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CIGB-552 is a synthetic peptide that interacts with COMMD1 and upregulates its protein levels. The objectives of this phase I study were safety, pharmacokinetic profile, evaluation of the lymphocytes CD4+ and CD8+ and preliminary activity in patients with advanced tumors. A 3 + 3 dose-escalation design with seven dose levels was implemented. Patients were included until a grade 3 related adverse event occurred and the maximum tolerated dose was reached. The patients received subcutaneous administration of CIGB-552 three times per week for 2 weeks. Single-dose plasma pharmacokinetics was characterized at two dose levels, and tumor responses were classified by RECIST 1.1. Twenty-four patients received CIGB-552. Dose-limiting toxicity was associated with a transient grade 3 pruritic maculopapular rash at a dose of 7.0 mg. The maximum tolerated dose was defined as 4.7 mg. Ten patients were assessable for immunological status. Seven patients had significant changes in the ratio CD4/CD8 in response to CIGB-552 treatment; three patients did not modify the immunological status. Stable disease was observed in five patients, including two metastatic soft sarcomas. We conclude that CIGB-552 at dose 4.7 mg was well tolerated with no significant adverse events and appeared to provide some clinical benefits.
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Antineoplásicos/administração & dosagem , Peptídeos Penetradores de Células/administração & dosagem , NF-kappa B/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Peptídeos Penetradores de Células/efeitos adversos , Peptídeos Penetradores de Células/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/metabolismo , Neoplasias/patologia , Projetos de Pesquisa , Resultado do TratamentoRESUMO
Growth Hormone Releasing Peptide-6 (GHRP-6) is a promising molecule (H-His1-d-Trp- Ala-Trp-d-Phe-Lys6-NH2) for the treatment of several diseases. Studies on the degradation pathways of this molecule under stressed conditions are needed to develop appropriate formulations. Degradation products (DPs) of GHRP-6, generated by heating in the dark at 60 °C with pH ranging from 3.0 to 8.0 and in presence of common buffers, were isolated by RP-HPLC and characterized by ESI-MS/MS. C-terminal deamidation of GHRP-6 was generated preferentially at pH 3.0 and 8.0. Hydrolysis and head-to-tail cyclization were favored at pH ranging from 6.0 to 7.0 in phosphate containing buffers. A DP with +12 Da molecular mass was presumably originated by the reaction with formaldehyde derived from some of the additives and/or elastomeric closures. Certain DPs derived from the acylation reaction of the tri- and di-carboxylic buffering species were favored at pH 3.0-6.0 and indicate that buffer components, including those "Generally Recognized as Safe", may potentially introduce chemical modifications and product heterogeneity. Nano LC-MS/MS analysis revealed GHRP-6 was also detected as a low-abundance species with Trp oxidized to 5-hydroxy, kynurenine, and N-formylkynurenine. The kinetics for the formation of the major degradation products was also studied by RP-HPLC.
Assuntos
Hormônio Liberador de Hormônio do Crescimento , Espectrometria de Massas em Tandem , Concentração de Íons de Hidrogênio , Cinética , OligopeptídeosRESUMO
ABSTRACT Objective: To describe our experience on a case series treated with minimal invasive techniques in spine surgery, with short-term follow-up and identify complications. Methods: A prospective analysis was performed on 116 patients operated on by the same team from September 2015 to June 2016. Evaluating the short-term follow-up we registered the surgical time, bleeding, complications, hospital stay, pre- and postoperatively neurological status, as well as scales of disability and quality of life. Demographic and surgical procedure data were analyzed with SPSS version 20 program. Results: A total of 116 patients with a mean age of 49.7 + 15.7 (21-85 years) underwent surgery being 76 (65%) with lumbar conditions and 37 (32%) with cervical conditions. The most common procedures were tubular discectomies (31), tubular bilateral decompression (17), lumbar MI-TLIFs (7), and anterior cervical discectomy and fusion (35). The mean blood loss was 50.6 cc, the hospital stay was 1.7 day, pre- and postoperative pain VAS were 7.4 % and 2.3%, respectively, pre- and postoperative Oswestry (ODI) were 64.6% and 13.1%, respectively, pre- and postoperative SF-36 of 37.8% and 90.3%. There were no major complications, except for a surgical wound infection in diabetic patient and three incidental durotomies, one of these being a contained fistula, treated conservatively. Conclusions: The current tendency towards minimally invasive surgery has been justified on multiple studies in neoplastic and degenerative diseases, with the preservation of the structures that support the spine biomechanics. The benefits should not replace the primary objectives of surgery and its usefulness depends on the skills of the surgeon, pathology and the adequate selection of the techniques. We found that the tubular access allows developing techniques such as discectomy, corpectomy and fusion without limiting exposure, avoiding manipulation of adjacent structures, reducing complications and being feasible in a public hospital.
RESUMO Objetivo: Descrever nossa experiência em uma série de casos tratados por técnicas minimamente invasivas de cirurgia da coluna, o acompanhamento a curto prazo e identificar complicações. Métodos: Realizou-se análise prospectiva de 116 pacientes operados pela mesma equipe, de setembro de 2015 até junho de 2016. Avaliando o acompanhamento a curto prazo, foram registrados tempo cirúrgico, hemorragia, complicações, estadia hospitalar, estado neurológico pré e pós-operatório, além de escalas de incapacidade e qualidade de vida. Os dados demográficos e sobre o procedimento cirúrgico foram analisados com o programa SPSS versão 20. Resultados: Um total de 116 pacientes com média de idade de 49,7 + 15,7 (21 a 85 anos) foram operados, sendo 76 (65%) com afecção lombar e 37 (32%) com afecção cervical. Os procedimentos mais comuns foram discotomias tubulares (31), descompressão bilateral tubular (17), MI-TLIF (7) lombares; discotomia e artrodese anterior (35). O sangramento médio foi de 50,6 cm3, o tempo de hospitalização foi 1,7 dia, a escala EVA pré-cirúrgica foi 7,4 e a pós-cirúrgica 2,3, Oswestry (ODI) pré-cirúrgico de 64,6% e pós-cirúrgico de 13,1%, SF-36 pré-cirúrgico de 37,8% e pós-cirúrgico de 90,3%. Não houve grandes complicações, exceto uma infecção da ferida cirúrgica em paciente diabética e três durotomias incidentais um dos pacientes com fístula, uma delas contida, tratada de modo conservador. Conclusões: A tendência atual da cirurgia minimamente invasiva tem sido justificada em vários estudos sobre neoplasia e doenças degenerativas, preservando as estruturas da biomecânica da coluna vertebral. Os benefícios não devem substituir os objetivos primários e sua utilidade depende das habilidades do cirurgião, da patologia e do uso seletivo das técnicas. Constatamos que o acesso tubular permite desenvolver a técnica de discotomia, fusão e corpectomia sem limite de exposição, evitando manipulação de estruturas adjacentes, reduzindo as complicações e sendo viável em hospitais públicos.
RESUMEN Objetivo: Describir nuestra experiencia en una serie de casos tratados mediante técnicas mínimamente invasivas en cirugía de columna, su seguimiento a corto plazo e identificar las complicaciones. Métodos: Se realizó un análisis prospectivo en 116 pacientes intervenidos por el mismo equipo desde septiembre de 2015 a junio de 2016. Evaluando el seguimiento a corto plazo, se registró tiempo quirúrgico, sangrado, complicaciones, estancia hospitalaria, estado neurológico pre y post operatorio además de escalas de discapacidad y calidad de vida. Los datos demográficos y del procedimiento quirúrgico fueron analizados con el programa SPSS versión 20. Resultados: Un total de 116 pacientes con edad promedio de 49,7 + 15,7 (21 a 85 años), fueron intervenidos siendo 76 (65%) patologías lumbares y 37 (32%) cervicales. Los procedimientos más comunes fueron discectomías tubulares (31), descompresión bilateral tubular (17), MI-TLIF (7) lumbares; discectomía y artrodesis anterior (35). El promedio de sangrado fue 50,6 cc, estancia hospitalaria 1,7 día, escala EVA prequirúrgica 7,4 y posquirúrgica 2,3, Oswestry (ODI) prequirúrgico 64,6% y posquirúrgico 13,1%, SF-36 prequirúrgico 37,8% y posquirúrgico 90,3%. No hubo complicaciones mayores, excepto una infección de herida quirúrgica en paciente diabética y 3 durotomías incidentales, una de estas con fístula contenida, de manejo conservador. Conclusiones: La tendencia actual de la cirugía mínimamente invasiva se ha justificado en múltiples estudios en patología tumoral y degenerativa, con la conservación de estructuras para biomecánica de la columna. Los beneficios no deben reemplazar los objetivos primarios y su utilidad depende de las habilidades del cirujano, la patología, y el uso selectivo de las técnicas. Encontramos que el acceso tubular permite desarrollar la técnica de discectomía, fusión y corpectomía sin limitar la exposición, evitando manipulación de estructuras adyacentes, disminuyendo complicaciones y siendo factible en un hospital público.
Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Doenças da Coluna Vertebral/cirurgia , Estudos Prospectivos , Resultado do TratamentoRESUMO
Growth hormone releasing peptide, GHRP-6, a hexapeptide (His-(D-Trp)-Ala-Trp-(D-Phe)-Lys-NH2, MW = 872.44 Da) that belongs to a class of synthetic growth hormone secretagogues, can stimulate growth hormone secretion from somatotrophs in several species including humans. In the present study, we demonstrate that GHRP-6 dispersed in aqueous solution, at pH 7.0, room temperature of 22 °C, is able to form long nanotubes, which is evidenced by combining small angle X-ray scattering (SAXS), transmission electron microscopy and molecular dynamics simulation results. Such nanotubes possess inner and outer cross-sections equal to 6.7(2) nm and 13.4(5) nm, respectively. The mechanism of peptide self-assembly was determined by molecular dynamics simulations revealing that the peptides self-assemble like amphiphilic molecules in aqueous solution in a partially interdigitated structure. In this case, the position of the positively charged amino terminus is located at the peptide-water interface, whereas the neutral NH2-capped carboxy terminus remains buried at the hydrophobic core. In contrast, the long side chain of Lys-6 stretches out of the hydrophobic core positioning its positive charge near the cylinder surface. The peptide configuration in the nanotube wall comes from the interplay between the hydrophobic interactions of the aromatic side chains of GHRP-6 and the electrostatic repulsion of its cationic charges. On increasing the peptide concentration, the long nanotubes self-arrange in solution displaying a bi-dimensional hexagonal-like packing in the SAXS curves, with a center-to-center distance of â¼15 nm. Further, we also show that the nanostructure formed in solution is quite stable and is preserved following transfer to a solid support.
Assuntos
Nanotubos/química , Oligopeptídeos/química , Sequência de Aminoácidos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Oligopeptídeos/metabolismo , Água/químicaRESUMO
Introducción. La familia de sarcomas de Ewing incluye el sarcoma de Ewing óseo, el tumor neuroectodérmico primitivo, el sarcoma de Ewing extraóseo y el tumor de Askim (sarcoma de Ewing de la pared torácica). Los sitios más comunes de estos tumores son tórax y extremidades. Estos tumores malignos surgen del hueso o de tejidos blandos. Histológicamente, se caracterizan por alta celularidad de pequeño tamaño, redondas, azules y con tendencia a formar estructuras rosetoides. Caso clínico. Se presentó el caso de un adolescente de 14 años de edad que, tres meses previos a su ingreso, inició con cefalea fronto-parietal izquierda con irradiación hacia el globo ocular. Al examen neurológico se encontró proptosis y disminución de la agudeza visual, además de atrofia papilar. Se realizó una tomografía computarizada de cráneo, donde se identificó una lesión intraorbitaria izquierda y otra parietotemporal ipsilateral. Se realizó la exéresis tumoral, reportando positividad para marcadores de tumor neuroectodérmico primitivo, vimentina y CD99. Conclusiones. El sarcoma de Ewing es extremadamente raro a nivel de la órbita. Sin embargo, es prudente considerarlo como diagnóstico diferencial en lesiones de esta región, ya que el pronóstico depende de la precisión diagnóstica temprana.
Background. The Ewing sarcoma family includes Ewing bone sarcoma, primitive neuroectodermal tumor, extraosseous Ewing's sarcoma, and Askim tumor (Ewing sarcoma of the chest wall). The most common sites of these tumors are chest and limbs. These malignancies arise from bone or soft tissues. Histologically, it is characterized by high cellularity, small, round, blue and with a tendency to form rosette structures. Case report. We report the case of a 14-year-old patient whose evolution began 3 months before admission with left frontoparietal headache radiating to the eyeball. During neurological examination, proptosis and decreased visual acuity were found, as well as papillary atrophy. Cranial computed tomography identifed a left intraorbital injury and another ipsilateral parietotemporal. Tumor exeresis was performed, reporting positive for primitive neuroectodermal tumor markers, vimentin and CD 99. Conclusions. Ewing sarcoma is extremely rare at the orbital level: however, it is prudent to consider this tumor as a differential diagnosis in lesions of this region. Prognosis depends on early diagnostic accuracy.
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Introducción. Las malformaciones aneurismáticas del polígono de Willis comprenden un raro grupo de anomalías congénitas que se presentan en edades pediátricas. Son causa importante de morbimortalidad en este grupo de edad; en consecuencia, el manejo de estas lesiones es complejo y potencialmente letal, y puede plantear problemas para el paciente y su tratamiento. Caso clínico. Presentamos el caso de una niña de 10 años que inició de manera súbita con síncope neurogénico y crisis convulsivas tónico-clónicas generalizadas. Al llegar a urgencias, se le realizó una tomografía donde se identificó hemorragia subaracnoidea Fisher II. En la angiografía cerebral de 4 vasos se observó una lesión sacular del ápex carotideo, de aproximadamente 5.1 x 7.2 mm, con cuello visible y domo dirigido hacia la parte cefálica y hacia la parte frontal. Se le realizó craneotomía fronto-pterional derecha. Durante el transquirúrgico, se llevaron a cabo un ultrasonido pre-clipaje, que identificó la lesión aneurismática, y uno post-clipaje, para verificar la permeabilidad de las ramas distales al clipaje. Conclusiones. Las malformaciones aneurismáticas en la edad pediátrica son extremadamente raras. Por ello, métodos como la endoscopia y la sonografía transoperatoria y postoperatoria son de gran utilidad, ya que evidencian detalles que en ocasiones los estudios de imagen convencionales no revelan. Todo esto condiciona un procedimiento con menor riesgo de morbimortalidad para este tipo de pacientes.
Background. Aneurysm malformations of the circle of Willis comprise a rare group of congenital anomalies that occur during the pediatric age and are a major cause of morbidity and mortality in this age group. Consequently, management of these lesions is complex and potentially lethal and may pose problems for the patient and affect their treatment. Case report. We report the case of a 10-year-old girl who had a sudden onset of neurogenic syncope and tonic-clonic seizures. After arriving at the emergency room, she underwent a CT scan, identifying a Fisher II subarachnoid hemorrhage. Four-vessel cerebral angiography identified apex saccular carotid injury ~5.1 x 7.2 mm with visible neck and dome partially cephalic and partially frontal. Right frontopterional craniotomy was performed and preclipping during trans-surgical ultrasound was performed, identifying the aneurysmal lesion and post-clipping to verify patency of the distal branches to clipping. Conclusions. Aneurysmal malformations in children are extremely rare. For this reason, methods such as endoscopy, trans- and postoperative ultrasound are very useful. These procedures sometimes reveal details that conventional imaging studies do not, determining use of a procedure with less risk of morbidity and mortality for these patients.
RESUMO
A successful parenteral formulation can be developed by studying stability and compatibility of biopharmaceuticals as a function of solution composition. Here, we evaluate the influence of pH, buffers, ionic strength, protein concentration and presence of excipients on recombinant human epidermal growth factor (rhEGF) stability. The stability was accessed by reversed-phase high performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC-HPLC), enzyme-linked immunosorbent assay (ELISA), Far-UV circular dichroism (CD) and light scattering. The overall maximal stability was obtained in pH near to 7.0 in phosphate, Tris and histidine buffers as the results of the different methods revealed. The CD results revealed that this protein is stable in an extensive pH range. Aggregation of rhEGF was minimized at pH values ranged from 6.0 to 8.0 as indicated the SEC-HPLC and light scattering results. Nor the ionic strength neither the rhEGF concentration had significant effect on the reaction rate constants. Most rhEGF-excipient instability occurs among this protein and reducing sugars. Polymers like poly(ethylene glycol) (PEG) and polysorbates increased methionine oxidation. The rhEGF oxidation and deamidation were the most common degradation pathways. This research identified critical solution factors to be considered for the development of a successful rhEGF parenteral formulation.
Assuntos
Fator de Crescimento Epidérmico/química , Excipientes/química , Soluções Tampão , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Concentração Osmolar , Nutrição Parenteral , Proteínas Recombinantes/químicaRESUMO
PURPOSE: The aim of this study was to assess the use of a new medical device to elevate depressed skull fractures (DSFs) in newborns and minor infants. METHODS: Nine patients (ranging from 1 day to 9 months of age) with simple DSF underwent skull elevation by a new elevator medical device. This medical device comprises two elements: a pediatric resuscitator (CPR mask) connected to a 50-ml syringe. Pediatric CPR face mask is placed on the depressed region and negative pressure is generated through syringe plunger elevation until fracture reduction is observed. RESULTS: Fracture reduction was confirmed in eight of nine patients by computed tomography scan without underlying brain damage and associated complications. Skull asymmetry was eliminated recovering normal shape. Up to now, there are no neurological concerns. Another treatment was chosen to be applied for one patient who did not respond to manipulation. CONCLUSION: The new device is a safe, affordable, and effective choice in the treatment of simple depressed skull fractures in newborns and minor infants.
Assuntos
Descompressão/instrumentação , Fratura do Crânio com Afundamento/terapia , Desenho de Equipamento , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Radiografia , Fratura do Crânio com Afundamento/diagnóstico por imagem , Resultado do TratamentoRESUMO
BACKGROUND: Multiple myeloma is a plasmatic cell neoplasm that is characterized by skeletal destruction, renal failure, anemia and hypercalcemia. The skull plasmacytomas represent less than 1% of the head and neck tumors, they can be the primary lesion or occur as a secondary manifestation of multiple myeloma in 20-30% of the patients, or they can even manifest several years later after the diagnosis of plasmacytoma. Although some of the lesions may be surgically accessible, the aggressive natural behavior will complicate the evolution of the patients. We present two cases of Mexican women with intracranial plasmacytomas, one of them associated with multiple myeloma. CLINICAL CASES: The first case was a 24 year-old woman diagnosed with a multiple myeloma with plasmacytic-plasmablastic bone infiltration that was removed in 90%. She presented a local recurrence that required a second intervention for removal. The second case was a 62 year-old female with a malignant intracranial tumor of plasma cells that was totally resected. Both patients received adjuvant treatment based on chemotherapy and radiation therapy with favorable results. The patients died at 5 and 1.5 years respectively due to renal failure secondary to systemic disease. CONCLUSIONS: We propose chemotherapy and radiation therapy as an essential part of treatment for this condition, as the aggressive behavior of the neoplasms can complicate the evolution, despite being surgically accessible.
Antecedentes: el mieloma múltiple es una neoplasia de células plasmáticas caracterizada por destrucción ósea, insuficiencia renal, anemia e hipercalcemia. Los plasmacitomas de los huesos del cráneo representan menos de 1% de los tumores de cabeza y cuello. Se manifiestan como lesión primaria o secundaria a mieloma múltiple en 20-30%, incluso pueden aparecer varios años después del diagnóstico. Los autores comunicamos dos casos de pacientes mexicanas con lesiones plasmocíticas intracraneales, asociadas con mieloma múltiple.Casos clínicos: el primer caso es el de una paciente de 24 años de edad, con diagnóstico de mieloma múltiple e infiltración ósea que fue extirpado en 90%. Experimentó una recidiva local que requirió otra intervención para su remoción. El segundo caso es el de una mujer de 62 años de edad con un tumor intracraneal de células plasmáticas que se resecó en su totalidad. Ambas recibieron terapia adyuvante con quimio y radioterapia con resultados favorables. Las pacientes fallecieron a los 5 y 1.5 años, respectivamente, por insuficiencia renal como consecuencia de la enfermedad sistémica. Conclusiones: se propone a la quimioterapia y radioterapia como parte esencial del tratamiento de este tumor porque su comportamiento natural agresivo puede complicar la evolución, a pesar de ser accesibles quirúrgicamente.
Assuntos
Encéfalo/patologia , Osso Frontal/patologia , Mieloma Múltiplo/patologia , Neoplasias Orbitárias/patologia , Plasmocitoma/patologia , Complicações Neoplásicas na Gravidez/patologia , Neoplasias Cranianas/patologia , Quimioterapia Adjuvante , Terapia Combinada , Irradiação Craniana , Craniotomia , Evolução Fatal , Feminino , Osso Frontal/cirurgia , Humanos , Falência Renal Crônica/etiologia , Meninges/patologia , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Neoplasias Orbitárias/cirurgia , Osteólise/etiologia , Osteólise/patologia , Plasmocitoma/irrigação sanguínea , Plasmocitoma/complicações , Plasmocitoma/terapia , Gravidez , Complicações Neoplásicas na Gravidez/terapia , Radioterapia Adjuvante , Neoplasias Cranianas/complicações , Neoplasias Cranianas/terapia , Adulto JovemRESUMO
BACKGROUND: It is estimated that 15% of couples living in industrialized countries are infertile, ie have failed to conceive, reproductive age, after 12 months ormore of regular intercourse without contraception. During the past decade has increased the demand for fertility treatments because they believe are moreeffective now. OBJECTIVE: To unify the therapeutic approach and service to patients and set a precedent for a Mexican Official Standard respect and support for the legislation of these procedures. METHOD: Consensus by technical experts group panel with the participation of 34 national centers accredited for use in assisted reproduction. He organized seven workshops with the following themes: 1) selection of patients for assisted reproduction treatment, 2) schemes controlled ovarian stimulation for assisted reproduction techniques of high complexity, 3) preparation and egg retrieval technique, 4) transferembryo; 5) luteal phase supplementation; 6) indications and techniques of cryopreservation and 7) informed consent. Each table had a coordinator who wrote and presented the findings to the full, it made a number of observations until they reached unanimity of criteria, which are reflected in this document. RESULTS: Patient selection for assisted reproduction techniques is the first step of the process. Proper selection lead to success, in the same way that a bad pick up for failure. In the case of egg donation the most important recommendation is that only one to two embryos transferred in order to reduce multiple pregnancy rates and maintaining high pregnancy rates.