RESUMEN
BACKGROUND: Diabetic retinopathy (DR) is the leading cause of vision loss among adults in the USA. Vision loss associated with diabetic retinopathy can be prevented with timely ophthalmologic care, and therefore, it is recommended that individuals with diabetes have annual retinal examinations. There is limited evidence on whether using telemedicine to screen for DR in primary care clinics in the USA effectively leads to increased DR screening rates. The objective of this systematic review is to collate evidence from existing studies to investigate the effectiveness of telemedicine DR screening (TDRS) in primary care clinics on DR screening rates. METHODS: Relevant studies will be identified through searching MEDLINE/PubMed interface, Scopus, and Web of Science from their inception until November 2021, as well as searching reference lists of included studies and previous related review articles or systematic reviews. There will be no restrictions on study design. Eligible studies will include subjects with either type 1 or type 2 diabetes, will evaluate telemedicine technology for screening of DR, will have been conducted in the USA, and will report DR screening rates or data necessary for calculating such rates. Two reviewers will screen search results independently. Risk-of-bias assessment and data extraction will be carried out by two reviewers. The version 2 of the Cochrane risk-of-bias tool (RoB 2) and the Newcastle-Ottawa scale (NOS) tool will be used to assess the quality and validity of individual studies. If feasible, we will conduct random-effects meta-analysis where appropriate. If possible, we will conduct subgroup analyses to explore potential heterogeneity sources (setting, socio-economic status, age, ethnicity, study design, outcomes). We will disseminate the findings through publications and relevant networks. DISCUSSION: This protocol outlines the methods for systematic review and synthesis of evidence of TDRS and its effect on DR screening rates. The results will be of interest to policy makers and program managers tasked with designing and implementing evidence-based services to prevent and manage diabetes and its complications in similar settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021231067.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Telemedicina , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/diagnóstico , Tamizaje Masivo , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Telemedicina/métodosRESUMEN
BACKGROUND: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America. METHODS: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact. RESULTS: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care. CONCLUSIONS: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes. LAY SUMMARY: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes.
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Oncología Médica , Neoplasias , Niño , Humanos , América Latina , Hospitales Pediátricos , HospitalizaciónRESUMEN
PURPOSE: To compare effects of the MKO Melt (midazolam 3 mg, ketamine 25 mg, and ondansetron 2 mg) with intravenous (IV) sedation on vital signs of patients who underwent cataract surgery. SETTING: Two private ophthalmology practices in Sioux Falls, South Dakota, USA. DESIGN: Retrospective analysis. METHODS: Preoperative, intraoperative, and postoperative vital signs were compared between individuals who underwent cataract surgery and received exclusively either MKO (n = 991) or traditional IV methods (n = 120) for sedation. Clinical significance was defined as a 5 mm Hg change in blood pressure, 3 beats per minute (bpm) change in heart rate, a change of 2 respirations per minute, or a change of 3% in O2 saturation. MKO Melt but not IV sedation was given before the reported preoperative vital signs. RESULTS: There were 1111 patients included in this study. Preoperative systolic blood pressure (SBP) was 133.7 ± 15.6 mm Hg in the MKO group and 139.6 ± 17.3 mm Hg in the IV group (P = .0001). Postoperative SBP was 130.8 ± 12.9 mm Hg in the MKO group and 135.8 ± 19.3 mm Hg in the IV group (P < .01). Postoperative heart rate was 66.3 ± 10.4 bpm in the MKO group compared with 69.8 ± 10.5 bpm in the IV group (P < .001). No other clinically and statistically significant differences were found. The mean number of melts used was 1.5. CONCLUSIONS: Clinically and statistically significant improvements in preoperative and postoperative SBP and postoperative heart rate were observed in patients who received MKO Melt. The MKO Melt was safe, effective, and well tolerated and a viable alternative to IV sedation.
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Ketamina , Midazolam , Presión Sanguínea , Sedación Consciente , Humanos , Hipnóticos y Sedantes/farmacología , Ketamina/farmacología , Midazolam/farmacología , Ondansetrón/farmacología , Estudios RetrospectivosRESUMEN
BACKGROUND: Use of procedural sedation to promote anxiolysis, analgesia, and amnesia enhances both pediatric patient experience and procedural outcomes. Sanford Children's outpatient sedation clinic currently uses oral midazolam for minimal sedation. METHODS: A research survey was designed to evaluate parent/guardian satisfaction with midazolam for pediatric sedation in simple outpatient procedures including, bot linum toxin injections, voiding cystourethrogram (VCUG), and intravenous line placement. Parents'/ guardians' understanding of the sedation and procedural logistics were surveyed and their satisfaction with the child's comfort, recovery time, and overall satisfaction were assessed. Each component was rated on a scale of 1-10, 1 being not satisfied and 10 as extremely satisfied. RESULTS: The study was conducted at a single pediatric outpatient center. Forty-one parents/guardians of patients aged 22 months-17 years were recruited; of these, 41 consented and enrolled in the study. Average age was 6.1 years with 22 females and 19 males. Of the surveys collected, 30 were botulinum toxin injections, eight VCUG, one contrast enema, and two were not recorded. Mean survey results were 8.7 (95 percent CI, 8.2-9.2) for satisfaction of recovery time, 8.0 (95 percent CI, 7.4-8.6) for control of discomfort and 8.4 (95 percent CI, 7.9-8.9) for overall satisfaction. CONCLUSION: When evaluating midazolam as a sedation agent in pediatric procedures, parents/guardians were most satisfied with the duration of recovery and had the lowest satisfaction on control of the patient's discomfort. Overall, it can be concluded that midazolam is a moderately good agent for pediatric patients receiving minimal sedation, with the greatest satisfaction in the duration of recovery.
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Sedación Consciente , Midazolam , Niño , Femenino , Humanos , Lactante , Masculino , Midazolam/uso terapéutico , Padres , Satisfacción Personal , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The objective of this study was to study the effect of electronic video education on patient's self-assessed perception of knowledge about pelvic floor disorders in relation to obesity in a prospective randomized controlled trial. METHODS: From June to July 2015, women with a body mass index of 25 kg/m or higher seeking care at a single urogynecology center were recruited and randomized into either a standard visit with an 8-minute video (group A) or a standard visit control (group B). Randomization was performed with computer-generated number blocks of 4. Allocation sequence was concealed from the caregiver, in sequentially numbered, opaque, and sealed envelopes. Immediately after their visit, patients answered a series of 3 questionnaires, which were statistically analyzed using unpaired t tests, Wilcoxon rank sum and analysis of variance tests, presented as mean and standard deviation. Primary outcome was a difference in self-assessed perception of knowledge questionnaire scores. Secondary outcome was a difference in motivation to lose weight. RESULTS: Forty-eight women enrolled, and 40 completed all questionnaires, 20 in each group. Representation in both groups was demographically similar. The mean (SD) answers for the postvisit survey measuring participant's self-assessed perception of knowledge was 3.9 (0.8) for group A and 3.5 (1.1) for group B (P = 0.002). Ninety percent of women in group A reported motivation to lose weight, compared with 75% in group B (P = 0.4). CONCLUSIONS: Participants who received electronic video education scored significantly higher on self-assessed perception of knowledge questionnaire about pelvic floor disorders in relation to obesity. The video did not increase motivation to lose weight.
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Información de Salud al Consumidor/métodos , Obesidad/complicaciones , Trastornos del Suelo Pélvico/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Persona de Mediana Edad , Proyectos Piloto , Encuestas y Cuestionarios , Grabación en VideoRESUMEN
Introducción: los lípidos presentes en las semillas de Cucurbita pepo L. ricos en ácidos grasos poliinsaturados han demostrado tener acción antiinflamatoria en la hiperplasia prostática benigna. El empleo de la energía de las microondas en la extracción de compuestos de origen natural tiene como ventaja principal, la rapidez del calentamiento, que permite significativos ahorros de tiempo y en consecuencia energía en el proceso, todo lo cual se manifiesta en una reducción de los costos en general. Objetivos: estudiar el efecto del tiempo en la obtención de los lípidos contenidos en las semillas de Cucurbita pepo L. mediante la extracción asistida por microondas. Métodos: se estudiaron diferentes tiempos (1, 5, 10 y 15 min) para extraer los lípidos de las semillas de Cucurbita pepo L., empleando etanol como disolvente. Se evaluó mediante espectroscopia de reflexión interna y cromatografía gaseosa la presencia de los ácidos grasos mayoritarios responsables de la actividad farmacológica. Resultados: se demostró que el tiempo de extracción de 1 min era el más adecuado. El análisis cualitativo y cuantitativo mediante espectroscopia de reflexión interna y cromatografía gaseosa, respectivamente, evidenció la presencia de los ácidos grasos en proporción mayoritaria reportados en la literatura con actividad sobre la hiperplasia prostática benigna. Conclusiones: los resultados demostraron la factibilidad del empleo de la energía de las microondas en la extracción del componente lipídico a partir de las semillas de Cucurbita pepo L
Introduction: lipids from Cucurbita pepo L. seeds, rich in polyunsaturated fatty acids, show an effective antiinflammatory effect in the treatment of benign prostatic hyperplasia (BPH). The use of microwave energy in the extraction of natural compounds has among its main advantages quick heating, which saves time and energy in the process, thus reducing the general costs. Objectives: to study different extraction times to obtain lipids from Cucurbita pepo L. seeds through microwave-assisted extraction. Methods: lipids from Cucurbita pepo L. seeds were extracted with ethanol as solvent at several times (1, 5, 10 y 15 min).The evaluation was based on attenuated total internal reflection spectrometry and gas chromatography to detect the major fatty acids responsible for the pharmacological action. Results: the one-minute extraction time was the most efficient. Qualitative and quantitative analysis by attenuated total internal reflection spectrometry and gas chromatography indicated the presence of the major fatty acids reported in the literature as having pharmacological effect over benign prostate hyperplasia. Conclusions: the results demonstrated the feasibility of employing microwave energy in the extraction of the lipid component from Cucurbita pepo L. seeds
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Cucurbita pepo/análisis , Ácidos Grasos , Lípidos , MicroondasRESUMEN
Introducción: el clorhidrato de betaxolol es un bloqueador cardioselectivo ß1 adrenérgico, que no presenta una actividad significativa como estabilizante de membrana (anestésico local) y carece de actividad simpaticomimética intrínseca. A nivel ocular actúa disminuyendo la producción de humor acuoso, reduciendo la presión intraocular a niveles normales, ya sea acompañada o no de glaucoma. Está indicado en el tratamiento del glaucoma crónico de ángulo abierto en pacientes con presión intraocular elevada (hipertensión ocular). Objetivo: diseñar una formulación de betaxolol 0,5 por ciento colirio, que cumpla con los índices de control de calidad para esta forma farmacéutica y que proporcione el efecto terapéutico deseado. Métodos: se realizaron cuatro variantes tecnológicas, modificando convenientemente las cantidades de excipientes y manteniendo la del principio activo, para lo que se tuvo en cuenta la composición de la formulación líder, con la finalidad de seleccionar la de mejor estabilidad en 3 meses de seguimiento. Se ajustó el pH y la isotonicidad de la formulación, según las exigencias de un preparado oftálmico. La isotonicidad se alcanzó con cloruro de sodio. Resultados: el desarrollo tecnológico de la formulación resultó satisfactorio, y se obtuvo un producto que cumplió con todas las especificaciones descritas en la USP 30, para el control de la calidad del producto. La preparación mantuvo sus propiedades físicas, químicas y microbiológicas inalterables por un período de 24 meses, almacenada a una temperatura de 30,0 ± 2,0 °C. Conclusiones: la formulación de un medicamento obtenida en forma de colirio que contiene betaxolol clorhidrato como principio activo para el tratamiento del glaucoma, cumple con todas las especificaciones de calidad para este tipo de forma farmacéutica, lo cual puede aumentar el arsenal terapéutico de Cuba
Introduction: Betaxolol chlorhydrate is a cardioselective adrenergic ß1 blocker that does not play a significant role as membrane stabilizer (local anesthestic) and lacks intrinsic sympathomimetic activity. It diminishes the production of aqueous humor in the eye, thus reducing the intraocular pressure to normal, either with or without glaucoma. This drug is indicated in the treatment of chronic open angle glaucoma affecting patients with ocular hypertension. Objective: to design a formulation of 0.5 por ciento Betaxolol eye drops that meets the quality control parameters for this pharmaceutical form and that provides the desired therapeutic effect. Methods: four technological variants were performed by adequately modifying the excipient quantities and by keeping the active principle amount, for which the composition of the leading formulation was taken into account. The aim was to select the most stable variant after 3-month follow-up. The pH and the isotonicity of the formulation were adjusted for the requirements of an ophthalmologic preparation. The isotonicity was reached with sodium chloride. Results: the technological development of this formulation was satisfactory; the final product met all the specifications for the quality control of the product as described in USP 30. The physical, chemical and microbiological properties of the preparation remained unchanged for 24 months under storage conditions of 30.0 ± 2.0 °C. Conclusions: the formulation of a medical eye drops containing Betaxolol chlorhydrate as active principle, meets all the quality specifications for this pharmaceutical form to treat glaucoma, which may expand the therapeutic options in Cuba
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Estabilidad de Medicamentos , Soluciones Oftálmicas/uso terapéuticoRESUMEN
Se desarrolló una formulación para uso oftálmico, que contenía cloruro de sodio al 5 por ciento, estable desde el punto de vista físico, químico y microbiológico. Se realizaron los estudios de formulación correspondientes, seleccionándose la composición y procedimiento tecnológico más adecuados. Además, se estudió la efectividad antimicrobiana de los preservativos antimicrobianos empleados según se establece en la Farmacopea de los Estados Unidos 30 y se comprobó la seguridad del uso de este medicamento a través de los resultados del ensayo de irritabilidad oftálmica. Se elaboraron 3 lotes del medicamento y se envasaron en frascos plásticos de polietileno de baja densidad con tapa de polipropileno de alta densidad y se almacenaron a temperatura ambiente durante 24 meses; se estudió su estabilidad física y química por el método acelerado y de vida de estante. Se comprobó su estabilidad microbiológica a cada uno de los lotes elaborados, al inicio y final del estudio, según se establece en la Farmacopea de los Estados Unidos 30, y se obtuvieron resultados satisfactorios. Todos los resultados cumplieron con los límites de calidad establecidos en la literatura oficial para este tipo de forma farmacéutica, por lo que se concluyó que el medicamento desarrollado está correctamente formulado desde el punto de vista galénico con un tiempo de vida útil de 24 meses almacenado bajo las condiciones estudiadas, demostrado según el otorgamiento del certificado de registro por el organismo regulador (Centro Estatal para el Control de Medicamentos, CECMED). Finalmente el medicamento fue introducido al nivel industrial sin que se presentaran problemas tecnológicos
A formula for ophthalmic use was developed containing 5 percent sodium chloride stable from the physical, chemical and microbiological point of view. Studies of corresponding formulae were conducted selecting the more suitable composition and technological procedure. Also, the antimicrobial effectiveness of animicrobials preservatives used according to United States Pharmacopeia was studied demonstrating the safe use of this drug by the results of the ophthalmic irritability trial. Three batchs of this drug were elaborated packing in low density polyethylene plastic flasks with a high density polypropylene top stored at room temperature during 24 monhts and its physical and cchemical stability was studied y accelerated method and of shield-life. At onset and the end of study microbiological stability was demonstrate in each of batches made (30), according to USP with satisfactory results. All results fulfill with the established quality limits in official literature for this type of pharmaceutical way concluding that this developeddrug is appropriately formulated fro the doctoral point of view with a useful life time of 24 months stored under study conditions, demonstrated according to award of registry certificate by regulator institution (State Center for Drugs' Control, CECMED). Finally, the drug was introduced at industrial level without technological problems
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Química Farmacéutica , Cloruro de Sodio/uso terapéutico , Estabilidad de Medicamentos , Soluciones OftálmicasRESUMEN
The lysine biosynthetic pathway has to supply large amounts of alpha-aminoadipic acid for penicillin biosynthesis in Penicillium chrysogenum. In this study, we have characterized the P. chrysogenum L2 mutant, a lysine auxotroph that shows highly increased expression of several lysine biosynthesis genes (lys1, lys2, lys3, lys7). The L2 mutant was found to be deficient in homoaconitase activity since it was complemented by the Aspergillus nidulans lysF gene. We have cloned a gene (named lys3) that complements the L2 mutation by transformation with a P. chrysogenum genomic library, constructed in an autonomous replicating plasmid. The lys3-encoded protein showed high identity to homoaconitases. In addition, we cloned the mutant lys3 allele from the L2 strain that showed a G(1534) to A(1534) point mutation resulting in a Gly(495) to Asp(495) substitution. This mutation is located in a highly conserved region adjacent to two of the three cysteine residues that act as ligands to bind the iron-sulfur cluster required for homoaconitase activity. The L2 mutant accumulates homocitrate. Deletion of the lys1 gene (homocitrate synthase) in the L2 strain prevented homocitrate accumulation and reverted expression levels of the four lysine biosynthesis genes tested to those of the parental prototrophic strain. Homocitrate accumulation seems to act as a sensor of lysine-pathway distress, triggering overexpression of four of the lysine biosynthesis genes.
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Genes Fúngicos , Lisina/biosíntesis , Penicillium chrysogenum/genética , Penicillium chrysogenum/metabolismo , Ácidos Tricarboxílicos/metabolismo , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Clonación Molecular , Cartilla de ADN/genética , ADN de Hongos/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Prueba de Complementación Genética , Hidroliasas/genética , Hidroliasas/metabolismo , Modelos Biológicos , Datos de Secuencia Molecular , Mutación Puntual , ARN de Hongos/genética , ARN de Hongos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Homología de Secuencia de Aminoácido , Transformación Genética , Regulación hacia ArribaRESUMEN
Cucurbita pepo L, comúnmente conocida como calabaza, se ha empleado en la medicina tradicional como antihelmíntica y diurética. Por su elevado porcentaje de aceite fijo en sus semillas, rico en ácidos grasos poliinsaturados, fitoesteroles, tocoferoles y carotenoides, este ha sido empleado en el tratamiento de enfermedades que involucran procesos inflamatorios como la hiperplasia prostática benigna...
Cucurbita pepo L, commonly known as pumpkin, has been used as antihelminthic and diuretic compound in the traditional herbal medicinal. Due to high oil percentage in its seeds, rich in polyunsaturated fatty acids, phytosterols, tocopherols and carotenoids, this oil has been used in the treatment of diseases involving inflammatory processes such as benign prostatic hyperplasia...
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Cucurbita pepo/uso terapéutico , Extractos VegetalesRESUMEN
NRPSs (non-ribosomal peptide synthetases) and PKSs (polyketide synthases) require post-translational phosphopantetheinylation to become active. This reaction is catalysed by a PPTase (4'-phosphopantetheinyl transferase). The ppt gene of Penicillium chrysogenum, encoding a protein that shares 50% similarity with the stand-alone large PPTases, has been cloned. This gene is present as a single copy in the genome of the wild-type and high-penicillin-producing strains (containing multiple copies of the penicillin gene cluster). Amplification of the ppt gene produced increases in isopenicillin N and benzylpenicillin biosynthesis. A PPTase-defective mutant (Wis54-PPT(-)) was obtained. It required lysine and lacked pigment and penicillin production, but it still synthesized normal levels of roquefortine. The biosynthesis of roquefortine does not appear to involve PPTase-mediated modification of the synthesizing enzymes. The PPT(-) mutant did not require fatty acids, which indicates that activation of the fatty acid synthase is performed by a different PPTase. Complementation of Wis54-PPT(-) with the ppt gene restored lysine biosynthesis, pigmentation and penicillin production, which demonstrates the wide range of processes controlled by this gene.
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Proteínas Bacterianas/metabolismo , Lisina/biosíntesis , Penicilinas/biosíntesis , Penicillium chrysogenum/enzimología , Procesamiento Proteico-Postraduccional , Transferasas (Grupos de Otros Fosfatos Sustitutos)/metabolismo , Proteínas Bacterianas/genética , Northern Blotting , Southern Blotting , Cromatografía Líquida de Alta Presión , Clonación Molecular , Ácidos Grasos/biosíntesis , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Genoma Fúngico/genética , Compuestos Heterocíclicos de 4 o más Anillos/metabolismo , Indoles/metabolismo , Penicillium chrysogenum/genética , Penicillium chrysogenum/metabolismo , Piperazinas/metabolismo , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genéticaRESUMEN
High penicillin-producing strains of Penicillium chrysogenum contain 6-14 copies of the three clustered structural biosynthetic genes, pcbAB, pcbC, and penDE [Barredo, J.L., Díez, B., Alvarez, E., Martín, J.F., 1989. Large amplification of a 35-kb DNA fragment carrying two penicillin biosynthetic genes in high penicillin producing strains of Penicillium chrysogenum. Curr. Genet. 16, 453-459; Smith, D.J., Bull, J.H., Edwards, J., Turner, G., 1989. Amplification of the isopenicillin N synthetase gene in a strain of Penicillium chrysogenum producing high levels of penicillin. Mol. Gen. Genet. 216, 492-497.] . The cluster is located in a 56.8 kb DNA region bounded by a conserved TGTAAA/T hexanucleotide that undergoes amplification in tandem repeats [Fierro, F., Barredo, J.L., Díez, B., Gutiérrez, S., Fernández, F.J., Martín, J.F., 1995. The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences. Proc. Natl. Acad. Sci. USA 92, 6200-6204; Newbert, R.W., Barton, B., Greaves, P., Harper, J., Turner, G., 1997. Analysis of a commercially improved Penicillium chrysogenum strain series: involvement of recombinogenic regions in amplification and deletion of the penicillin biosynthesis gene cluster. J. Ind. Microbiol. Biotechnol. 19, 18-27]. Transcriptional analysis of this amplified region (AR) revealed the presence of at least eight transcripts expressed in penicillin producing conditions. Three of them correspond to the known penicillin biosynthetic genes, pcbAB, pcbC, and penDE. To locate genes related to penicillin precursor formation, or penicillin transport and regulation we have sequenced and analyzed the 56.8 kb amplified region of P. chrysogenum AS-P-78, finding a total of 16 open reading frames. Two of these ORFs have orthologues of known function in the databases. Other ORFs showed similarities to specific domains occurring in different proteins and superfamilies which allowed to infer their probable function. ORF11 encodes a D-amino acid oxidase that might be responsible for the conversion of D-amino acids in the tripeptide L-alpha-aminoadipyl-L-cysteinyl-D-valine or other beta-lactam intermediates to deaminated by-products. ORF12 encodes a predicted protein with similarity to saccharopine dehydrogenases that seems to be related to biosynthesis of the penicillin precursor alpha-aminoadipic acid. A deletion mutant, P. chrysogenum npe10 lacking the entire AR including ORF12, shows a partial requirement of L-lysine for growth. ORF13 encodes a putative protein containing a Zn(II)2-Cys6 fungal-type DNA-binding domain, probably a transcriptional regulator. Although some of the ORFs in the AR may play roles in increasing penicillin production, none of the 13 ORFs other than pcbAB, pcbC, and penDE seem to be strictly indispensable for penicillin biosynthesis. The genes located in the P. chrysogenum AR have been compared with those found in the Aspergillus nidulans 50 kb DNA region adjacent to the penicillin gene cluster, showing no conservation between these two fungi.
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Familia de Multigenes , Penicilinas/biosíntesis , Penicillium chrysogenum/genética , Transcripción Genética , Secuencia de Aminoácidos , Aspergillus nidulans/genética , Secuencia de Bases , Biología Computacional , Elementos Transponibles de ADN , Amplificación de Genes , Orden Génico , Genes Fúngicos , Lisina/biosíntesis , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Penicillium chrysogenum/crecimiento & desarrollo , Filogenia , Sacaropina Deshidrogenasas/genética , Secuencias Repetidas en TándemRESUMEN
Se estudio la filtracion del lobenzaria a presion cosntante con el empleo de polipropileno como material filtrante. Se determinaron la resistencia de la torta y del material filtrante, asi como la compresibilidad del lobenzarit durante la filtracion. Los resultados muestran que las particulas del solido se deforman considerablemente bajo la influencia de la presion