Frequency of the BCR/ABL rearrangements and associated alterations detected by FISH during monitoring of patients taking imatinib mesylate in isolation

A introdução do mesilato de imatinibe como tratamento da leucemia mielóide crônica tem salvado muitos pacientes, mas o sucesso da terapia tem sido prejudicado pela resistência e possível não destruição do clone maligno. Este artigo descreve a resposta citogenética e padrões citogenéticos anormais envolvendo os genes ABL e BCR detectados por FISH em pacientes em uso exclusivo de imatinibe. Os resultados mostraram que outras alterações envolvendo os genes BCR e ABL não parecem estar relacionadas à resistência à droga, elas ocorrem em baixas freqüências e podem não estar associadas à resposta citogenética ou ao tempo de tratamento. Contudo, a resposta ao imatinibe parece ser individual e imprevisível, independente do tempo e do início do tratamento após o diagnóstico.

The changing pattern of analgesic and anti-inflammatory drug use in cleft lip and palate repair

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Characterization of PLGA microparticles as a drug carrier for 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one. Ultrastructural study of cellular uptake and intracellular distribution

Here we describe the application of microparticles (MPs) for the delivery and release of the drug a benzopsoralen. We also evaluated the intracellular distribution and cellular uptake of the drug by using an encapsulation technique for therapeutic optimization. MPs containing the compound 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one (psoralen A) were prepared by the solvent evaporation technique, and parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process on the drug's photochemistry, zeta potential, external morphology, and < i > in vitro release behavior were evaluated. The intracellular distribution of MPs as well as their uptake by tissues were monitored. Size distribution studies using dynamic ligh scattering and scanning electron microscopy revealed that the MPs are spherical in shape with a diameter of 1.4 mu m. They present low tendency toward aggregation, as confirmed by their zeta potential (+10.6 mV). The loading efficiency obtained was 75%. As a consequence of the extremely low diffusivity of the drug in aqueous medium, the drug release profile of the MPs in saline phosphate buffer (pH 7.4) was much slower than that obtained in the biological environment. Among the population of peritoneal phagocytic cells, only macrophages were able to phagocytose poly-d,l-lactic-co-glycolic acid (PLGA) MP. The use of psoralen A in association with ultraviolet light (360 nm) revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondria condensation, and swelling of both the granular endoplasmatic reticulum and the nuclear membrane. These results indicate that PLGA MP could be a promising delivery system for psoralen in connection with ultraviolet irradiation therapy (PUVA).

Calibration of therapeutic ultrasound equipment

Temporal and spatial acoustic intensity (SATA) of therapeutic ultrasound (US) equipment should be monitored periodically. In order to evaluate the conditions of US equipment in use in the city of Piracicaba-Sao Paulo, Brazil, 31 machines - representing all Brazilian manufacturers - were analysed under continuous and pulsed conditions at a frequency of 1 MHz. Data about temporal and spatial acoustic intensity were collected and the use of equipment was surveyed. Intensities of 0.1, 0.2, 0.5, 0.8, 1.0, 1.5, 2.0, 2.5 and 3.0 Wcm -2, indicated on the equipment panel were analysed using a previously calibrated digital radiation pressure scale, model UPM-DT-1 (Ohmic Instruments Co). The acoustic intensity (I) results were expressed as superior and inferior quartile ranges for transducers with metal surfaces of 9 cm 2 and an effective radiation area (ERA) Of 4 cm 2. The results under continuous conditions were: I 0.1 = -20.0% and -96%. I 0.2 = -3.1% and -83.7%. I 0.5 = -35.0% and -86.5%. I 0.8 = -37.5% and -71.0%. I 2.5 = -49.0% and -69.5%. I 3.0 = -58.1% and -77.6%. For pulsed conditions, intensities were: I 0.1 = -40.0% and -86.2%. I 1.0 = -50.0% and -86.5%. I 1.5 = -62.5% and -82.5%. I 2.0 = -62.5% and -81.6%. I 2.5 = -64.7% and -88.8%. I 3.0 = -87.1% and -94.8%. In reply to the questionnaire drawn up to check the conditions of use of equipment, all users reported the use of hydrosoluble gel as a coupling medium and none had carried out previous calibrations. Most users used intensities in the range of 0.4. to 1.0 Wcm -2 and used machines for 300 to 400 minutes per week. The majority of machines had been bought during the previous seven years and weekly use ranged from less than 100 minutes to 700 minutes (11 hours 40 minutes). Findings confirm previous observations of discrepancy between the intensity indicated on the equipment panel and that emitted by the transducer and highlight the necessity for periodic evaluations of US equipment.

Therapeutic response of benzodiazepine, orphenadrine citrate and occlusal splint association in TMD pain

Loss of function, muscle inflammation, and pain are some of the signs and symptoms of temporomandibular dysfunction (TMD). Pharmacological strategies to minimize the clinical manifestation of these disorders often focus on blocking or inhibiting the pain-causing symptom. Resources such as muscle-relaxants, anxiety-relief drugs, and splint therapy are often used to reduce muscular hyperactivity related to TMD muscle pain. This study compares the effect of a randomly ordered association of occlusal splint therapy (S), nonsteroid anti-inflammatory with a muscle-relaxant drug (orphenadrine citrate) (O), and an anxiety-relief drug (benzodiazepine) (B), to ease painful TMD muscle symptoms. Clinical and anamnestic analyses were recorded in accordance with the Helkimo TMD index and applied before and after treatments. Twenty-one group two Helkimo TMD adult female patients were treated, all of whom were subjected to the three random therapeutic associations proposed: SBO, BOS, and OSB. The same operator applied the three specific associations over a period of 21 days in the proposed sequence, seven days for each therapy. The results show that all the groups presented the best results in terms of relief from pain after the therapeutic association (28.5% showed a decrease and 47.6% showed an absence of symptoms). No significant difference was observed among association therapeutic protocols. Copyright © 2003 by CHROMA, Inc.

Uso do óxido nítrico em pediatria

Objective: To review the literature on inhaled nitric oxide and to describe its main clinical applications in pediatrics. Sources of data: A 10 year literature review with selection of the most important publications on inhaled nitric oxide, using the Medline and Cochrane Systematic Review databases. Summary of the findings: This review was organized as follows: introduction; metabolism and biological effects; clinical applications; dosage, gas administration and weaning; precautions and side-effects. Inhaled nitric oxide use was described in persistent pulmonary hypertension and hypoxia of the newborn, acute respiratory distress syndrome, primary pulmonary hypertension, heart surgery, chronic obstructive pulmonary disease, sickle cell anemia, and bronchospastic disease. Conclusions: Inhaled nitric oxide is a therapeutic approach with wide clinical applications in pediatrics. Its use is safe when administered in pediatric intensive care units under strict monitoring. As a pulmonary vasodilator, nitric oxide has beneficial effects on gas exchange and ventilation. Controlled trials, focusing on early gas administration should be performed under many clinical conditions, especially acute respiratory distress syndrome.

Quantification of sex pheromone from Anocentor nitens by gas chromatography-mass spectrometry-selected ion monitoring

Two highly sensitive and selective methods based on gas chromatography coupled to mass spectrometry (GC-MS) in the selected ion monitoring (SIM) mode have been developed for the quantification of 2,6-dichlorophenol (2,6-DCP), a sex pheromone of the tick females of Anocentor nitens. Standard addition method and calibration curve techniques using 5-bromine-4-hydroxy-3- methoxybenzaldehyde (5-BrV) as internal standard (IS) afforded detection limit of 0.1ngml-1. The calibration curve was linear over the concentration range from 0.5 to 500ngml-1 for 2,6-DCP. Results show that the concentration range of sex pheromone in the extracts samples was 1.08-10.35ngml-1. The methods developed provided reliable procedures to determine amounts of 2,6-DCP present in ticks. © 2003 Elsevier B.V. All rights reserved.

Comparative therapeutic use of Risedronate and Calcarea phosphorica - Allopathy versus homeopathy - In bone repair in castrated rats

Osteoporosis, a disease characterized by progressive bone loss, has been the target of several studies in the past few years. It results in a much higher risk for fractures and might cause slower bone lesion healing. The aim of this work was to study the effects of Risedronate (allopathic medicine) and Calcarea phosphorica 6CH (homeopathic medicine) on the repair of bone lesions in male rats with osteoporosis induced by castration. Eighty-four three-month-old rats were used divided into four groups of twenty-one animals each. Three groups where castrated and one group was submitted to Sham surgery. One month later, cortical lesions were made in all animals' tibiae and, after one day, the different experimental treatments began according to the following groups: CR - castrated/Risedronate (1 mg/kg/day); CCp - castrated/ Calcarea phosphorica 6CH (3 drops/day); CP - castrated/placebo and SP - Sham/placebo. The animals were sacrificed at seven, fourteen and twenty-eight days after the beginning of the treatments and had their tibiae removed. Digital radiographs of the tibiae were taken and analyzed in order to evaluate the optical density of the defect area. Then, they were decalcified and processed for histological and histomorphometrical analysis. The data were submitted to ANOVA, and to the Tukey and Dunnett tests (5%). The allopathic and homeopathic treatments led to different bone formation as regards remodeling and maturation aspects. Further research is necessary to access the resistance and quality of the newly formed bone.

Therapeutic option for children with esophageal caustic stenosis

Caustic ingestion is a leading cause of esophageal stenosis in children. Herein we report four cases using mitomycin C (MMC), a drug that inhibits cell division, protein synthesis and fibroblast proliferation and has been used as an adjuvant therapy for caustic esophageal stenosis that is recalcitrant to conventional dilation techniques. A retrospective chart review was performed on four pediatric patients with severe, recurrent esophageal stricture after caustic ingestion. The patients had required six to 20 esophageal dilations over a 4-16-month period before MMC application. MMC was applied after an endoscopic dilation on saturated pledgets at a dose of 0.1 mg/mL for 2 min in the area where the strictures had been lyzed. From the four children treated with MMC, two have been asymptomatic for 16 and 20 months and two still require esophageal dilation, however, at longer intervals. All patients have shown satisfactory weight gain with food intake exclusively per oral. Although further studies are required, there is strong evidence that MMC is a safe and effective adjuvant therapy in the treatment of esophageal caustic stenosis. © 2008 The Authors.

Adverse drug reaction as cause of hospital admission of elderly people: a pilot study

The objective of this study was to estimate the prevalence of adverse drug reactions (ADR) related to hospital admission of elderly people, identifying the use of potentially inappropriate medication (PIM), the ADR and the risk factors associated with the hospitalization. A cross-sectional study was conducted in a private hospital of São Paulo State, Brazil. All patients aged ≥ 60 years, admitted in the general practice ward in May 2006 were interviewed about the drugs used and the symptoms/complaints that resulted in hospitalization. More than a half (54.5 %) of elderly hospitalizations were related with ADR. The therapeutic classes involved with ADR were: cardiovascular (37.7 %), central nervous (34.6 %) and respiratory (5.7 %). The ADR observed were disorders in circulatory (28.4 %), digestive (20.0 %) and respiratory (18.9 %) tracts. 27 elderly had made PIM and in 20 of them this was the cause of hospitalization. Polypharmacy was an ADR risk factor (p = 0.021).These data allows the healthcare professionals upgrade, qualifying them in pharmcovigilance.

Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drugresistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options. © 2013 SGM.

Orbifloxacin: A Review of Properties, Its Antibacterial Activities, Pharmacokinetic/Pharmacodynamic Characteristics, Therapeutic Use, and Analytical Methods

Orbifloxacin is a third generation of fluoroquinolone that exhibits increased antibacterial activity against the Enterobacteriaceae, gram-negative and gram-positive bacteria, anaerobes, and mycobacteria. This drug was synthesized in 1987 and developed as a veterinary chemotherapeutic to use for livestock and domestic pets. Orbifloxacin is labeled for the treatment of skin, soft tissue, and urinary tract infections in dogs, and skin and soft tissue infections in cats, but in some countries, orbifloxacin has been given for the treatment of gastrointestinal and respiratory infections in cattle and swine and other animals. The in vitro activity and clinical efficacy of orbifloxacin against naturally occurring bacterial infections of the skin, ear, soft tissue, udder, and gastrointestinal and respiratory systems in different animals have been evaluated and good responses have been found. The minimum inhibitory concentration of orbifloxacin has been determined in various different pathogens and the results found in the literature are shown in this work. The pharmacokinetics of orbifloxacin has been evaluated by different routes of administration in goats, horses, pigs, rabbits, dogs, cats, camels, cattle, sheep, and fish. Orbifloxacin exhibits excellent pharmacokinetic parameters that suggest that this drug may have good clinical effects on various bacterial infections in these species. All methods described in the scientific literature for determination of orbifloxacin in different matrices were collected and discussed. © 2013 Copyright Taylor and Francis Group, LLC.

Internações hospitalares por reações adversas a medicamentos (RAM) em um hospital de ensino

Pós-graduação em Ciências Farmacêuticas - FCFAR

Determinação das concentrações plasmáticas de amitriptilina por cromatografia líquida de alta eficiência em pacientes com hanseníase e estados reacionais

A hanseníase é uma doença infecciosa crônica, causada pelo Mycobacterium leprae, que afeta preferencialmente nervos periféricos e pele. O acometimento nervoso é responsável por deformidades e sintomatologia dolorosa, com consequente diminuição da qualidade de vida dos pacientes. A amitriptilina vem sendo utilizada como droga de escolha no alívio da dor neuropática nesses indivíduos. Entretanto, considerando a estreita faixa terapêutica e a importante variabilidade interindividual desse fármaco, faz-se necessário a monitorização de suas concentrações plasmáticas a fim de otimizar os esquemas terapêuticos. Neste sentido, o objetivo deste estudo foi validar metodologia analítica por Cromatografia Líquida de Alta Eficiência, determinar as concentrações plasmáticas de amitripitilina, bem como comparar as concentrações plasmáticas de amitriptilina com a presença de poliquimioterapia e o tipo de episódio reacional nos pacientes atendidos no Ambulatório do Núcleo de Medicina Tropical, que utilizaram doses de 25 e 50 mg/dia. A técnica validada demonstrou resultados adequados e perfeitamente aplicáveis à metodologia desejada. Dentre os pacientes participantes do estudo, 12 (57%) foram do sexo masculino e 9 (43%) feminino. Em relação ao período de ocorrência do episódio reacional 8 pacientes (38%) estavam fazendo uso da poliquimioterapia e 13 pacientes (62%) após o término do tratamento. Dez pacientes (47%) participantes do estudo apresentaram episódio reacional tipo I e 11 (53%) do tipo II. A concentração plasmática média de amitriptilina na dose 25mg/dia foi de 318 144 ng/mL e na dose de 50 mg/dia foi de 361,08 182. O coeficiente de variação foi de 53, 16 e 50,5 respectivamente.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.