Estudos de medicamentos biosimilares

In Brazil, the registration of new drugs is carried out only when the regulatory agency (Anvisa, acronym in Portuguese) is fully satisfied with the evidence of their quality, efficacy and safety, presented by a pharmaceutical industry that strive for this registration. With the patent expiration, pharmaceutical companies are attracted to produce biological medicines called biosimilar or biogenerics or simply generics, whose approval may result in reduced treatment costs. But it is necessary that the biosimilar be, at least, equally efective and safe and without contaminants in relation to the original. Recent consensus guidelines aim to establish criteria for efcacy and safety of these medicines. Preclinical studies in vitro and in vivo, the origin of raw materials and clinical studies phase I, II and III are recommended for biosimilar medicine registration in the international market. Low molecular weight heparins are found in this situation. In this review we specifcally addressed this type of medicine, which could serve as a benchmark for other biosimilar medicines.

Comparação entre hipertensão autoreferida e pressão arterial casual e presença de fatores de risco em funcionários da saúde Bauru e Jaú

Model: Prevalence study. Objectives: To evaluate the presence of self-reported hypertension to compare with blood pressure measurements. Besides, this work investigated health information level of workers and if the job position has any influence on blood pressure (BP). Methods: This study evaluated 349 health workers (44±10 years old) from Bauru and Jau cities, who answered some questions about history of health condition, use of medicines, past surgeries as well as social, scholar and physical conditions and had their blood pressure measured. Each subject selfreported as normotensive or hypertensive. Values of systolic ≥ 140 mmHg and/or diastolic PA ≥ 90 mmHg were considered elevated. Among the health workers evaluated, 198 were submitted to anthropometric and biochemical evaluations. Values are presented as means ± SD and frequency of distribution. It was used T-student test (p<0.05). Results: From all workers evaluated only 16% self-reported as hypertensive, which 56% presented high BP, however 91% used to take antihypertensive medicines. Among the 84% who self-reported as normotensive, 24% presented high BP and 8% used to take medicines. Although most of the employees of each section self-reported as normotensive, more than a half presented high BP and which was more common in the health's section (76.3%). Conclusion: These results suggest that besides the majority of the employees self-reported as normotensive, an elevated number of health workers presented high blood pressure and used to take medicines inappropriately, which indicates that they did not have enough knowledge about their health. Furthermore, it was observed that Health Section presented the higher blood pressure values.

Development and validation of a microbiological agar assay for determination of orbifloxacin in pharmaceutical preparations

Orbifloxacin is a fluoroquinolone with broad-spectrum antimicrobial activity, and belongs to the third generation of quinolones. Regarding the quality control of medicines, a validated microbiological assay for determination of orbifloxacin in pharmaceutical formulations has not as yet been reported. For this purpose, this paper reports the development and validation of a simple, sensitive, accurate and reproducible agar diffusion method to quantify orbifloxacin in tablet formulations. The assay is based on the inhibitory effect of orbifloxacin upon the strain of Staphylococcus aureus ATCC 25923 used as test microorganism. The results were treated statistically by analysis of variance and were found to be linear (r = 0.9992) in the selected range of 16.0-64.0 μg/mL, precise with relative standard deviation (RSD) of repeatability intraday = 2.88%, intermediate precision RSD = 3.33%, and accurate (100.31%). The results demonstrated the validity of the proposed bioassay, which allows reliable orbifloxacin quantitation in pharmaceutical samples and therefore can be used as a useful alternative methodology for the routine quality control of this medicine. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Evaluation of electrical conductivity, pH and refractive index as physico-chemical parameters for quality control of Aveloz homeopathic solutions

Euphorbia tirucalli Lineu (Aveloz) belongs to the family Euphorbiaceae and is used in the treatment of cancer and warts. Some studies have reported that phorbol esters are the active principles responsible for the antitumor activity of Aveloz. The production of these molecules occurs in greater quantity in May, during the morning. This study aimed to evaluate whether the physico-chemical parameters of Aveloz homeopathic aqueous solutions such as pH, electrical conductivity and refractive index change due to storage time. Such parameters were measured regularly for 180 days. All solutions were prepared according to the method of grinding with lactose and subsequent dissolution in aqueous medium, as described in the Brazilian Homeopathic Pharmacopoeia, using as starting point the Aveloz latex collected in May. Homeopathic aqueous solutions containing only lactose were also prepared and evaluated as a control group. The potencies that were analyzed for electrical conductivity, pH and refractive index were: 4cH, 7cH, 9cH, 12cH, 14cH, 15cH, 29cH, 30cH. As a result, we found out that there was only statistical difference (p=0.035) in electrical conductivity between the homeopathic solutions containing Aveloz and the homeopathic solutions without Aveloz, when 15cH potency was compared. We also observed that the electrical conductivity increased with the aging of the solutions but is not directly related to the pH or the refractive index of the solutions, indicating that the aging process may alter the electrical conductivity of the homeopathic medicines. The presence of gas inside the glass that stores these solutions may affect the electrical conductivity measurements. Finally, no statistically significant difference was observed (p> 0.05) in the pH and refractive index.

Polimorfismo na produção de medicamentos

Polymorphism can cause quality deviations during the production of medicines and can influence their effectiveness. Therefore, an understanding of this phenomenon and its implications opens a wide field of possibilities to be explored in the pharmaceutical field, including the emergence of new paradigms and tools for the quality assurance of medicines. This paper presents an introduction to basic aspects of the polymorphism phenomenon and its implications for the production and control of medicines, with emphasis on drug polymorphs.

Development and validation of a successful microbiological agar assay for determination of ceftriaxone sodium in powder for injectable solution

Ceftriaxone sodium is a cephalosporin with broad-spectrum antimicrobial activity and belongs to the third generation of cephalosporins. Regarding the quality control of medicines, a validated microbiological assay for the determination of ceftriaxone sodium in powder for injectable solution has not been reported yet. This paper reports the development and validation of a simple, accurate and reproducible agar diffusion method to quantify ceftriaxone sodium in powder for injectable solution. The assay is based on the inhibitory effect of ceftriaxone sodium on the strain of Bacillus subtilis ATCC 9371 IAL 1027 used as test microorganism. The results were treated statistically by analysis of variance and were found to be linear (r = 0.999) in the selected range of 15.0-60.0 μg/mL, precise with a relative standard deviation (RSD) of repeatability intraday = 1.40%, accurate (100.46%) and robust with a RSD lower than 1.28%. The results demonstrated the validity of the proposed bioassay, which allows reliable ceftriaxone sodium quantitation in pharmaceutical samples and therefore can be used as a useful alternative methodology for the routine quality control of this medicine. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

Tachycardia-induced cardiomyopathy

Tachycardia-induced cardiomyopathy (TIC) is an important cause of heart failure as it is potentially reversible after ventricular rate control. A 66-year-old hypertensive woman presented with a 15-day history of tachycardia, dyspnoea and oedema. ECG revealed atrial fibrillation with ventricular frequency of 130 beats per minute (bpm). Echocardiogram showed dilated left ventricle (LV) with 0.39 ejection fraction. Angiography revealed non-obstructed coronary arteries. Heart rate and cardiac failure were controlled with amiodarone, digoxine, captopril, metoprolol and furosemide. During follow-up, despite drug dose optimisation, the patient kept complaining of tachycardia and dyspnoea with a ventricular rate between 108 and 120 bpm. Medical staff suspected she was not taking her medicines properly. Two months later, the patient was asymptomatic and had converted to sinus rhythm (heart rate of 76 bpm). Echocardiogram showed normal LV size and function. Patient 's diagnosis was TIC. Although rare, TIC should be considered in all cases of systolic dysfunction associated with tachyarrhythmia. Copyright 2012 BMJ Publishing Group. All rights reserved.

Concentração letal LC50 do extrato aquoso de folhas de terminalia catappa em guaru, phalloceros caudimaculatus

This trial was conducted in order to determine the 50% lethal concentration (LC (I) 50-96h) of the aqueous extract of dried leaves of Terminalia catappa, a plant with antifungal, antibacterial and antiparasitic activity. Due to the increasing use of herbal medicines in aquaculture, its use is an option for controlling diseases in fish. Toxicity tests are important before recommending any treatment, since some products have therapeutic concentration close to lethal. To conduct the study used 135 fish species Guarus (Phalloceros caudimaculatus), exposed to increasing concentrations of: 0.0, 50.0, 100.0, 150.0, 200.0, 250.0, 300.0 mL of stock solution per liter of water. The results were calculated by the method Trimmed Spearman Karbo, demonstrating that the 50% lethal concentration (LC (I) 50-96h) estimated was 208.52 mL / L, with lower limit of 187.79 mL / L and higher 231.54 mL / L. Observed changes in behavior of the test organisms at concentrations above 250 mL / L decrease in the levels of dissolved oxygen and pH. Concentrations below 250 mL /L result in mortality rate near zero, so the aqueous extract shown low toxicity.

Exportação de nutrientes em plantas de jambu, sob diferentes adubações

The jambu is a broad vegetable consumption in Northern Brazil, especially in Pará, known by the jambu and other common names is native to the Amazon region has been used and cultivated for culinary and also recently in natural medicines by their chemical properties, attributed to the spilanthol compound. Knowing the amount of nutrient uptake in plants, especially at the taken, it is important to evaluate the removal of nutrients necessary for economic fertilizer recommendations. So the goal of this project was to determine the accumulation of nutrients in plants of jambu (leaf and inflorescence) under different fertilizations. The experiment was conducted at São Manuel Experimental Farm UNESP. The statistical was arranged in the randomized block design, in a 2 x 6 factorial scheme, two sources of fertilizers (organic and mineral) and six doses of nitrogen, with four replications. We evaluated the macronutrients of accumulation N, P, K, Ca, Mg, S and micronutrients of accumulation B, Cu, Fe and Zn in leaves and inflorescence. The plants responded more jambu nutrients of translocation phosphorus (P), magnesium (Mg), sulfhur (S), boron (B), copper (Cu) and iron (Fe) in the inflorescences and phosphorus (P), calcium (Ca), manganese (Mg), sulfur (S), boron (B), copper (Cu) and iron (Fe) in leaves to organic fertilization demonstrating the effectiveness of using this source of fertilizer nutrients indicating that this was a defining characteristic in response to the accumulation of nutrients in the leaves and inflorescences jambu. Plants jambu are more responsive to fertilizer for the mineral of translocation nitrogen (N) and manganese (Mn) for both the sheet and for the inflorescences of plants jambu.

Gastroprotective mechanisms of the chloroform and ethyl acetate phases of Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae)

Flavonoid-rich Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae) is a native plant of South America. This study evaluates the gastroprotective activity and possible mechanisms for both the chloroform (CHCl3P) and ethyl acetate phases (AcOEtP) obtained from aerial parts of the plant. The activity was investigated using acute models of gastric ulcer. Gastric secretion biochemical parameters were determined after pylorus ligature. The participation of cytoprotective factors such as mucus, nitric oxide (NO), sulfhydryl (SH) groups, prostaglandin E2 (PGE 2), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), reduction of lipid peroxidation (malondialdehyde level), and polymorphonuclear infiltration (myeloperoxidase activity), was also investigated. CHCl3P (125, 250, and 500 mg/kg) and AcOEtP (62.5, 125, and 250 mg/kg) showed significant gastroprotective activity, reducing the ulcerative index by 75, 83, 88 % and 66, 66, 81 % for ethanol; 67, 67, 56 % and 56, 53, 58 % for a non-steroidal anti-inflammatory drug (NSAID); and 74, 58, 59 % and 64, 65, 61 % for stress-induced gastric ulcer, respectively. CHCl3P (125 mg/kg) and AcOEtP (62.5 mg/kg) significantly reduced the ulcerative area by 78 and 83 %, respectively, for the ischemia-reperfusion model. They also did not alter the biochemical parameters of gastric secretion, the GSH level or the activities of SOD, GPx or GR. They increased the quantity of gastric mucus, not dependent on NO, yet dependent on SH groups, and maintained PGE2 levels. The P. clematidea phases demonstrated gastroprotective activity related to cytoprotective factors. © 2012 The Japanese Society of Pharmacognosy and Springer.

Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions

The malaria treatment recommended by the World Health Organization involves medicines derived from artemisinin, an active compound extracted from the plant Artemisia annua, and some of its derivatives, such as artesunate. Considering the lack of data regarding the genotoxic effects of these compounds in human cells, the objective of this study was to evaluate the cytotoxicity and genotoxicity, and expressions of the CASP3 and SOD1 genes in a cultured human hepatocellular liver carcinoma cell line (HepG2 cells) treated with artemisinin and artesunate. We tested concentrations of 2.5, 5, 7.5, 10, and 20 μg/mL of both substances with a resazurin cytotoxicity assay, and the concentrations used in the genotoxicity experiments (2.5, 5, and 10 μg/mL) and gene expression analysis (5 mg/mL) were determined. The results of the comet assay in cells treated with artemisinin and artesunate showed a significant dosedependent increase (P < 0.001) in the number of cells with DNA damage at all concentrations tested. However, the gene expression analysis revealed no significant change in expression of CASP3 or SOD1. Our data showed that although artemisinin and artesunate exhibited genotoxic effects in cultured HepG2 cells, they did not significantly alter expression of the CASP3 and SOD1 genes at the doses tested. ©FUNPEC-RP.

Avaliação da capacidade antioxidante de extratos vegetais de plantas brasileiras e sua contribuição ao estudo de inibição da enzima mieloperoxidase

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Diabetes mellitus tipo 2 e esquema terapêutico: impacto da prática de atividades físicas sobre o custo do tratamento ambulatorial em Unidade Básica de Saúde da cidade de Bauru -SP

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influência da prática de atividades físicas sobre os gastos com saúde de pacientes vinculados a uma cooperativa médica

Pós-graduação em Ciências da Motricidade - IBRC

Efeitos de ultradiluições de drogas carcinogênicas iniciadoras e da dexametasona na carcinogênese hepática de ratos

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC