 10 nmol/L) , LCT (50 µmol/L) +TrkB FC (20 µg/ml) , E2 (10 nmol/L) +TrkB FC (20 µg/ml) , LCT (50 µmol/L) +ICI182 780 (1 µmol/L) , E2 (10 nmol/L) + ICI182 780 (1 µmol/L) , LCT (50 µmol/L) +E2 (10 nmol/L) for 24 h. MTT kit was used to detect cell viability. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell. Results: Campared to Sham, LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF (P<0.05) , campared to LCT, LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF (P<0.05) , campared to E2, E2+TrkB FC could reduce the expression of PSD95 and E2+ICI could reduce the expression of BDNF (P<0.05) , campared to E2, LCT+ E2 could reduce the expression of PSD95 and BDNF (P<0.05) . Conclusion: BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells. Although LCT alone has a similar effect on E2. LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estradiol/farmacologia , Hipocampo/efeitos dos fármacos , Nitrilas/toxicidade , Piretrinas/toxicidade , Linhagem Celular , Estrogênios , Neurônios , Densidade Pós-Sináptica/metabolismoRESUMO
Intervertebral disk disease is a common clinical disorder manifested by pain, ataxia, paresis, motor paralysis, and sensorimotor paralysis. The clinical features, diagnosis, and treatment of cervical and thoracolumbar disk disease have been unclear until now. In this study, some differentially expressed genes were identified, and a network was constructed based on these genes. Through the statistical analysis of nodes and the contrast of 2 more connectivity nodes, it was found that the nodes in the network are in an important position and play key roles. Several of these genes, including MAP2K6, MAP2K3, and MAPK14, belong to the MAP kinase family, and several genes, including RHOBTB2, RHOQ, and RHOH, belong to the RHO family. Therefore, we hypothesize that the development of intervertebral disk disease is related to MAP and RHO family proteins.
Assuntos
Perfilação da Expressão Gênica , Degeneração do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/genética , Disco Intervertebral/metabolismo , Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Anotação de Sequência MolecularRESUMO
BACKGROUND: Iliac bone graft harvesting is a common procedure in spinal surgery and trauma center for spinal fusion and nonunion of the extremities. AIM, PATIENTS AND METHODS: To compare the pain and cosmetic outcomes of patients undergoing iliac crest anatomical reconstruction using equivalent iliac crest allograft (R group) with those of patients without reconstruction of the iliac crest defect (NR group), a prospective nonrandomized controlled study was conducted. RESULTS: In R group, the intensity and prevalence of pain were significantly lower than those in NR group. Cosmetic outcome and satisfaction score were also significantly improved in R group. One patient of R group suffered from lipolysis and superficial infection which healed by regular dressing change for two weeks. There were no cases of allograft displacement, implant loosening, internal fixation breakage or immunological rejection. Seven patients in NR group had significant pain related to the tenting of skin over the defect. Radiologic incorporation of pelvis was documented in all patients except four having partial re-sorption of the allograft. Early fibrous healing and the late creeping substitution were noted in all patients of R group. CONCLUSIONS: Equivalent iliac crest allograft provides an effective alternative for iliac crest anatomical reconstruction, leading to reduced donor site pain and better cosmesis.
Assuntos
Ílio/anatomia & histologia , Ílio/transplante , Sítio Doador de Transplante/anatomia & histologia , Adolescente , Adulto , Transplante Ósseo/efeitos adversos , Avaliação da Deficiência , Feminino , Humanos , Ílio/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Radiografia , Fusão Vertebral , Sítio Doador de Transplante/diagnóstico por imagem , Resultado do TratamentoRESUMO
This study investigates the temperature-tuned band gaps of Lamb waves in a one-dimensional phononic-crystal plate, which is formed by alternating strips of ferroelectric ceramic Ba(0.7)Sr(0.3)TiO(3) and epoxy. The sensitive and continuous temperature-tunability of Lamb wave band gaps is demonstrated using the analyses of the band structures and the transmission spectra. The width and position of Lamb wave band gaps shift prominently with variation of temperature in the range of 26 °C-50 °C. For example, the width of the second band gap increases from 0.066 to 0.111 MHz as the temperature is increased from 26 °C to 50 °C. The strong shift promises that the structure could be suitable for temperature-tuned multi-frequency Lamb wave filters.
Assuntos
Acústica/instrumentação , Compostos de Bário , Cerâmica , Compostos de Epóxi , Som , Estrôncio , Temperatura , Titânio , Cristalização , Módulo de Elasticidade , Desenho de Equipamento , Análise de Elementos Finitos , Modelos Teóricos , Movimento (Física) , Fatores de TempoRESUMO
This study investigates the propagation of Lamb waves in phononic-crystal plates in the form of a sandwich-layered structure. The composite plates are composed of periodic layers bilaterally deposited on both sides of the homogeneous core layer. Using the analyses of the band structures and the transmission spectra, it is revealed that the core layer may induce significant modulations to the lower-order Lamb modes. The modulations are ascribed to the reshaped particle displacement fields of the eigenmodes. Prominently, the core layer made of soft material (rubber) combines the identical eigenmodes of the periodic layers into a pair of asymmetric and symmetric modes in which case the periodic layers vibrate independently. However, the core layer made of hard material (tungsten) or medium hardness material (silicon) couples the periodic layers tightly, in which case the composites vibrate as a whole. In addition, it is found that the phononic band gaps are very sensitive to the thickness of the core layer; this could be indispensable to practical applications such as bandgap tuning.
Assuntos
Acústica/instrumentação , Som , Cristalização , Elasticidade , Desenho de Equipamento , Modelos Teóricos , Movimento (Física) , Processamento de Sinais Assistido por Computador , Fatores de Tempo , VibraçãoRESUMO
BACKGROUND: Chromosome 15q11-13 contains a cluster of imprinted genes essential for normal mammalian neurodevelopment. Deficiencies in paternal or maternal 15q11-13 alleles result in Prader-Willi or Angelman syndromes, respectively, and maternal duplications lead to a distinct condition that often includes autism. Overexpression of maternally expressed imprinted genes is predicted to cause 15q11-13-associated autism, but a link between gene dosage and expression has not been experimentally determined in brain. METHODS: Postmortem brain tissue was obtained from a male with 15q11-13 hexasomy and a female with 15q11-13 tetrasomy. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure 10 15q11-13 transcripts in maternal 15q11-13 duplication, Prader-Willi syndrome, and control brain samples. Southern blot, bisulfite sequencing and fluorescence in situ hybridisation were used to investigate epigenetic mechanisms of gene regulation. RESULTS: Gene expression and DNA methylation correlated with parental gene dosage in the male 15q11-13 duplication sample with severe cognitive impairment and seizures. Strikingly, the female with autism and milder Prader-Willi-like characteristics demonstrated unexpected deficiencies in the paternally expressed transcripts SNRPN, NDN, HBII85, and HBII52 and unchanged levels of maternally expressed UBE3A compared to controls. Paternal expression abnormalities in the female duplication sample were consistent with elevated DNA methylation of the 15q11-13 imprinting control region (ICR). Expression of non-imprinted 15q11-13 GABA receptor subunit genes was significantly reduced specifically in the female 15q11-13 duplication brain without detectable GABRB3 methylation differences. CONCLUSION: Our findings suggest that genetic copy number changes combined with additional genetic or environmental influences on epigenetic mechanisms impact outcome and clinical heterogeneity of 15q11-13 duplication syndromes.
Assuntos
Aneuploidia , Encéfalo/metabolismo , Cromossomos Humanos Par 15/genética , Epigênese Genética , Dosagem de Genes/genética , Adolescente , Adulto , Síndrome de Angelman/genética , Síndrome de Angelman/metabolismo , Metilação de DNA , Feminino , Duplicação Gênica , Expressão Gênica , Humanos , Masculino , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , SíndromeRESUMO
The aim of this study was to compare the protective effects of three traditional Chinese herbal medicines (ligustrazine, kakonein and Panax notoginsenosides) on multiple organs in a rat model of severe acute pancreatitis (SAP) and to explore the underlying mechanisms. The mortality rates in all three treated groups were significantly lower than the control group (P < 0.05). All three herbal medicines significantly alleviated the pathological changes in the pancreas, liver and kidney in SAP rats, induced pancreatic acinar cell apoptosis and effectively prevented the apoptosis of cells in the liver and kidney; however, no obvious lung protection was observed. Panax notoginsenosides showed better pancreatic protection than ligustrazine and kakonein, while kakonein displayed a better role in improving liver and kidney function. The protective effects of ligustrazine were somewhat more comprehensive.
Assuntos
Isoflavonas/farmacologia , Pancreatite/tratamento farmacológico , Pirazinas/farmacologia , Saponinas/farmacologia , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Ginsenosídeos/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Panax/química , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/complicações , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de DoençaRESUMO
The aim of this study was to assess the efficacy and safety of strontium ranelate in the treatment of postmenopausal women with osteoporosis in Taiwan. In this 12-month multicenter, randomized, double-blind, placebo-controlled study, 125 women with osteoporosis were randomly given either strontium ranelate 2 g daily or placebo. Lumbar spine, femoral neck, and total-hip bone mineral density (BMD) and biochemical markers of bone turnover were measured; adverse events and tolerability were recorded and assessed. Subjects treated with strontium ranelate showed significant increases in BMD of 5.9% at the lumbar spine, 2.6% at the femoral neck, and 2.7% at the total hip, while the placebo group exhibited no significant change at 12 months. Serum level of a formation marker (bone-specific alkaline phosphatase) was also significantly increased at 6 and 12 months. Thus, although the sample size and the treatment duration of this study could not show its effect of reducing osteoprotic fractures, strontium ranelate showed bone protection effects by increasing BMD and concentrations of a bone formation marker. Safety assessment revealed adverse events were mild and not significantly different from placebo.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Cálcio/uso terapêutico , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Tiofenos/uso terapêutico , Vitamina D/uso terapêutico , Idoso , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Cálcio/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Taiwan , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Vitamina D/administração & dosagemRESUMO
We have developed a rapid assay for single nucleotide polymorphism (SNP) detection that utilizes electronic circuitry on silicon microchips. The method was validated by the accurate discrimination of blinded DNA samples for the complex quadra-allelic SNP of mannose binding protein. The microchip directed the transport, concentration, and attachment of amplified patient DNA to selected electrodes (test sites) creating an array of DNA samples. Through control of the electric field, the microchip enabled accurate genetic identification of these samples using fluorescently labeled DNA reporter probes. The accuracy of this approach was established by internal controls of dual labeled reporters and by using mismatched sequences in addition to the wild-type and variant reporter sequences to validate the SNP-genotype. The ability to customize this assay for multiple genes has advantages over other existing approaches.
Assuntos
Proteínas de Transporte/genética , Análise de Sequência com Séries de Oligonucleotídeos , Mutação Puntual , Polimorfismo Genético , Semicondutores , Sequência de Bases , Humanos , Immunoblotting , Interleucina-1/genética , Lectinas de Ligação a Manose , Microeletrodos , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Reprodutibilidade dos TestesRESUMO
A study of whether reperfusion accelerates cell death was performed in 35 pig hearts without collateral circulation. In 15 animals, the distal one-third of the left anterior descending coronary artery was occluded for 1 hour followed by 1-, 3-, or 7-hour reperfusion in 5 animals each. As controls, 5 hearts each were examined after 1, 2, 4 and 8 hours of occlusion of the artery without reperfusion. Heart rate and aortic pressure before and during occlusion and reperfusion did not change in any group. The subepicardial and subendocardial regional blood flow decreased to almost zero in all hearts after occlusion (85 +/- 1 to 2 +/- 2) but recovered during reperfusion (65 +/- 15 ml/100 g/min). Specimens were histologically examined by an enzyme method using nitrotetrazolium blue, an immunohistochemical method using myoglobin antibody, by staining with hematoxylin-eosin and Masson's trichrome. In the control hearts, clear demarcation of the infarct area was observed 4 hours after occlusion. However, in the reperfusion group, clear demarcation of the infarct was seen after 1-hour reperfusion, namely, 2 hours after the onset of infarct. Demarcation was seen not only in the tissue with contraction band necrosis, but also in the tissue with coagulation necrosis. Therefore, it is concluded that reperfusion accelerates cell death due to both contraction band necrosis and coagulation necrosis.
Assuntos
Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Animais , Hemodinâmica , Necrose , SuínosRESUMO
BACKGROUND: Multifocal atrial tachycardia (MAT) is a difficult clinical problem generally associated with acute cardiorespiratory illness. The purpose of this study was to assess the feasibility and clinical usefulness of atrioventricular (AV) junction modification as a nonpharmacologic therapy for medically refractory MAT. METHODS AND RESULTS: Thirteen patients with COPD and medically refractory MAT underwent AV junction modification. Complications and outcome of this procedure were monitored. Subjective perceptions of quality of life assessed by a semiquantitative questionnaire and cardiac performance study were obtained before ablation (baseline) and 1 and 6 months after ablation. Radiofrequency energy was applied until the average ventricular rate fell to < 100 beats/min. Ablation procedures controlled the ventricular response in 11 of 13 patients (84%). One patient had unsuccessful modification. Another patient developed delayed complete AV block on the second day after ablation. In these 13 patients, average ventricular rate was reduced from a mean of 145 +/- 11 to 89 +/- 22 beats/min immediately after the ablation (p < 0.01). One patient had recurrent symptomatic MAT at 1 month after ablation; this patient underwent a second procedure without late recurrence. All patients were followed up for at least 6 months (mean, 11 +/- 5 months; range, 6 to 18 months). General quality of life and frequency of significant symptoms improved significantly in patients with successful modification at 1 and 6 months. The left ventricular ejection fraction increased significantly after ablation (44.5 +/- 7.3% at baseline, 49.4 +/- 4. 2% at 1 month, and 50.0 +/- 4.9% at 6 months; all p < 0.05). However, right ventricular ejection fraction remained unchanged (34.7 +/- 6. 2% at baseline, 35.7 +/- 4.4% at 1 month, and 34.3 +/- 4.6% at 6 months; all p > 0.05). The consumption of health-care resources (including frequency of hospital admission and emergency department attendance, antiarrhythmic drug trials) decreased significantly 6 months after AV junction modification. Pulmonary function and theophylline level remained unchanged during follow-up. CONCLUSIONS: AV junction modification offers an effective therapy for controlling ventricular rate in medically refractory MAT. This procedure improves the quality of life and left ventricular function in selected patients with symptomatic and medically refractory MAT.
Assuntos
Nó Atrioventricular/cirurgia , Ablação por Cateter , Pneumopatias Obstrutivas/complicações , Taquicardia Atrial Ectópica/cirurgia , Idoso , Antiarrítmicos/uso terapêutico , Nó Atrioventricular/fisiopatologia , Eletrocardiografia , Estudos de Viabilidade , Feminino , Frequência Cardíaca , Humanos , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória , Estudos Retrospectivos , Inquéritos e Questionários , Taquicardia Atrial Ectópica/complicações , Taquicardia Atrial Ectópica/tratamento farmacológico , Resultado do TratamentoRESUMO
Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (PAssuntos
Anlodipino/uso terapêutico
, Anti-Hipertensivos/uso terapêutico
, Hipertensão/tratamento farmacológico
, Nifedipino/uso terapêutico
, Sudeste Asiático
, Monitorização Ambulatorial da Pressão Arterial
, Relação Dose-Resposta a Droga
, Método Duplo-Cego
, Esquema de Medicação
, Humanos
, Hipertensão/fisiopatologia
RESUMO
In simulated moving-bed (SMB) applications, throughput and desorbent consumption are two key factors that control process cost. For a given adsorbent volume and product purity requirements, throughput and desorbent consumption depend on desorbent composition, column configuration, column length to diameter ratio, and adsorbent particle size. In this study, these design parameters are systematically examined for paclitaxel purification. The results show that if adsorbent particle size, column dimensions and column configuration are fixed, the higher the product purity required, the lower the throughput. If product purity and yield are fixed, the larger the solute migration speed ratio, the higher the throughput, and the lower the desorbent consumption. If total bed volume and product purities are fixed, the longer the separation zones, the higher the throughput, but the higher the desorbent flow-rate. An intermediate configuration gives the minimum desorbent consumption. If there are no limits on pressure drop or zone flow-rate, the larger the column length to diameter ratio, the smaller the adsorbent particle size, the higher the throughput, and the lower the desorbent consumption. If the maximum zone flow-rate is controlled by the pressure drop limit and not by the standing waves requirement, the longer the columns, the lower the zone flow-rates and the lower the throughput. For 150 microns adsorbent particles and a maximum zone flow-rate of 300 ml/min, a design with optimal throughput and desorbent consumption is found for paclitaxel purification.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Cromatografia Líquida/métodos , Paclitaxel/isolamento & purificação , Tamanho da PartículaRESUMO
With coronary arteriography we examined the effect of acetylcholine (ACh) on large and small coronary arteries. ACh (12.5 to 200 micrograms) was injected into the right coronary arteries of 10 pigs during left ventricular pacing. The percentage of narrowing of the epicardial major coronary artery was used as an indicator of the constriction of the large coronary arteries, and the time required for the contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery (blood-flow delay) was used as an indicator of the constriction of the same coronary arteries. A small dose of ACh (12.5 to 100 micrograms) induced mild narrowing (14 to 41%) of the epicardial major coronary artery and a marked blood-flow delay of over 7.0 sec (control: less than or equal to 1.8 sec) in all 10 pigs. A large dose of ACh (100 to 200 micrograms) caused over 75% narrowing of the epicardial major coronary artery and a marked blood-flow delay in 4 of the 10 pigs. When the marked blood-flow delay appeared, the perfused right ventricular myocardium became macroscopically anemic (ischemic). The constriction of large and small coronary arteries was not prevented by diphenhydramine (H1 blocker: 100 mg i.v.), but was prevented by pretreatment with atropine (1.0 mg i.v.). The intracoronary injection of histamine (1.5 mg) in 5 pigs constricted the epicardial major coronary artery over 75% in 2 pigs, 50 to 75% in 1 pig, and 25 to 50% in 2 pigs, but there was no evidence of blood-flow delay. Neither methoxamine nor norepinephrine caused any significant coronary artery narrowing. The histology of the large and small coronary arteries was examined quantitatively with an image analyzer. The coronary artery showed no intimal thickening, and the endothelium was intact on light microscopic examination. The % area of the smooth muscle layer (media) to the calculated total vascular area, and the ratio of the calculated medial thickness to the calculated inner radius (h/Ri) were 64 +/- 7% (mean +/- SD) and 0.69 +/- 0.16, respectively, in the small coronary arteries less than 100 microns in external diameter, 47 +/- 9% and 0.39 +/- 0.12 in the small coronary arteries 100 to 2000 microns in external diameter, and 34 +/- 4% and 0.24 +/- 0.03 in the large right coronary arteries over 2000 microns in external diameter; the % area of the media and the h/Ri showed a negative correlation with the size of the coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Acetilcolina/farmacologia , Vasos Coronários/efeitos dos fármacos , Acetilcolina/administração & dosagem , Animais , Angiografia Coronária , Vasos Coronários/patologia , Relação Dose-Resposta a Droga , Hemodinâmica , Histamina/administração & dosagem , Histamina/farmacologia , Metoxamina/farmacologia , Norepinefrina/administração & dosagem , Norepinefrina/farmacologia , Suínos , Fatores de Tempo , Vasoconstrição/efeitos dos fármacosRESUMO
In an attempt to define the metabolic abnormalities of the ischemic myocardium, the changes in high energy phosphates, inorganic phosphate and intracellular pH were serially and quantitatively evaluated in ischemic porcine hearts having no collateral circulation, using arterial pressure and respiration gated in vivo 31P magnetic resonance spectroscopy. The protocol was also modified for propranolol pretreatment (0.6 mg/kg intravenously) to define its effect on the metabolism of ischemic myocardium. In the non-treated group, creatine phosphate was rapidly depleted by 10 minutes after ischemia; by 40 minutes, ATP and intracellular pH gradually decreased to 10 +/- 11% of control and to 5.90 +/- 0.26, respectively, and inorganic phosphate rose to 303 +/- 43% of control. In the propranolol treated group, the concentrations of creatine phosphate and ATP were higher, and those of inorganic phosphate and tissue pH were similar compared with controls during 40 minutes of ischemia. This suggests that the beneficial effect of propranolol on the ischemic myocardium is due to the preservation of ATP, an essential energy resource for numerous enzymatic reactions in viable myocardium.
Assuntos
Equilíbrio Ácido-Base/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Doença das Coronárias/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Miocárdio/metabolismo , Propranolol/farmacologia , Respiração/efeitos dos fármacos , Animais , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Fosfatos/metabolismo , Fosfocreatina/metabolismo , SuínosRESUMO
The acceleration of energetic electrons has long been one of the most outstanding problems in astrophysics and space physics, and some recent observations from space satellites show that low-frequency electromagnetic fluctuations in the auroral ionosphere and magnetosphere can often be identified as the kinetic Alfvén modes. A model of nonlinear kinetic Alfvén waves is presented here, in which the effect of electron collisional dissipation has been taken into account. The result is a dissipative solitary kinetic Alfvén wave (DSKAW), which can produce a local shocklike structure with a net electric potential drop and which can thereby accelerate efficiently the electrons to the order of the local Alfvén velocity. Since Alfvénic fluctuation is the most common electromagnetic activity in extensive cosmic plasma environments, the present result suggests that the DSKAW could play an important role in the acceleration and energization of cosmic plasmas.