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1.
Poult Sci ; 99(4): 1914-1920, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241471

RESUMO

In avian species, maternal immunoglobulin Y (IgY) is transferred from the blood to the yolks of maturing oocytes; however, the mechanism underlying this transfer is unknown. To gain insight into the mechanisms of maternal IgY transfer into egg yolks, IgY-depleted chickens were generated by removing the bursa of Fabricius (bursectomy) during egg incubation, and their egg production and IgY transport ability into egg yolks were determined. After hatching, blood IgY concentrations of the bursectomized chickens decreased gradually until sexual maturity, whereas those of IgA remained low from an early stage of growth (from at least 2 wk of age). Chickens identified as depleted in IgY through screening of blood IgY and IgA concentrations were raised to sexual maturity. At 20 wk of age, both blood and egg yolk IgY concentrations in the IgY-depleted group were 600-fold lower than those of the control group, whereas egg production did not differ between the groups. Intravenously injected, digoxigenin-labeled IgY uptake into the egg yolk was approximately 2-fold higher in the IgY-depleted chickens than in the controls, suggesting that IgY depletion may enhance IgY uptake in maturing oocytes. DNA microarray analysis of the germinal disc, including the oocyte nucleus, revealed that the expression levels of 73 genes were upregulated more than 1.5-fold in the IgY-depleted group, although we could not identify a convincing candidate gene for the IgY receptor. In conclusion, we successfully raised IgY-depleted chickens presenting a marked reduction in egg yolk IgY. The enhanced uptake of injected IgY into the egg yolks of the IgY-depleted chickens supports the existence of a selective IgY transport mechanism in maturing oocytes and ovarian follicles in avian species.


Assuntos
Proteínas Aviárias/metabolismo , Galinhas/metabolismo , Gema de Ovo/metabolismo , Imunoglobulinas/metabolismo , Animais , Proteínas Aviárias/deficiência , Bolsa de Fabricius/cirurgia , Galinhas/cirurgia , Feminino , Imunoglobulinas/deficiência
2.
J Bone Joint Surg Br ; 84(4): 518-20, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12043771

RESUMO

The systemic arterial pressure has been used as a guide for determining the susceptibility to surgical bleeding during controlled hypotensive anaesthesia. Arterial hypotension is not, however, necessarily accompanied by venous or intraosseous hypotension. The main source of bleeding during posterior spinal surgery is the bone and is venous rather than arterial. The intraoperative blood loss, the intraosseous pressure (IOP) within the first thoracic vertebral body, and the systemic arterial pressure were measured in 27 patients during cervical laminoplasty for spondylotic myelopathy. The intraoperative blood loss correlated significantly with the vertebral IOP (p = 0.0073, r = 0.499), but not with systemic arterial pressure, age, or body-weight. The systemic arterial pressure did not correlate with the vertebral IOP. The mean value of the mean arterial pressure throughout the operation varied between 74 and 110 mmHg. The findings suggest that the vertebral IOP parallels surgical bleeding during posterior spinal surgery under normotensive anaesthesia and that patients with a low arterial pressure do not necessarily have a low IOP.


Assuntos
Perda Sanguínea Cirúrgica/fisiopatologia , Complicações Intraoperatórias/fisiopatologia , Procedimentos Neurocirúrgicos/efeitos adversos , Coluna Vertebral/fisiopatologia , Coluna Vertebral/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão
3.
J Orthop Sci ; 6(1): 88-91, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11289592

RESUMO

We report a patient with nonoperatively treated acute cauda equina compression arising from an epidural clot that developed after decompressive surgery for lumbar canal stenosis. A 43-year-old woman underwent lumbar laminotomy, and was symptom-free for 3 hours; but this was followed by paresis. Postoperative myelography showed obstruction of the contrast column at the level of the laminotomy; this was relieved by hyperflexion of the lumbar spine. With sustained hyperflexion of the lumbar spine, all neurologic deficits were completely resolved within 5 days. Lumbar lordosis may be present when a patient lies in the supine position on a flat bed with the hips and knees extended; this may exacerbate dural constriction caused by an epidural clot following posterior lumbar spinal surgery.


Assuntos
Hematoma Epidural Craniano/complicações , Postura , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/fisiopatologia , Adulto , Cauda Equina , Feminino , Humanos , Laminectomia , Lordose/complicações , Vértebras Lombares/cirurgia , Mielografia , Complicações Pós-Operatórias , Estenose Espinal/cirurgia
4.
J Orthop Sci ; 5(3): 283-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10982670

RESUMO

Tibial intraosseous pressure and blood flow, along with arterial pressure, were measured in anesthetized rabbits before and during intravenous infusion of prostaglandin E1 at doses of 0, 100, 300, 1000, and 2000 ng/kg per min. The mean arterial pressure decreased dose-dependently. The intra-osseous pressure increased during infusion at doses of 300 and 1000 ng/kg per min, but decreased during infusion at the dose of 2000 ng/kg per min. Bone blood flow increased during infusion only at a dose of 1000 ng/kg per min. Calculated vascular and arteriolar resistances in bone decreased dose-dependently during infusion at doses of up to 1000 ng/kg per min, but no change was seen when the dose was increased from 1000 to 2000 ng/kg per min. These findings indicated that: (1) there was a turning point in the effect of prostaglandin E1 at a certain dose between 1000 and 2000 ng/kg per min, at which the arterioles in bone were fully dilated; (2) at a dose of 1000 ng/kg per min or lower, responsive dilatation in the arterioles of bone under mild arterial hypotension increased the influx of blood into the bone, thereby increasing the intraosseous pressure; and (3) at doses higher than 1000 ng/kg per min, dose-dependent arterial hypotension without further dilatation in the arterioles of bone decreased the influx of blood.


Assuntos
Alprostadil/farmacologia , Perda Sanguínea Cirúrgica/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Osso e Ossos/irrigação sanguínea , Hipotensão Controlada , Ortopedia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Osso e Ossos/cirurgia , Relação Dose-Resposta a Droga , Masculino , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos
5.
J Bacteriol ; 180(16): 4303-8, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9696784

RESUMO

The Clostridium josui cipA and celD genes, encoding a scaffolding-like protein (CipA) and a putative cellulase (CelD), respectively, have been cloned and sequenced. CipA, with an estimated molecular weight of 120,227, consists of an N-terminal signal peptide, a cellulose-binding domain of family III, and six successive cohesin domains. The molecular architecture of C. josui CipA is similar to those of the scaffolding proteins reported so far, such as Clostridium thermocellum CipA, Clostridium cellulovorans CbpA, and Clostridium cellulolyticum CipC, but C. josui CipA is considerably smaller than the other scaffolding proteins. CelD consists of an N-terminal signal peptide, a family 48 catalytic domain of glycosyl hydrolase, and a dockerin domain. N-terminal amino acid sequence analysis of the C. josui cellulosomal proteins indicates that both CipA and CelD are major components of the cellulosome.


Assuntos
Proteínas de Bactérias/genética , Celulase/genética , Clostridium/genética , Proteínas de Membrana/genética , Complexos Multienzimáticos/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Clostridium/enzimologia , Dados de Sequência Molecular , Complexos Multienzimáticos/metabolismo , Homologia de Sequência de Aminoácidos
6.
Int Orthop ; 22(2): 69-76, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9651769

RESUMO

In posterior lumbar interbody vertebral fusion operations, variously sized, rectangular shaped, defatted, freeze-dried, gas-sterilised cortical bone allografts were used in combination with cancellous bone autografts from excised posterior elements. Single-level fusion, with or without internal fixation, was undertaken in 38 patients aged 50 years or less with disc herniation or a failed discectomy (the younger group) and in 33 women aged 60 years or more with degenerative spondylolisthesis (the older group). Of the various observable indicators of union, changes in the allograft-host interface alone proved to be of practical use. The incidence of nonunion in patients managed with pedicle screws, with a hook and rod system or without internal fixation was 0 of 8 patients; 1 of 14 patients; and 3 of 16 patients, respectively, in the younger group, and 0 of 11 patients; 0 of 8 patients; and 2 of 14 patients, respectively, in the older group. Of the six patients with nonunion, three had persistent low back pain and only two had mobility of the fused segment which was evident on lateral radiographs during flexion and extension. No patient had graft collapse. The decrease in the height of the intervertebral space, chiefly due to settlement of the allograft into the vertebral bodies, in the younger and older groups averaged 1.1 and 1.6 mm, respectively. We concluded that this simplified technique is mechanically sound and effective in maintaining the height of the intervertebral space. Even when the graft failed to unite, fibrous union could be obtained without graft collapse. Combination with a simple internal fixator, such as a compression rod, facilitates bone union.


Assuntos
Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Tíbia/transplante , Transplante Homólogo , Adulto , Idoso , Clorofórmio/farmacologia , Óxido de Etileno , Feminino , Liofilização , Humanos , Fixadores Internos , Lipídeos , Masculino , Metanol/farmacologia , Pessoa de Meia-Idade , Esterilização/métodos , Transplante Autólogo , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-10028490

RESUMO

We studied the central nervous system (CNS) effects of 3-[4-(8-fluoro-5, 11-dihydrobenz[b] oxepino[4, 3-b]pyridin-11-ylidene)piperidino]propionic acid dihydrate (HSR-609), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on gross behavior, spontaneous electroencephalograms (EEG) and some pharmacological parameters of unanesthetized, unrestrained dogs with chronic indwelling brain electrodes after oral administration were compared with typical antiallergic agents and 8-fluoro-5, 11-dihydro-11-(1-methyl-4-piperidylidene)benz[b] oxepino[4,3-b]pyridine (PY-608), a non-amphoteric basic compound having a similar chemical structure to HSR-609. HSR-609 (1, 10 and 100 mg/kg) and terfenadine (100 mg/kg) had no effect on the behavior, EEG patterns, sleep-wakefulness cycles or EEG power spectrum. Cyproheptadine (10 mg/kg), ketotifen (30 mg/kg) and PY-608 (10 mg/kg) increased slow waves with high amplitude in all EEG leads and caused dissociation between the slowing of EEG and waking behavior. Both azelastine (30 mg/kg) and oxatomide (100 mg/kg) caused generalized seizure discharges accompanied by agitation with the former and sedation with the latter. These findings suggest that observations of behavior and EEG in conscious dogs can be useful for clarifying the pharmacological characteristics of various antiallergic agents on the CNS. We were able to show that HSR-609 has no effect on the behavior and EEG of dogs because of its amphoteric chemical structure.


Assuntos
Antialérgicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzoxepinas/farmacologia , Eletroencefalografia/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Piridinas/farmacologia , Animais , Ciproeptadina/farmacologia , Cães , Feminino , Cetotifeno/farmacologia , Masculino , Ftalazinas/farmacologia , Piperazinas/farmacologia , Terfenadina/farmacologia
8.
Jpn J Pharmacol ; 75(1): 43-57, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9334885

RESUMO

We studied the central nervous system (CNS) effects of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11- ylidene) piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on the behavior of mice and the electroencephalograms (EEG) of unanesthetized and unrestrained rabbits after oral administration were compared with those of typical antiallergic agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz [b]oxepino[4,3-b]pyridine), which has chemical structure similar to that of HSR-609. HSR-609 (3-300 mg/kg) had no effect on general behavior, spontaneous locomotor activity, hexobarbital-induced sleeping time and reserpine-induced hypothermia in mice. HSR-609 (10-100 mg/kg) and terfenadine (100 mg/kg) had no effect on spontaneous EEG, sleep-wakefulness cycles and EEG power spectra in rabbits. On the other hand, cyproheptadine (3-30 mg/kg), ketotifen (30-100 mg/kg) and PY-608 (0.3-100 mg/kg) caused increases and/or decreases of spontaneous locomotor activity, prolongation of hexobarbital-induced sleeping time and antagonistic effects on reserpine-induced hypothermia in mice. These agents (30 mg/kg) increased slow wave sleep and enhanced EEG power spectra at low frequency bands such as delta and theta in rabbits. These findings suggest that HSR-609 has no inhibitory effect on the CNS due to its amphoteric chemical structure.


Assuntos
Antialérgicos/farmacologia , Benzoxepinas/farmacologia , Piridinas/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hexobarbital/farmacologia , Hipnóticos e Sedativos/farmacologia , Hipotermia/induzido quimicamente , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Periodicidade , Coelhos , Reserpina/farmacologia , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos
9.
J Bone Joint Surg Am ; 79(6): 818-25, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9199377

RESUMO

Direct repair of a defect in the pars interarticularis was performed with use of bone-grafting and internal fixation with a pedicle screw, rod, and laminar hook in order to achieve a higher prevalence of osseous union than that achieved with commonly used procedures. The configuration of the head of the screw, which is designed to allow it to connect with the rod at the necessary angle, simplified the placement of the rod. The procedure was performed in sixteen patients who had a bilateral defect of the pars interarticularis with or without grade-I or II spondylolisthesis, had had failure of non-operative treatment, and had had temporary relief of pain after the area of the defect in the pars interarticularis had been infiltrated with lidocaine. Concomitant degeneration of a disc was not a criterion for exclusion. The patients were followed for an average of twenty-five months (range, twenty-four to twenty-eight months). The average age at the time of the operation was thirty-two years (range, twelve to sixty years). Six patients had findings of nerve-root compression on myelography with computerized tomographic scanning, and the bone spurs overlying the affected nerve root around the defect in the pars interarticularis were removed with an ultrasonic osteotome through a small window. The implant was removed about one year after the operation. Oblique radiographs showed osseous union in the previous defect bilaterally in all sixteen patients. Thirteen patients were free of symptoms, and three had major improvement with occasional low-back pain. None had a complication, such as infection, breakage of the implant, or irritation of a nerve root. The method used for direct repair of the defect of the pars interarticularis in these patients proved to be simple and effective. Relief of symptoms appeared to depend on decompression of the affected nerve root, if one was involved, and on preoperative prediction of the locus of the symptoms by infiltration of the pars interarticularis with lidocaine.


Assuntos
Parafusos Ósseos , Fixadores Internos , Vértebras Lombares/cirurgia , Espondilólise/cirurgia , Adolescente , Adulto , Anestésicos Locais/uso terapêutico , Transplante Ósseo/métodos , Criança , Desenho de Equipamento , Feminino , Seguimentos , Previsões , Humanos , Lidocaína/uso terapêutico , Dor Lombar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mielografia , Síndromes de Compressão Nervosa/etiologia , Osteotomia , Prevalência , Raízes Nervosas Espinhais/patologia , Osteofitose Vertebral/cirurgia , Espondilolistese/classificação , Espondilolistese/complicações , Espondilólise/complicações , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Terapia por Ultrassom , Cicatrização
10.
Jpn J Pharmacol ; 73(4): 291-8, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9165365

RESUMO

We studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11- ylidene)- piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent, on the central nervous system (CNS). Its selectivity for the histamine H1-receptor and its ability to penetrate into the CNS were compared with those of typical antiallergic agents and the nonamphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz[b]oxe pino- [4,3-b]pyridine), which has a chemical structure similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity for H1-receptors in the guinea pig cerebral cortex in comparison to affinities for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while the selectivity of PY-608 for the H1-receptor was low. The inhibitory effects of these antiallergic agents on histamine-induced increase of vascular permeability in mice (ED50) were compared with the displacement of [3H]mepyramine binding to H1-receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was much larger than those of cyproheptadine, ketotifen and PY-608 and larger than those of terfenadine and cetirizine. HSR-609 was found to display selective displacement of the [3H]mepyramine binding to H1-receptors for lung vs cerebral cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest that HSR-609 has high selectivity for the H1-receptor and poor ability to penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical structure.


Assuntos
Antialérgicos/metabolismo , Benzoxepinas/farmacologia , Córtex Cerebral/metabolismo , Antagonistas dos Receptores Histamínicos H1/farmacologia , Piridinas/farmacologia , Receptores Histamínicos H1/efeitos dos fármacos , Administração Oral , Animais , Antialérgicos/farmacologia , Benzoxepinas/administração & dosagem , Benzoxepinas/química , Benzoxepinas/farmacocinética , Ligação Competitiva , Permeabilidade Capilar/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Cobaias , Histamina/toxicidade , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/química , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Técnicas In Vitro , Marcação por Isótopo , Dose Letal Mediana , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Piridinas/administração & dosagem , Piridinas/química , Piridinas/farmacocinética , Pirilamina/metabolismo , Ratos , Receptores Histamínicos H1/metabolismo , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/metabolismo , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Padrões de Referência , Relação Estrutura-Atividade
11.
Spine (Phila Pa 1976) ; 22(8): 889-94, 1997 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-9127923

RESUMO

STUDY DESIGN: This study consisted of a comparison of intraoperative blood loss during posterior spins surgery under normotensive general anesthesia with and without epidural blockade, and a hemodynamic study after epidural injection. OBJECTIVES: To determine the effect of epidural blockade in reducing blood loss and intraosseous pressure in the vertebral body. SUMMARY OF BACKGROUND DATA: Epidural anesthesia is effective in reducing surgical bleeding. This effect has been thought to be due to systemic arterial hypotension. There was no report on its effect on venous pressure or intraosseous pressure. METHODS: In comparison of blood loss epidural blockade was achieved by preincisional caudal epidural injection of 20 ml of 0.25% bupivacaine during cervical laminoplasty or posterior lumbar interbody fusion. For each surgical procedure, there were 20 patients who received epidural blockade and 20 who did not. In a hemodynamic study, intraosseous pressure in the second thoracic or the second or third lumbar vertebral body, intraosseous pressure in the calcaneus, and systemic arterial blood pressure were measured continuously before and after the caudal epidural injection of 20 ml of 1% lidocaine during posterior cervical or lumbar spine surgery in 42 patients. RESULTS: Total and hourly intraoperative blood loss during posterior lumbar interbody fusion was significantly less in the group with blockade than in the group without blockade, but the values during cervical laminoplasty showed no significant difference between the two groups. The lumbar vertebral intraosseous pressure decreased significantly after epidural injection, whereas the second thoracic vertebral and the calcaneal in traosseous pressure did not decrease significantly. The ratio of lumbar vertebral intraosseous pressure to arterial pressure decreased continuously after epidural injection, whereas the ratio of the calcaneal intraosseous pressure to arterial pressure transiently increased. CONCLUSIONS: The epidural blockade reduces intraoperative bleeding, even under normotensive conditions, and it takes effect in the lumbar spine, but not in the upper thoracic or cervical spine. This effect appears to be due chiefly to venous hypotension in the lumbar spine, which may be created by sympathetic blockade, with arteriolar dilatation and venous pooling in the lower limbs and reactive vasoconstriction in the lumbar vertebrae.


Assuntos
Anestesia Epidural , Anestesia Geral , Anestésicos Locais , Perda Sanguínea Cirúrgica/prevenção & controle , Bupivacaína , Vértebras Cervicais/cirurgia , Hemodinâmica/fisiologia , Lidocaína , Vértebras Lombares/cirurgia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fusão Vertebral
12.
Int Orthop ; 21(1): 62-6, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9151189

RESUMO

We report the effect of pre-incisional caudal epidural injection of a mixture of 20 ml 0.25% bupivacaine and 0.1 mg buprenorphine performed under general anaesthesia for relieving wound pain after posterior interbody fusion and laminotomy for spinal stenosis. Pain was compared in groups with and without blockade: 24 and 23 patients with fusion, and 30 and 28 with laminotomy respectively. In the first 12 h after each operation, the group with blockade required additional analgesics less frequently and had a lower visual analogue scale score than those without blockade. In, and after, the second 24 h patients with hypotension of 10 mm Hg, or more, after the blockade required additional analgesics less frequently than those without blockade for both operations and had a lower visual analogue score than those without blockade for laminotomy, but not for fusion. This is a simple procedure for relieving wound pain and in patients with hypotension caused by the block, the effect continued even after the analgesic action had disappeared.


Assuntos
Analgésicos Opioides/uso terapêutico , Anestesia Caudal , Anestésicos Locais/uso terapêutico , Bupivacaína/uso terapêutico , Buprenorfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Estenose Espinal/cirurgia , Adulto , Idoso , Estudos de Avaliação como Assunto , Feminino , Humanos , Injeções Espinhais , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade
13.
Chem Pharm Bull (Tokyo) ; 44(7): 1376-86, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8706143

RESUMO

We previously demonstrated that 5-amino-7-(3-amino-1-pyrrolidinyl) -1-cyclopropyl-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (7) has strong in vitro antibacterial activity even against quinolone-resistant bacteria. We examined optimization of the 3-aminopyrrolidine moiety of 7 by introduction of C-alkyl (Me, Et, Pr, di-Me, cyclopropyl) and N-alkyl groups (Me, di-Me). C-Alkylation at the 4-position of the 3-aminopyrrolidine moiety enhanced in vitro and in vivo antibacterial activity. (S)-5-Amino-7-(7-amino-5-azaspiro[2.4]hept-5-yl)-1-cyclopropyl-pyr rolidinyl) -1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (15b) showed strong antibacterial activity (in vitro antibacterial activity including quinolone-resistant bacteria is 4 times more potent than that of ciprofloxacin (CPFX) (1); in vivo antibacterial activity is 1.5 to 20 times more potent than that of CPFX (1)) and reduced quinolone toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion when coadministered with 4-biphenylacetic acid at a dosage of 20 micrograms in rats (i.c.v.)). Their selectivity between DNA topoisomerase II (derived from eukaryotic cells) and DNA gyrase (derived from bacterial cells) was about 3000-fold.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Animais , Anti-Infecciosos/toxicidade , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas , Cobaias , Klebsiella pneumoniae/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Ratos , Receptores de GABA/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Estereoisomerismo , Inibidores da Topoisomerase II
14.
Chem Pharm Bull (Tokyo) ; 44(5): 1074-85, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8689718

RESUMO

A series of 7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-4- oxoquinoline-3-carboxylic acids bearing various substituents (H, F, C1, Me, OH, OMe, OEt, OCH2F, OCHF2, OCF3, SMe) at the C-8 position was prepared and evaluated for in vitro antibacterial activity against both standard laboratory strains and bacteria resistant to quinolones such as ciprofloxacin (CPFX, 1) and ofloxacin (OFLX, 2) from clinical isolates. The 8-methyl (8a), 8-fluoro (9a), 8-chloro (10a) and 8-methoxy (12a) compounds were 4 times more potent than CPFX (1) against both gram-positive and gram-negative bacteria. But these four compounds caused injury to the chromosomes of mammalian cells at a concentration of 100 micrograms/ml. Next, a series of quinolones having various substituents (H, C1, Me, NH2, NHMe, NMe2) at the C-5 position was prepared and evaluated for antibacterial activity and injurious effect on the chromosome. We found that the 5-amino-8-methyl compound (8d) showed strong antibacterial activity (in vitro antibacterial activity of 8d is 4 times more potent than that of CPFX (1) against both gram-positive and gram-negative bacteria), reduced injury to the chromosome, and reduced quinolone-type toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion-inducing activity when coadministered with fenbufen at dosage of 100 mg/kg in mice (i.p.)).


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , 4-Quinolonas , Animais , Anti-Infecciosos/efeitos adversos , Linhagem Celular , Cricetinae , Cricetulus , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Cobaias , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Testes de Mutagenicidade , Transtornos de Fotossensibilidade/induzido quimicamente , Espectrofotometria Infravermelho , Relação Estrutura-Atividade
15.
Chem Pharm Bull (Tokyo) ; 44(5): 1107-10, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8689720

RESUMO

Fibrinogen-related peptides, monomeric cyclic peptides through a disulfide bond [cyclo(H-Cys-Arg-Gly-Asp-Phe-Cys-NH2), cyclo(H-Cys-Arg-Gly-Asp-Phe-Cys-Gly-NH2), cyclo(H-Cys-Arg-Gly-Asp-Cys-NH2) and cyclo(H-Cys-Arg-Gly-Asp-Cys-Gly-NH2)], were prepared by the solid phase method with disulfide bond formation on the solid support. The acetamidomethyl group was used for protection of the thiol group of Cys and synthetic peptide-resins were treated with iodine to give the disulfide bond. Monomeric cyclic peptides were obtained as main products. Purified S-acetamidomethylated peptides were also oxidized with iodine, but the desired materials could not be isolated by HPLC. The disulfide formation from S-acetamidomethylcysteine-containing peptide resin by iodine treatment on the solid support was more effective than that from S-acetamidomethylcysteine-containing peptide. The inhibitory effect of the cyclic peptides on platelet aggregation were much more potent than that of H-Arg-Gly-Asp-NH2.


Assuntos
Dissulfetos/química , Fibrinogênio/química , Peptídeos Cíclicos/síntese química , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Humanos , Técnicas In Vitro , Espectrometria de Massas , Dados de Sequência Molecular , Peptídeos Cíclicos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia
16.
Int Orthop ; 20(3): 142-6, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8832315

RESUMO

We devised a method of sterilising bone allografts which consists of defatting in chloroform and methanol, freeze-drying and sterilisation with ethylene oxide gas. The purpose of defatting and freeze-drying was to facilitate subsequent sterilisation by eliminating the barrier to diffusion of the gas into bone, to lower residual levels of ethylene oxide and its toxic by-products, to eliminate alloantigens and to make storage possible at room temperature. The efficacy and safety of the method were evaluated by testing the sterilisation of infected bone from 6 patients with active chronic osteomyelitis, the penetration of ethylene oxide into human femoral heads treated by this or by freeze-drying or freeze-thawing, and the desorption of ethylene oxide and its toxic by-products from pieces of bone treated by these methods. All the samples of infected bone tested negative for bacteria after treatment. The gas penetrated into the central area of the femoral heads in a few hours. Residual levels of ethylene oxide and its toxic by-products were much lower in the treated bone than in freeze-dried or freeze-thawed bone, and decreased quickly in flowing air. Prior defatting and freeze-drying facilitated penetration of ethylene oxide into bone during sterilisation and the desorption of ethylene oxide and its toxic by-products after sterilisation. Preparation under clean, but not sterile, conditions and storage at room temperature make bone banking more practical and efficient.


Assuntos
Transplante Ósseo , Preservação Biológica/métodos , Esterilização/métodos , Osso e Ossos/química , Osso e Ossos/efeitos dos fármacos , Clorofórmio/farmacologia , Óxido de Etileno/análise , Liofilização/métodos , Humanos , Lipídeos , Metanol/farmacologia , Bancos de Tecidos
17.
Int Orthop ; 20(3): 147-52, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8832316

RESUMO

We used bone allograft treated by defatting in chloroform and methanol, freeze-drying and sterilisation with ethylene oxide gas in operations on 396 patients. The purpose of defatting and freeze-drying is to facilitate subsequent sterilisation by eliminating a barrier to the diffusion of ethylene oxide gas into bone, to lower the residual levels of the ethylene oxide and its toxic by-products after sterilisation, to eliminate alloantigens and to make storage at room temperature possible. Postoperative infections confirmed by a positive bacterial culture occurred in 2 of the 396 patients receiving the allograft, which was prepared under clean, but not sterile, conditions, one of which was thought to be due to dehiscence of the wound, rather than to the allograft. There were also 3 probable infections. Histological sections of the area around the interface of the allograft and its bony bed showed: (1) osteoblasts lining the surface of the dead cortical bone of the graft with appositional new bone; (2) ingrowth of new bone into the Haversian canals, and (3) little infiltration of inflammatory small round cells. These findings indicated the ability of the bone to support new bone formation and to eliminate antigens. The low incidence of infection confirmed the efficacy of this method of sterilisation.


Assuntos
Doenças Ósseas/cirurgia , Transplante Ósseo , Esterilização/normas , Adolescente , Adulto , Osso e Ossos/efeitos dos fármacos , Criança , Clorofórmio/farmacologia , Óxido de Etileno/toxicidade , Estudos de Avaliação como Assunto , Feminino , Liofilização , Humanos , Lipídeos , Masculino , Metanol/farmacologia , Esterilização/métodos , Bancos de Tecidos , Transplante Homólogo
18.
Biol Pharm Bull ; 18(12): 1714-7, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8787794

RESUMO

Laminin-related peptide poly(ethylene glycol) hybrid, Tyr-Ile-Gly-Ser-Arg-aminopoly(ethylene glycol) was prepared by the solution method and carboxylated poly(ethylene glycol)-Tyr-Ile-Gly-Ser-Arg was prepared by the solid phase method. Their inhibitory effects on experimental tumor metastasis were examined in mice. The inhibitory effect of Tyr-Ile-Gly-Ser-Arg was significantly potentiated by hybrid formation with poly(ethylene glycol) either at amino- or carboxyl terminals of the peptide. Of the hybrids, Tyr-Ile-Gly-Ser-Arg-amino(polyethylene glycol) #6000 hybrid exhibited about 10 times more potent anti-metastatic effect than the peptide itself. The inhibitory effect of a mixture of the carboxylated poly(ethylene glycol) hybrid and Arg-Gly-Asp-aminopoly(ethylene glycol) hybrid also exhibited an inhibitory effect.


Assuntos
Antineoplásicos/farmacologia , Laminina/análogos & derivados , Laminina/farmacologia , Metástase Neoplásica/prevenção & controle , Neoplasias Experimentais/tratamento farmacológico , Oligopeptídeos/farmacologia , Polietilenoglicóis/farmacologia , Sequência de Aminoácidos , Animais , Camundongos , Dados de Sequência Molecular , Neoplasias Experimentais/patologia
19.
J Bone Joint Surg Br ; 77(1): 60-3, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7822398

RESUMO

A combined open and percutaneous operative technique has been devised for repair of tendo Achillis. This minimises postoperative scarring. We compared the long-term results of 12 patients treated by this method with the results of 10 who had undergone an open repair. The combined open and percutaneous repair gave significantly better relief of symptoms during everyday activities (p < 0.05), better single-limb hopping (p < 0.02) and a greater chance of returning to sport (p < 0.01). There were no significant differences between the two treatments as regards to active range of ankle motion, calf circumference or the ability to stand on tiptoe. The new technique gave better cosmetic results.


Assuntos
Tendão do Calcâneo/lesões , Tendão do Calcâneo/cirurgia , Traumatismos em Atletas/cirurgia , Adulto , Raquianestesia , Traumatismos em Atletas/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Ruptura , Procedimentos Cirúrgicos Operatórios/métodos , Técnicas de Sutura , Resultado do Tratamento
20.
Artigo em Inglês | MEDLINE | ID: mdl-7824531

RESUMO

To evaluate the effect of prostaglandin E1 (PGE1) induced hypotension on spinal blood flow (SBF) during spinal surgery, SBF was measured under isoflurane anaesthesia by the heat clearance method in 10 patients with spinal tumour. An initial dose of 0.1 microgram/kg/min of PGE1 was administered intravenously after spinal opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. PGE1 was discontinued at the completion of the operative produces. After starting PGE1, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the hypotensive effect of PGE1 remained constant at 60 min after its discontinuation. Heart rate (HR) did not change throughout the study. SBF showed no change over the course of PGE1 induced hypotension (preinfusion: 47.8 +/- 21.7 ml/100 g/min, at 15 min: 41.2 +/- 16.9 ml/100 g/min, at 30 min: 40.4 +/- 16.8 ml/100 g/min, and at 60 min: 46.1 +/- 16.3 ml/100 g/min, respectively). These results suggest that PGE1 may be a useful drug for hypotensive anaesthesia in surgery for spinal cord tumours because PGE1 maintained SBF.


Assuntos
Alprostadil/farmacologia , Hipotensão Controlada , Medula Espinal/irrigação sanguínea , Idoso , Feminino , Humanos , Período Intraoperatório , Isquemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Decúbito Ventral , Estudos Prospectivos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Neoplasias da Medula Espinal/cirurgia
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