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1.
Chemistry ; 30(38): e202400986, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38705867

RESUMEN

As the global surfactant market continues to expand, there is an increasing need to develop bio-based alternatives in the shift towards a circular economy. This study focuses on the synthesis of polar, amphoteric, amine-oxide surfactants starting from biomass-derived monosaccharides and demonstrating their potential in various applications. The synthesis involved a reductive amination of the sugars with an alkylamine and formaldehyde followed by oxidation to produce N-oxide surfactants. These bio-based surfactants exhibited promising properties, including high solubility, foamability, surface tension reduction, and critical micelle concentration. In particular, N-GalA1.10 and N-GalA1.12 showed comparable performance to commercial surfactants. Furthermore, these bio-based surfactants demonstrated significantly lower skin irritation potential when compared to petrochemical-derived counterparts like sodium laureth sulfate (SLES), making them potentially suitable for personal care products. The biodegradability assessment revealed that N-GalA1.12 exhibited good biodegradation, indicating its potential environmental compatibility. In conclusion, this study highlights the potential of bio-based N-oxide surfactants derived from monosaccharides as sustainable and skin-friendly alternatives to traditional amphoteric surfactants, like cocamidopropyl betaine (CAPB).

2.
ACS Sustain Chem Eng ; 11(45): 16117-16123, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-38022738

RESUMEN

Herein, we report a method for the synthesis of biobased surfactants derived from sugar beet pulp (SBP) monosaccharides, l-Ara and d-GalA. The surfactants were prepared via one-pot reductive amination, allowing the introduction of different alkyl chain lengths and methyl modifications. Optimal reaction conditions were established to achieve high yields and easy purification. The synthesized surfactants including the tertiary amines exhibited desirable properties, including solubility, foamability, and reduction of surface tension. Notably, the anionic surfactants derived from d-GalA demonstrated better solubility and foam performance compared to those derived from l-Ara. In addition, these surfactants exhibited surface tension and critical micelle concentration (CMC) comparable to those of the commercial surfactant sodium lauryl ether sulfate (SLES). Furthermore, the biodegradable surfactant GalA1.8 displayed excellent emulsifying properties and low skin irritation potential. On the l-Ara surfactant with a short chain, Ara1.6 has potential as a hydrotrope. These findings suggest that biobased surfactants derived from SBP monosaccharides have promising applications in various industries, including pharmaceuticals, cosmetics, detergents, and chemicals.

4.
BJOG ; 129(11): 1908-1915, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35289051

RESUMEN

OBJECTIVE: To analyse the efficacy of sacrospinous ligament (SSL) suture removal on the reduction of pain symptoms in the case of suspected pudendal nerve entrapment after sacrospinous ligament fixation (SSLF). DESIGN: Retrospective cohort study. SETTING: Tertiary referral centre, the Netherlands. POPULATION: A cohort of 21 women having their SSLF sutures removed because of SSLF-related pain symptoms. METHODS: Clinical record review. MAIN OUTCOME MEASURES: The primary outcome was reduction of pain after SSL suture removal. Secondary outcome measures were time interval between suture placement and suture removal, complete suture removal, adverse events and recurrence of pelvic organ prolapse (POP). RESULTS: A total of 21 women underwent SSL suture removal for severe and/or persistent pain, which was confirmed on clinical examination: 95% of the women (20/21) reported pain reduction after suture removal, and 57% reported complete pain relief. The time interval between suture placement and suture removal was at a median of 414 days (range 8-1855 days). Sutures could be completely removed in 86% of cases (18/21). One woman had excessive blood loss (520 ml) without blood transfusion. At 6-8 weeks after surgery, 10% of the women (2/21) had renewed symptomatic POP, stage ≥ 2, for which additional POP surgery was indicated. CONCLUSIONS: When performed by an experienced clinician, SSL suture removal is feasible and efficacious, with low morbidity. In addition, the risk of recurrent POP in the short term appeared to be low. TWEETABLE ABSTRACT: The surgical removal of sacrospinous ligament sutures is safe and efficacious for pain relief, even remote from initial placement.


Asunto(s)
Prolapso de Órgano Pélvico , Neuralgia del Pudendo , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Humanos , Ligamentos/cirugía , Prolapso de Órgano Pélvico/etiología , Prolapso de Órgano Pélvico/cirugía , Neuralgia del Pudendo/etiología , Neuralgia del Pudendo/cirugía , Estudios Retrospectivos , Suturas/efectos adversos , Resultado del Tratamiento
7.
Int Urogynecol J ; 29(6): 789-793, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29564509

RESUMEN

Midurethral slings are the mainstay of treatment for stress urinary incontinence. The role of cystourethroscopy to detect lower urinary tract injury following retropubic midurethral slings is well-established; however, its role following transobturator or single-incision sling placement remains controversial. Some advocate "routine" whereas others advocate for "selective" cystourethroscopy. This paper reviews the arguments for and against cystourethroscopy to detect lower urinary tract injury following transobturator and single-incision slings.


Asunto(s)
Cistoscopía , Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Humanos , Resultado del Tratamiento , Vejiga Urinaria , Procedimientos Quirúrgicos Urológicos/métodos
9.
Int Urogynecol J ; 26(1): 33-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24859796

RESUMEN

INTRODUCTION AND HYPOTHESIS: Our aim was to estimate agreement between transperineal and endovaginal ultrasound in assessing levator ani biometry and avulsion in nullipara and primipara women and determine agreement between levator avulsion palpation and ultrasound. METHODS: This longitudinal cohort study assessed 269 nullipara women at 36 weeks gestation and 191 primipara women 13 weeks postpartum. Women underwent levator palpation, and avulsion was diagnosed if no attachment to the pubic bone was felt. Subsequently, 3/4D transperineal and 3D endovaginal ultrasound were performed. A standardized protocol was used to perform measurements at rest. Levator avulsion was diagnosed on endovaginal ultrasound at rest if >50 % was avulsed and on transperineal tomographic ultrasound imaging at maximum contraction if the central three slices were avulsed. Levator avulsion was analyzed by two independent, blinded investigators. A third investigator resolved discrepancies. Intraclass correlation coefficient and limits of agreement were calculated for each time point. RESULTS: Intraclass correlation coefficient for levator urethra gap was 0.44-0.54, hiatus area 0.76-0.79, transverse diameter 0.51-0.59, anteroposterior diameter 0.70-0.72. Levator thickness correlated poorly. Endovaginal ultrasound measurements were generally smaller; however limits of agreement were acceptable for hiatus measurements. Overall agreement between both ultrasound techniques in diagnosing levator avulsion was 95 %; correlation 0.72 [95 % confidence interval (CI) 0.67-0.76]. Agreement between palpation and transperineal ultrasound was 92 % (kappa = 0.34), and between palpation and endovaginal ultrasound was 92 % (kappa = 0.37). CONCLUSIONS: Transperineal and endovaginal ultrasound can both be used to analyze hiatus area and anteroposterior diameter with the patient at rest and to diagnose levator avulsion. Palpation correlates only fairly with both methods.


Asunto(s)
Trastornos del Suelo Pélvico/diagnóstico por imagen , Diafragma Pélvico/lesiones , Adulto , Femenino , Humanos , Estudios Longitudinales , Palpación , Embarazo , Estudios Prospectivos , Ultrasonografía/métodos , Adulto Joven
10.
Int Urol Nephrol ; 46(4): 711-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24136184

RESUMEN

PURPOSE: To investigate the role of the Prostate Health Index (phi) in prostate cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population. METHODS: This was a retrospective study of archived serum samples from patients enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10 ng/mL, a negative digital rectal examination, and received their first prostatic biopsy between April 2008 and April 2013, were recruited. The serum sample collected before biopsy was retrieved for the measurement of various PSA derivatives and the phi value was calculated for each patient. The performance of these parameters in predicting the prostatic biopsy results was assessed. RESULTS: Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed with PCa, were recruited for this study. Statistically significant differences between PCa patients and non-PCa patients were found for total PSA, PSA density, [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio (%p2PSA), and phi. The areas under the curve of the receiver operating characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were 0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients. CONCLUSIONS: Use of the phi could improve the accuracy of PCa detection in patients with an elevated PSA level and thus avoid unnecessary prostatic biopsies.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno Prostático Específico/sangre , Próstata/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Pueblo Asiatico , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tamaño de los Órganos , Valor Predictivo de las Pruebas , Isoformas de Proteínas/sangre , Curva ROC , Estudios Retrospectivos
11.
Br J Anaesth ; 113(1): 138-47, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24129596

RESUMEN

BACKGROUND: Spinal serotonin (5-HT) receptors 3 (5-HT3R) and 7 (5-HT7R) are differentially involved in facilitatory or inhibitory descending modulation, respectively. Electrophysiological studies of the spinal cord have demonstrated that 5-HT3R is involved in nociception induced by intraplantar injection of formalin, but not carrageenan. In addition, depletion of spinal serotonin has been shown to attenuate pain behaviour in the formalin test, but there have been no such reports regarding the carrageenan model. This study compared the role of 5-HT7R and the influence of descending serotonergic modulation between formalin- and carrageenan-induced inflammatory pain. METHODS: Effects of intrathecal (i.t.) AS-19 (5-HT7R agonist) and SB-269970 (5-HT3R antagonist) on flinching response in the formalin test and mechanical allodynia in the carrageenan model were evaluated in male Sprague-Dawley rats. The effect of serotonin depletion by i.t. 5,7-dihydroxytryptamine was also examined in the two models. RESULTS: Intrathecal AS-19 significantly reduced the flinching responses in the formalin test (P<0.01), which was reversed by i.t. SB269970. However, neither AS-19 nor SB269970 produced a significant change in mechanical allodynia in the carrageenan model. Depletion of spinal serotonin attenuated the flinching response in phase 2 of the formalin test (P<0.01), but increased mechanical allodynia in the carrageenan model compared with controls (P<0.01). CONCLUSIONS: Spinal 5-HT7R plays a significant inhibitory role in descending serotonergic modulation in pain induced by formalin but not carrageenan. Descending serotonergic modulation is differentially involved in inflammatory pain induced by formalin and carrageenan, with facilitatory and inhibitory effects, respectively.


Asunto(s)
Dolor/fisiopatología , Receptores de Serotonina/fisiología , Serotonina/fisiología , Animales , Carragenina , Modelos Animales de Enfermedad , Formaldehído , Hiperalgesia/inducido químicamente , Hiperalgesia/fisiopatología , Inflamación/inducido químicamente , Inflamación/fisiopatología , Masculino , Dolor/inducido químicamente , Dimensión del Dolor/métodos , Umbral del Dolor/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de Serotonina 5-HT3/fisiología , Serotonina/deficiencia , Serotonina/metabolismo , Médula Espinal/metabolismo
12.
J Nanosci Nanotechnol ; 12(4): 3669-72, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22849193

RESUMEN

The effect of precursor ratio (H2O/DEZ) on the texture orientation, surface morphology, optical transparency and electrical resistivity of ZnO thin films deposited by MOCVD was investigated. Deposition temperature and pressure were fixed at 120 degrees C and 0.67 torr, respectively. The precursor ratio was varied between 0.1 and 4. It was found that the texture orientation changed from (0002) to (1120) with increase of the precursor ratio. (1120) textured film shows well facetted tetrapod like rough surface morphology, which scatters the incident light very effectively. The electrical resistivity was in the range of about 0.1 omega cm in the undoped state, which was found to decrease with increase of the film thickness and decrease of the precursor ratio.

13.
J Urol ; 188(3): 837-42, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22819406

RESUMEN

PURPOSE: We assessed the effects of different shock wave delivery rates in patients treated with shock wave lithotripsy for renal stones, particularly treatment success, degree of renal injury and pain experienced, and analgesic demand. MATERIALS AND METHODS: A total of 206 patients with renal stones were prospectively randomized to receive shock waves delivered at 60 (group 1) or 120 (group 2) shocks per minute using a Sonolith® Vision at a single institution in October 2008 and August 2010. The primary outcome was successful treatment 12 weeks after 1 lithotripsy session. Secondary outcome measures included the degree of renal injury, as reflected by changes in urinary markers of renal injury, as well as patient pain scores and analgesia consumed during treatment. RESULTS: Mean stone size in groups 1 and 2 was 8.95 and 9.28 mm, respectively (p = 0.525). The overall treatment success rate was 43.2%. It was significantly better in group 1 than in group 2 (50.5% vs 35.9%, p = 0.035). There was no between group difference in the success rate for stones 10 mm or less but the success rate was statistically better for group 1 patients with stones greater than 10 mm (p = 0.002). Immediately after shock wave lithotripsy there was a statistically significant greater increase in urinary NAG (p = 0.003) and interleukin-18 (p = 0.022) in group 1. There was no between group difference in pain scores, analgesic consumption during shock wave lithotripsy or unplanned hospital visits. CONCLUSIONS: Slower shock wave delivery yielded better treatment outcomes, particularly for stones greater than 10 mm, without increasing patient pain or analgesic demand. However, slower shock wave delivery also appeared to cause a statistically significant increase in acute renal injury markers, although the clinical implication was uncertain.


Asunto(s)
Cálculos Renales/terapia , Litotricia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Riñón/lesiones , Litotricia/efectos adversos , Masculino , Persona de Mediana Edad , Dolor/etiología , Estudios Prospectivos , Método Simple Ciego
15.
Br J Anaesth ; 107(6): 930-3, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21903640

RESUMEN

BACKGROUND: Paradoxical excitement response during sedation consists of loss of affective control and abnormal movements. Chronic alcohol abuse has been proposed as a predisposing factor despite lack of supporting evidence. Because alcohol and propofol have a common site of action, we postulated that paradoxical excitement responses during propofol-induced sedation occur more frequently in hazardous and harmful alcohol drinkers than in social or non-drinkers. METHODS: One hundred and ninety patients undergoing orthopaedic knee joint surgery were enrolled in this prospective and observational study. Subjects were divided into Group HD (hazardous and harmful drinkers) or Group NHD (no hazardous drinkers) according to the alcohol use disorder identification test (AUDIT). In study 1, propofol infusion was adjusted to achieve the bispectral index at 70-80 using target-controlled infusion. In study 2, the target concentration of propofol was fixed at 0.8 (study 2/Low) or 1.4 µg ml(-1) (study 2/High). Paradoxical excitement responses were categorized by intensity into mild, moderate, or severe. RESULTS: The overall incidence of paradoxical excitement response was higher in Group HD than in Group NHD in study 1 (71.4% vs 43.8%; P=0.022) and study 2/High (70.0% vs 34.5%; P=0.006) but not in study 2/Low. The incidence of moderate-to-severe response was significantly higher in Group HD of study 1 (28.6% vs 3.1%; P=0.0005) and study 2/High (23.3% vs 3.4%; P=0.029) with no difference in study 2/Low. Severe excitement response occurred only in Group HD of study 1 and study 2/High. CONCLUSIONS: Paradoxical excitement occurred more frequently and severely in hazardous and harmful alcohol drinkers than in social drinkers during propofol-induced moderate-to-deep sedation, but not during light sedation.


Asunto(s)
Consumo de Bebidas Alcohólicas/fisiopatología , Hipnóticos y Sedantes/farmacología , Propofol/farmacología , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
16.
Br J Anaesth ; 106(3): 371-9, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21169610

RESUMEN

BACKGROUND: We defined the nature of the pharmacological interaction after intrathecal co-administration of ginsenosides with clonidine, and clarified the contribution of the α-2 adrenoceptors on the effect of ginsenosides. METHODS: Pain was evoked by injection of a formalin solution (5%, 50 µl) into the hindpaw of male Sprague-Dawley rats. Isobolographic analysis was performed to characterize the drug interaction between ginsenosides and clonidine. The antagonism of ginsenosides-mediated antinociception was determined with α-2A (BRL 44408), α-2B (ARC 239), and α-2C (JP 1302) adrenoceptor antagonists. The expression of α-2 adrenoceptor subtypes was examined by reverse transcriptase-polymerase chain reaction. RESULTS: Intrathecal ginsenosides (n=29) and clonidine (n=31) displayed an antinociceptive effect. The ED(50) values (95% confidence intervals) of ginsenosides and clonidine for phases 1 and 2 were 109.5 (63-190.3) and 110.9 (57.1-215.5), and 11.8 (3.7-37.1) and 4.9 (3.1-6.7) µg, respectively. With an isobolographic study (n=48), the ED(50) values (95% confidence intervals) of ginsenosides in the combination of ginsenosides and clonidine for phases 1 and 2 were 58.2 (38.9-87.3) and 57.2 (46.5-70.3) µg, respectively. Intrathecal BRL 44408 (n=6), ARC 239 (n=5), and JP 1302 (n=5) reversed the antinociception of ginsenosides in both phases (P<0.01, <0.001). The injection of formalin increased the expression of α-2C adrenoceptor in the spinal cord (P<0.05). CONCLUSIONS: Intrathecal ginsenosides additively interacted with clonidine in the formalin test. Furthermore, α-2A, -B, and -C adrenoceptors contributed to the antinociception of intrathecal ginsenosides.


Asunto(s)
Analgésicos no Narcóticos/farmacología , Clonidina/farmacología , Ginsenósidos/farmacología , Dolor/prevención & control , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Animales , Conducta Animal/efectos de los fármacos , Clonidina/administración & dosificación , Clonidina/uso terapéutico , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Interacciones Farmacológicas , Regulación de la Expresión Génica/efectos de los fármacos , Ginsenósidos/administración & dosificación , Ginsenósidos/uso terapéutico , Inyecciones Espinales , Masculino , Dolor/inducido químicamente , Dimensión del Dolor/métodos , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 2/biosíntesis , Receptores Adrenérgicos alfa 2/genética
17.
Minerva Anestesiol ; 76(7): 554-8, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20613698

RESUMEN

Intracerebral hemorrhage is an unusual complication of autonomic hyperreflexia (AHR), which can be fatal if massive bleeding occurs with subsequent brain herniation. Episodes of AHR are most often triggered by bladder and rectal distention. We present a case of a 45-year-old quadriplegic male who suffered left basal ganglia and thalamic hemorrhage associated with AHR during surgery for pressure sore defects in the prone position under local anesthesia. Early recognition and removal of triggering factors of AHR failed to bring his blood pressure under control. The patient continued to deteriorate neurologically and died 9 days after the attack. A preventive measure rather than episodic treatment of AHR may be of paramount importance to avoid life-threatening complications, especially when a patient with a history of AHR is undergoing surgery in the prone position.


Asunto(s)
Disreflexia Autónoma/complicaciones , Hemorragia Cerebral/etiología , Complicaciones Intraoperatorias/etiología , Posicionamiento del Paciente , Cuadriplejía/complicaciones , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Posición Prona
18.
J Hosp Infect ; 48(4): 281-8, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11461129

RESUMEN

Klebsiella oxytoca strains resistant to both aztreonam and ceftriaxone were isolated from six neonates in a neonatal intensive care unit and water reservoirs of two humidifiers attached to the neonatal incubators. These isolates were assumed to be of the same clone because they were characterized by the same antimicrobial susceptibility and pulsed field gel electrophoresis patterns. It was established that the drug resistance was attributed to overproduction of chromosomally encoded Kl beta-lactamase. It was determined that an isolate (K. oxytoca H1) contained a high enzyme concentration (27microg/100microg of protein in enzyme extracts), at least 27 times higher than the control K. oxytoca N1. It was also demonstrated that isolates had a point mutation in the - 35 concensus region of the promotor gene of bla(OXY-2)leading to enzyme overproduction. Outbreaks caused by K1 hyperproducers have not previously been described.


Asunto(s)
Aztreonam/farmacología , Proteínas Bacterianas , Infección Hospitalaria/epidemiología , Infecciones por Klebsiella/epidemiología , Klebsiella/efectos de los fármacos , Klebsiella/genética , Resistencia betalactámica , Ceftriaxona/farmacología , Electroforesis en Gel de Campo Pulsado , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Klebsiella/enzimología , Pruebas de Sensibilidad Microbiana , Mutación Puntual , Reacción en Cadena de la Polimerasa , Resistencia betalactámica/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo
19.
Mol Cells ; 10(5): 498-504, 2000 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-11101139

RESUMEN

Human neutrophil elastase (HNE, IEC 3. 4. 21. 37) is a causative factor of inflammatory diseases, including emphysema and rheumatoid arthritis. Enzymatic characterization is important for the development of new drugs involved in the regulation of this enzyme. In this study, we investigated the enzymatic and biochemical properties of five different elastolytic enzymes, with a molecular mass between 24 kDa and 72 kDa. Three elastases, molecular masses of 27, 29, 31 kDa, might be elastase isozymes that have the same NH2-terminal amino acid sequences of Ile-Val-Gly-Gly-Arg-Arg-Ala. The 24-kDa enzyme, which showed the identical NH2-terminal amino acid sequences to elastase, was a degraded fragment of native elastase. The elastolytic activity was conserved at the 6/7 domain of the NH2-terminal region. The inhibitory characteristics of PMSF, DipF were the same as those of native elastases. The 72-kDa molecule, which showed elastolytic activity, might be a trimer formed between native elastases (31 kDa and 29 kDa) and a cathepsin G-like enzyme, which did not show elastolytic activity but enhanced the elastolytic activity of neutrophil elastase. Although this cathepsin G-like enzyme showed weak cathepsin G activity, it has distinguishable NH2-terminal sequences of Ile-Val-Gly-Gly-Ser-Arg-Ala- from those of elastase or cathepsin G. The potentiation of elastolytic activity could be a result of the trimerization of native elastase with a cathepsin G-like enzyme, and was then weakly inhibited by serine protease inhibitors, such as PMSF, DipF. Therefore, we suggest the cathepsin G-like enzyme to be a novel enzyme, which has an important role in the development of inflammation.


Asunto(s)
Catepsinas/sangre , Elastasa de Leucocito/sangre , Neutrófilos/enzimología , Secuencia de Aminoácidos , Catepsina G , Catepsinas/química , Catepsinas/aislamiento & purificación , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Cristalografía por Rayos X , Humanos , Isoenzimas/sangre , Isoenzimas/química , Isoenzimas/aislamiento & purificación , Cinética , Elastasa de Leucocito/química , Elastasa de Leucocito/aislamiento & purificación , Modelos Moleculares , Peso Molecular , Fragmentos de Péptidos/química , Estructura Terciaria de Proteína , Serina Endopeptidasas
20.
Exp Mol Med ; 32(3): 146-54, 2000 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-11048646

RESUMEN

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Elastasa de Leucocito/antagonistas & inhibidores , Cromatografía de Afinidad , Simulación por Computador , Inhibidores Enzimáticos/farmacología , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/aislamiento & purificación , Cetoprofeno/farmacología , Elastasa de Leucocito/aislamiento & purificación , Modelos Moleculares , Naproxeno/farmacología , Fenilbutazona/análogos & derivados , Salicilatos/farmacología , Espectrometría Raman
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