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1.
Molecules ; 28(19)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37836772

RESUMO

Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by the World Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutant-type (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs.


Assuntos
Fluoroquinolonas , Quinolonas , Fluoroquinolonas/farmacologia , Fluoroquinolonas/química , Escherichia coli/metabolismo , Simulação de Acoplamento Molecular , Antibacterianos/química , Quinolonas/química , DNA Girase/química , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana
2.
Cureus ; 15(7): e42013, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37593282

RESUMO

Colonic varices are a rare condition primarily caused by portal hypertension associated with conditions such as cirrhosis or hepatocellular carcinoma. Idiopathic cases are even rarer, with less than 50 cases with a pan-colonic affection reported in the literature. Males are more commonly affected, with an average age of 41 years. Colonic varices can involve the entire colon in idiopathic cases and are often familial. Gastrointestinal bleeding is the main symptom, ranging from mild to life-threatening. Diagnosis is typically made through colonoscopy, which reveals dilated bluish vascular tracts. Treatment involves fluid IV resuscitation and controlling hemorrhage through various methods such as endoscopic procedures. Correction of the underlying cause is essential in cases of portal hypertension. Recurrent or unstable cases may require colon resection. On this occasion, we present the case of a female patient who experienced profuse lower gastrointestinal bleeding. The patient's colonoscopy revealed the presence of varices throughout the entire length of the colon, with the only recent bleeding site being in the hemorrhoidal tissue. Therefore, a hemorrhoidectomy was performed to carry out an effective and less invasive therapeutic procedure than a colectomy with an excellent postoperative evolution.

3.
Pharmaceutics ; 16(1)2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38258053

RESUMO

Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.

4.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443548

RESUMO

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models-S. cerevisiae, five cancer cell lines, and the parasite L. mexicana-were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.


Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Ciclopropanos/síntese química , Ciclopropanos/farmacologia , Leishmaniose/tratamento farmacológico , Animais , Antiprotozoários/química , Antiprotozoários/uso terapêutico , Linhagem Celular , Técnicas de Química Sintética , Ciclopropanos/química , Ciclopropanos/uso terapêutico , Desenho de Fármacos , Humanos , Leishmania/efeitos dos fármacos , Relação Estrutura-Atividade
5.
Rev Peru Med Exp Salud Publica ; 37(3): 431-437, 2020 Dec 02.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-33295544

RESUMO

OBJECTIVES: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. MATERIALS AND METHODS: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. RESULTS: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. CONCLUSIONS: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.


OBJETIVOS: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. MATERIALES Y MÉTODOS: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. RESULTADOS: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. CONCLUSIONES: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.


Assuntos
Bactérias , Produtos Biológicos , Bactérias/isolamento & purificação , Produtos Biológicos/análise , Produtos Biológicos/normas , Indústria Farmacêutica , Equador , Marketing
6.
Rev. Fund. Educ. Méd. (Ed. impr.) ; 23(5): 243-249, sept.-oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-197067

RESUMO

INTRODUCCIÓN: El contexto actual demanda incorporar el manejo de situaciones de catástrofes en la formación médica. Se presenta una experiencia original en la enseñanza de emergencias y desastres, en la carrera de medicina, con uso de metodologías didácticas activas. SUJETOS Y MÉTODOS: El plan didáctico del curso se diseñó incorporando el uso de metodologías de trabajo colaborativo (desarrollo de casos, team based learning, juego de roles), uso de tecnologías de información y comunicación, visitas sobre el terreno y simulaciones. Para cada actividad docente, se elaboró material y pautas de evaluación correspondientes. El curso se evaluó con las calificaciones de los estudiantes, su grado de satisfacción y sus comentarios. Adicionalmente, se realizó un análisis de fortalezas y debilidades por parte del equipo docente, planteándose un plan de mejoras. RESULTADOS: Las calificaciones del curso (escala de 1 a 7; n = 58) fueron altas (media: 6,1; rango: 5,7-6,5). Se observó un alto grado de satisfacción con las estrategias docentes utilizadas (valoraciones del 85-95%). Según el parecer de los estudiantes, se lograron los objetivos de aprendizaje en un 88% (trabajo en equipo) y 93% (conceptualización y aplicación). CONCLUSIÓN: El uso de metodologías activas motiva y favorece el aprendizaje, lo que se traduce en altas calificaciones y grado de satisfacción de los estudiantes, así como una buena percepción de utilidad respecto de su futuro desarrollo profesional


INTRODUCTION: The current context demands to incorporate the management of catastrophe situations in medical education. The original experience utilizing active teaching methodologies in a new course of emergencies and disasters in the medical undergraduate formation is presented. SUBJECTS AND METHODS: The course's didactic plan was designed incorporating the use of collaborative work methodologies (case development, team based learning, role play), use of information and communication technologies, field visit and simulations. For each teaching activity, material and corresponding evaluation guidelines were developed. The course was evaluated with the students' qualifications, their degree of satisfaction and their comments. Additionally, an analysis of strengths and weaknesses was carried out by the teaching team; considering an improvement plan. RESULTS: The course qualifications (scale 1 to 7; n = 58) were highly acceptable (average: 6.1; range: 5.7-6.5). A high degree of satisfaction was observed with the teaching strategies used (valuations between 85-95%). In the opinion of the students, the learning objectives were achieved between 88% (teamwork) and 93% (conceptualization and application). CONCLUSION: The use of active methodologies motivates and favors learning, resulting in high qualifications and student's satisfaction, as well as a good perception of usefulness regarding their future professional development


Assuntos
Humanos , Educação Médica/métodos , Avaliação Educacional , Emergências , Práticas Interdisciplinares , Tecnologia da Informação , 28574/métodos , Competência Clínica , Tratamento de Emergência , Satisfação Pessoal , Desempenho Acadêmico
7.
Rev. peru. med. exp. salud publica ; 37(3): 431-437, jul-sep 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1145013

RESUMO

RESUMEN Objetivos: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. Materiales y métodos: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. Resultados: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. Conclusiones: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.


ABSTRACT Objectives: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. Materials and methods: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. Results: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. Conclusions: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.


Assuntos
Bactérias , Resistência Microbiana a Medicamentos , Comércio , Preparações de Plantas , Economia , Bactérias/isolamento & purificação , Produtos Biológicos , Produtos Biológicos/análise , Produtos Biológicos/normas , Marketing , Indústria Farmacêutica , Equador , Escherichia coli , Fungos , Antibacterianos
8.
Nanomaterials (Basel) ; 10(5)2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438544

RESUMO

Excipients represent the complement of the active principle in any pharmaceutical form. Their function is to provide stability, protection, and to ensure absorption of the drug and acceptability in patients. Cellulose is a conventional excipient in many pharmaceutical solid dosage products. Most of the sources used to extract microcrystalline cellulose come from cotton or wood, which are expensive and in high demand from other industries. As plants are considered the main source of excipient production, we have taken advantage of the biodiversity of Ecuador to evaluate microcrystalline cellulose extracted from borojó (Alibertia patinoi), a native plant, as an excipient for solid dosage formulations. The method of choice for tablet manufacturing was direct compression since it is a conventional fabrication method in the pharmaceutical industry. First, we performed scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) in order to compare the structure and characteristics of the extracted cellulose with two reference commercial cellulose materials. Second, we performed quality tests to evaluate the use of the isolate as an excipient including fluidity, hardness, friability, and disintegration. Compared with commercial and microcrystalline cellulose, the extracted cellulose from the native plant showed comparable characteristics and is consequently a potential excipient that could be used in the pharmaceutical industry. Last, we performed a dissolution test in which we concluded that all tablets have a short release time of active principle.

9.
Immunopharmacol Immunotoxicol ; 41(1): 140-149, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30714433

RESUMO

Context: Influenza is a severe, life-threatening viral disease that can be prevented by vaccination. However, the anti-influenza human vaccine failed to show the required efficacy both in infants under 5 years old and in the elder population, who are among those with the highest risk of developing severe complications after influenza infection. Therefore, it is of high importance to improve the vaccine efficacy and ensure its safety in these susceptible populations. GK-1, a novel 18-aa peptide adjuvant, has been proved to increase the immunogenicity of the human influenza vaccine in both young and aged mice. Objective: A preclinical study of the toxicity profile of GK-1 following the World Health Organization guidelines to support its use was herein conducted. Material and methods: GK-1 was synthetically produced following Good Manufacturing Practices. The toxicological evaluation of GK-1 peptide was performed in rats after repeated dose-ranging trials by the subcutaneous route. The mutagenic potential of GK-1 was assessed by the micronucleus, chromosomal aberration, and Ames tests, in accordance with OECD Guidelines. Results: GK-1 did not show toxic effects at doses up to 12.5mg/kg, corresponding to 25 times the dose intended for human use. No indications of mutagenic potential were observed. GK-1 after dermal administration was well tolerated locally. Conclusion: The efficacy of GK-1 to improve influenza vaccine protection, along with the absence of toxicity and mutagenicity, as reported herein, support the evaluation of this peptide in a clinical trial as a novel adjuvant for human use.


Assuntos
Adjuvantes Imunológicos/toxicidade , Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA , Vacinas contra Influenza/imunologia , Peptídeos Cíclicos/toxicidade , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Influenza Humana/prevenção & controle , Injeções Subcutâneas , Masculino , Testes de Mutagenicidade , Peptídeos Cíclicos/imunologia , Ratos Wistar , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Testes de Toxicidade Crônica
10.
Toxicol In Vitro ; 33: 16-22, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26911729

RESUMO

Casiopeína III-Ea (Cas III-Ea(1)) is a copper complex with antiproliferative and antitumor activities, designed to act via alternative mechanisms of action different from Cisplatin. This compound has also been well characterized in preclinical test and pharmacokinetic analysis, being a good candidate for clinical phases. Since very little is known about the processes of biotransformation of therapeutic metal based drugs, this paper report the first approach to the study of the interaction between metal complex Cas III-Ea and cytochromes P450 with the aim to find out possible biotransformation pathways for this complexes and feasible drug-drug interactions. Results showed that Cas III-Ea is a strong irreversible competitive inhibitor of CYP1A1 (IC50 = 7.5 ± 1.0 µM; Ki = 240 nM). The magnitude of values indicate that it is necessary to be taken into account such effect when analyzing possible drug interactions with these new drugs in order to prevent adverse reactions derived from this inhibition.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Fenantrolinas/farmacologia , Animais , Cinética , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Ratos Wistar
11.
Trials ; 16: 193, 2015 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-25927183

RESUMO

BACKGROUND: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. METHODS: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra- and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra- and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications. TRIAL REGISTRATION: Registered on 5 June 2014 with identification no. NCT02158923 .


Assuntos
Abdome/cirurgia , Pressão Positiva Contínua nas Vias Aéreas , Pneumopatias/prevenção & controle , Pulmão/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Respiração Artificial/métodos , Protocolos Clínicos , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Masculino , Assistência Perioperatória , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Projetos de Pesquisa , Respiração Artificial/efeitos adversos , Espanha , Fatores de Tempo , Resultado do Tratamento
12.
Sci Rep ; 4: 6743, 2014 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-25339199

RESUMO

The antioxidant and hepatoprotective effects of Heterotheca inuloides have been reported before, nevertheless its use as a possible chemopreventive agent has not been documented. The aim of this study was to evaluate the mutagenic and antimutagenic activities of H. inuloides extracts using the Ames test. Both, the methanolic and acetonic extracts, were mutagenic in the TA98 but not in TA100 or TA102 strains. On the other hand, the methanolic extract reduced the mutagenicity of norfloxacin, benzo[a]pyrene and 2-aminoanthracene. Quercetin, one of the main components in the methanolic extract, also presented a mutagenic/antimutagenic dual effect and is an inhibitor of Cytochrome P450 (CYP) 1A. The antigenotoxic properties of H. inuloides could be due to the antioxidant properties previously reported and to its CYP inhibitory effect mediated by quercetin. Further studies with in vivo systems will afford information about H. inuloides beneficial and detrimental properties.


Assuntos
Antimutagênicos/administração & dosagem , Asteraceae/química , Mutagênese/efeitos dos fármacos , Quercetina/administração & dosagem , Antimutagênicos/química , Antioxidantes/química , Citocromo P-450 CYP1A1/genética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/genética , Quercetina/química , Quercetina/genética , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
13.
J Org Chem ; 79(20): 9647-54, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25238507

RESUMO

On the basis of previous conformational and configurational studies of 4-aryl-substituted cyclophosph(on)ates derived from d-xylofuranose derivatives, wherein it was proposed that the anomeric effect is involved in the spontaneous isomerization of the P atom and the C4 carbon, and consequently, this unusual behavior was associated with the cleavage of the HepDirect prodrugs. We synthesized an analogous series of 2-amino-2-oxo-1,3,2-dioxaphosphorinanes and performed a conformational and configurational analysis in solution and the solid state followed by an examination of their mutagenic activity. The results showed that the 2-amino-2-oxo-1,3,2-dioxaphosphorinanes with the largest mutagenic activity contain either a 4-methoxyphenyl or 4-fluorophenyl group at C4 carbon and presented a major chair conformation, which is prone to weaken the C4-O3 bond via the anomeric effect and facilitates the cleavage for the release of the biologically active metabolite.


Assuntos
Ciclofosfamida/química , Compostos Organofosforados/química , Pró-Fármacos/química , Isomerismo , Modelos Moleculares , Conformação Molecular
14.
Surg Today ; 44(1): 34-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23686591

RESUMO

PURPOSE: To assess the functional outcomes and quality of life in patients with laparoscopic total colectomy for slow-transit constipation (STC). METHODS: All patients undergoing laparoscopic colectomy with ileorectal anastomosis for colonic inertia at two referral centers were analyzed. Their preoperative, intraoperative and postoperative details were recorded with a one-year follow-up. Their quality of life was assessed using the SF-36 questionnaire. RESULTS: Between 2004 and 2007, 710 patients were evaluated. Eight female patients (1.1 %) fulfilled the criteria for STC without obstructive defecation syndrome. Their mean age was 38 years ± 15 (range from 22 to 62). The conversion rate was 12.5 %. The morbidity rate was 37.5 %, and mortality was nil. The preoperative abdominal pain was 6.6 ± 0.3 and had decreased to 3.6 ± 2.3 postoperatively (P = 0.008). At 1 year, the defecation frequency per week had increased from 0.84 ± 0.24 to 6.75 ± 3.4 (P = 0.001). Three patients developed nocturnal leakage (37.5 %). Eighty-eight percent of the patients recommend the procedure. All parameters of the SF-36 questionnaire had improved at the one-year follow-up examination. CONCLUSION: Laparoscopic colectomy for slow-transit constipation is safe and increased the number of evacuations per week. Although nocturnal leakage may occur, these patients experience improvements in their quality of life.


Assuntos
Colectomia/métodos , Constipação Intestinal/cirurgia , Laparoscopia/métodos , Adulto , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Colectomia/efeitos adversos , Constipação Intestinal/fisiopatologia , Defecação , Feminino , Seguimentos , Motilidade Gastrointestinal , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
15.
Mutagenesis ; 28(6): 645-51, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23956140

RESUMO

Niclosamide produces genotoxic effects, such as point mutations in Salmonella sp., sperm-head abnormalities in mice and clastogenic effects in human lymphocytes in vitro and in vivo. As cytochrome P450 could be involved in the bioactivation of niclosamide, we investigated which subfamily was involved. We used liver microsomal fractions from rats treated with phenobarbital/ß-naphthoflavone (PB/ß-NF), benzo[a]pyrene (BaP) or cyclohexanol, which are known to induce different cytochrome P450 subfamilies, such as CYP2B, CYP1A1, CYP1A2 and CYP2E1. We also inhibited CYP1A and CYP2E using α-NF and diethyldithiocarbamate to identify the cytochrome P450 involved. Liver-S9 fractions obtained from PB/ß-NF- and BaP-treated rats significantly increased the number of revertants induced by niclosamide, while the CYP1A1 inhibitor α-NF decreased the number of revertants. The incubation of niclosamide with CYP1A1 Supersomes™ increased the number of revertants, suggesting that CYP1A1 is responsible for the bioactivation of niclosamide. Nitroreduction is also involved in niclosamide bioactivation, as the nitroreductase-deficient strain YG7132 did not respond to the niclosamide treatment. Our findings indicated that a metabolite, derived from the action of CYP1A1 and a nitroreduction-reaction process, has a key role in the bioactivation of niclosamide.


Assuntos
Proteínas de Bactérias/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Mutagênicos/metabolismo , Niclosamida/metabolismo , Nitrorredutases/metabolismo , Animais , Benzoflavonas/farmacologia , Biotransformação , Citocromo P-450 CYP1A1/antagonistas & inibidores , Masculino , Microssomos Hepáticos/enzimologia , Testes de Mutagenicidade , Mutagênicos/farmacologia , Niclosamida/farmacologia , Oxirredução , Ratos , Ratos Wistar , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/enzimologia , Salmonella typhimurium/genética
16.
Sensors (Basel) ; 12(6): 7598-613, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22969363

RESUMO

The flow of air generated by a new design of air assisted sprayer equipped with two axial fans of reversed rotation was analyzed. For this goal, a 3D sonic anemometer has been used (accuracy: 1.5%; measurement range: 0 to 45 m/s). The study was divided into a static test and a dynamic test. During the static test, the air velocity in the working vicinity of the sprayer was measured considering the following machine configurations: (1) one activated fan regulated at three air flows (machine working as a traditional sprayer); (2) two activated fans regulated at three air flows for each fan. In the static test 72 measurement points were considered. The location of the measurement points was as follow: left and right sides of the sprayer; three sections of measurement (A, B and C); three measurement distances from the shaft of the machine (1.5 m, 2.5 m and 3.5 m); and four measurement heights (1 m, 2 m, 3 m and 4 m). The static test results have shown significant differences in the module and the vertical angle of the air velocity vector in function of the regulations of the sprayer. In the dynamic test, the air velocity was measured at 2.5 m from the axis of the sprayer considering four measurement heights (1 m, 2 m, 3 m and 4 m). In this test, the sprayer regulations were: one or two activated fans; one air flow for each fan; forward speed of 2.8 km/h. The use of one fan (back) or two fans (back and front) produced significant differences on the duration of the presence of wind in the measurement point and on the direction of the air velocity vector. The module of the air velocity vector was not affected by the number of activated fans.

17.
Rev. univ. psicoanál ; 9: 211-228, nov. 2009.
Artigo em Espanhol | BINACIS | ID: bin-124444

RESUMO

El presente trabajo tiene como objetivo determinar cuáles fueron los modos de compensación de la psicosis en Van Gogh. Se busca indagar los recursos que posibilitaron al artista remediar provisoriamente, la carencia simbólica. Como fuente biográfica principal se utiliza el intercambio epistolar entre el pintor y su hermano Theo. El análisis que se efectúa es de carácter exploratorio, bajo los aportes de Jaques Lacan. Se procede a examinar la categoría de fenómeno elemental para interrogase sobre la alucinación y la posibilidad de una construcción delirante. A continuación, se compara la solución de Joyce con la de Van Gogh para sostener el anudamiento. Finalmente se conjetura que fueron dos los recursos de compensación que utilizó el pintor para reparar la falla del nudo: por un lado, sus relaciones imaginarias con Theo y Gauguin y por otro lado, su producción artística, aunque éstos no fueron suficientes para evitar el destino del pintor.(AU)


Assuntos
Humanos , Transtornos Psicóticos/psicologia , Delírio/psicologia , Teoria Psicanalítica , Arte , Pinturas/psicologia
18.
Rev. univ. psicoanál ; 9: 211-228, nov. 2009.
Artigo em Espanhol | LILACS | ID: lil-557624

RESUMO

El presente trabajo tiene como objetivo determinar cuáles fueron los modos de compensación de la psicosis en Van Gogh. Se busca indagar los recursos que posibilitaron al artista remediar provisoriamente, la carencia simbólica. Como fuente biográfica principal se utiliza el intercambio epistolar entre el pintor y su hermano Theo. El análisis que se efectúa es de carácter exploratorio, bajo los aportes de Jaques Lacan. Se procede a examinar la categoría de fenómeno elemental para interrogase sobre la alucinación y la posibilidad de una construcción delirante. A continuación, se compara la solución de Joyce con la de Van Gogh para sostener el anudamiento. Finalmente se conjetura que fueron dos los recursos de compensación que utilizó el pintor para reparar la falla del nudo: por un lado, sus relaciones imaginarias con Theo y Gauguin y por otro lado, su producción artística, aunque éstos no fueron suficientes para evitar el destino del pintor.


Assuntos
Humanos , Delírio/psicologia , Teoria Psicanalítica , Transtornos Psicóticos/psicologia , Arte , Pinturas/psicologia
19.
Mutat Res ; 665(1-2): 14-9, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19427506

RESUMO

RecBCD and RecFOR homologous recombination pathways induced bacterial chromosomal duplication-segregation by sodium selenite (SSe) at sub-inhibitory concentrations. This evidence suggests that SSe induces both, double and single DNA strand damage with a concomitant DNA repair response, however the strong dependence for recombinogenic activity of RecB product suggests that the main DNA repair pathway copes with dsDNA breaks. A role for SSe recombinogenic induction is proposed to explain its effect on DNA instability.


Assuntos
Deleção Cromossômica , Cromossomos Bacterianos/efeitos dos fármacos , Cromossomos Bacterianos/genética , Exodesoxirribonuclease V/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Selenito de Sódio/toxicidade , Proteínas de Bactérias/metabolismo , Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Genes Bacterianos , Recombinação Genética , Salmonella typhimurium/metabolismo
20.
Cir. Esp. (Ed. impr.) ; 85(5): 280-286, mayo 2009. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-59627

RESUMO

Objetivo: Describir los datos enviados al Registro Nacional de Cirugía Gástrica por laparoscopia y analizar el tipo de cirugía, la reconversión, las complicaciones postoperatorias y la mortalidad. Pacientes y método: Desde marzo de 2005 a julio de 2008 han sido remitidos al registro 302 pacientes a través de un cuestionario ubicado en la página web de la Asociación Española de Cirujanos, donde se registraron datos clinicopatológicos, características de la cirugía realizada, reconversión y morbimortalidad. Resultados: Se ha intervenido a 245 pacientes por adenocarcinoma gástrico, 35 por tumores estromales y 22 por otras afecciones. En los adenocarcinomas gástricos se realizó cirugía resectiva en 232 (95%) casos. La localización predominante fue el tercio distal y el tipo de tumor más frecuente, el intestinal. El 34% fueron tumores localmente avanzados. Se realizó una linfadenectomía D2 en 117 casos, D1 en 105 y D0 en 6. Se realizó reconversión en 21 (9%), y entre las causas destacan las dificultades técnicas. Se han descrito complicaciones postoperatorias en 72 (31%) casos, entre las que destacan por su gravedad las fístulas digestivas. Hubo una mortalidad postoperatoria del 6%, y las causas más frecuentes fueron la sepsis por fuga anastomótica y las complicaciones cardiorrespiratorias. La estancia media hospitalaria en los pacientes que no presentaron complicaciones fue de 9,2±3 días. Conclusiones: La gastrectomía laparoscópica en el cáncer gástrico es un procedimiento factible que no está exento de dificultades técnicas. Una considerable tasa de complicaciones postoperatorias pueden llegar a condicionar los beneficios de la cirugía mínimamente invasiva(AU)


Objective: To study the data from the Laparoscopic Gastric Surgery Spanish National Register of laparoscopic Gastric Surgery and to analyse the type of surgery, the conversion to laparotomy, postoperative complications and mortality. Patients and Method: From March 2005 to July 2008, details of 302 laparoscopic gastric surgical interventions were sent to the Association of Spanish Surgeons web-site. Details of surgical technique, reconversion, clinical and pathological data, morbidity and mortality were collected and analysed. Results: A total of 245 patients had gastric adenocarcinoma, 35 of them stromal tumours and 22 other gastric pathologies. In gastric adenocarcinoma patients, resection was performed in 232 cases (95%). The most frequent histology was intestinal, mainly located in the distal third of the stomach, with 34% of the tumours being locally advanced. D2 lymphadenectomy was performed in 117 cases, D1 in 105, and D0 in 6. Reconversion was needed in 21 cases (9%), with technical difficulty being the most frequent cause . Postoperative complications were reported in 72 patients (31%), with anastomotic leak being one of the most significant. Postoperative mortality was 6%, with sepsis due to anastomotic leak and cardiac or respiratory complications the most frequent causes. The mean hospital stay of patients without complications was 9.2±3 days.Conclusions: Laparoscopic gastrectomy for gastric cancer is a feasible but technically demanding procedure. Potential benefits of minimal invasive surgery can be reduced due to a high rate of postoperative complications(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Laparoscopia/estatística & dados numéricos , Neoplasias Gástricas/epidemiologia , Controle de Formulários e Registros/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Inquéritos e Questionários , Indicadores de Morbimortalidade , Excisão de Linfonodo/estatística & dados numéricos , Gastrectomia/estatística & dados numéricos , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Neoplasias Gástricas/cirurgia , Controle de Formulários e Registros/classificação , Prontuários Médicos/estatística & dados numéricos , Neoplasias Gástricas/complicações , Inquéritos e Questionários/classificação , Adenocarcinoma/complicações , Adenocarcinoma/epidemiologia , Tumores do Estroma Gastrointestinal/epidemiologia
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