Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Drug resistance of M. Tuberculosis isolated from patients with HIV infection seen at an AIDS Reference Center in São Paulo, Brazil

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

Etiological drug treatment of human infection by Trypanosoma cruzi

Forty-nine American Trypanosomiasis (Chagas' disease) patients, with xenodiagnosis proven parasitemia were treated by the authors. Forty-one of these patients were given benznidazole, at dosages ranging from 5mg/kg/day to 8mg/kg/day, during a pre-established period of 60 days. In this group, 17 patients had an undetermined form of the disease, whereas 22 had cardiologic disease and 4 had digestive disease (two patients had a mixed form of the disease). Side effects were frequent, and led to the discontinuation of treatment in 17 patients. The follow-up period ranged from 1 to 20 years (mean follow-up period of 6 yrs. 7 mo). 26 (63.4%) of the patients became parasitemia-negative. The other eight patients were treated with nifurtimox, during 120 days, following a variable dose regime of 5mg/kg/day (initial dose) to 17 mg/kg/day (final dose). Six of them had severe side effects, and only one patient remained parasitemia-negative throughout the observation period (ranging from 1 to 18 years). Benznidazole proved to be better tolerated and more effective in the management of parasitemia when compared to nifurtimox, although more effective and less toxic drugs are still desirable.

Talk on water ecological economics and participatory watershed governance

Dissertação apresentada para obtenção do Grau de Doutor em Ambiente pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Evolution of Drug Resistance: Insight on TEM β-Lactamases Structure and Activity and β-Lactam Antibiotics

Since the discovery of the first penicillin bacterial resistance to β-lactam antibiotics has spread and evolved promoting new resistances to pathogens. The most common mechanism of resistance is the production of β-lactamases that have spread thorough nature and evolve to complex phenotypes like CMT type enzymes. New antibiotics have been introduced in clinical practice, and therefore it becomes necessary a concise summary about their molecular targets, specific use and other properties. β-lactamases are still a major medical concern and they have been extensively studied and described in the scientific literature. Several authors agree that Glu166 should be the general base and Ser70 should perform the nucleophilic attack to the carbon of the carbonyl group of the β-lactam ring. Nevertheless there still is controversy on their catalytic mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due to their tolerance to mutations. These mutations lead to an increasing need of novel, stronger and more specific and stable antibiotics. The present review summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT TEM β-lactamases properties and up to date diagrams of the TEM variants with defined phenotype. The activity and structural characteristics of several available TEMs in the NCBI-PDB are presented, as well as the relation of the various mutated residues and their specific properties and some previously proposed catalytic mechanisms.

The role of molecular imaging in modern drug development

Drug development represents a highly complex, inefficient and costly process. Over the past decade, the widespread use of nuclear imaging, owing to its functional and molecular nature, has proven to be a determinant in improving the efficiency in selecting the candidate drugs that should either be abandoned or moved forward into clinical trials. This helps not only with the development of safer and effective drugs but also with the shortening of time-to-market. The modern concept and future trends concerning molecular imaging will assumedly be hybrid or multimodality imaging, including combinations between high sensitivity and functional (molecular) modalities with high spatial resolution and morphological techniques.

Development of cyclodextrin-hydrogel polymeric systems in scCO2 for drug delivery

Thesis for the Degree of Master of Science in Bioorganic Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Development of electrospun Ion jelly fibers® for drug delivery

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Development of paper-based color test-strip for drug detection in aquatic environment: Application to oxytetracycline

The wide use of antibiotics in aquaculture has led to the emergence of resistant microbial species. It should be avoided/minimized by controlling the amount of drug employed in fish farming. For this purpose, the present work proposes test-strip papers aiming at the detection/semi-quantitative determination of organic drugs by visual comparison of color changes, in a similar analytical procedure to that of pH monitoring by universal pH paper. This is done by establishing suitable chemical changes upon cellulose, attributing the paper the ability to react with the organic drug and to produce a color change. Quantitative data is also enabled by taking a picture and applying a suitable mathematical treatment to the color coordinates given by the HSL system used by windows. As proof of concept, this approach was applied to oxytetracycline (OXY), one of the antibiotics frequently used in aquaculture. A bottom-up modification of paper was established, starting by the reaction of the glucose moieties on the paper with 3-triethoxysilylpropylamine (APTES). The so-formed amine layer allowed binding to a metal ion by coordination chemistry, while the metal ion reacted after with the drug to produce a colored compound. The most suitable metals to carry out such modification were selected by bulk studies, and the several stages of the paper modification were optimized to produce an intense color change against the concentration of the drug. The paper strips were applied to the analysis of spiked environmental water, allowing a quantitative determination for OXY concentrations as low as 30 ng/mL. In general, this work provided a simple, method to screen and discriminate tetracycline drugs, in aquaculture, being a promising tool for local, quick and cheap monitoring of drugs.

Depositions of rulers in the later middle ages: on the theory of th "useless ruler" and its practical utilization

pp. 157-168

Drug trials for treatment of human angiostrongyliasis

Abdominal and cerebral angiostrongyliasis are two important infections produced by metastrongylid worms, the former occurring in Central and South America and the later in Asia and Pacific Islands. Drug treatment is a challenge since the worms and its evolving larvae live or migrate inside vessels and efficient killing of the parasites may produce more severe lesions. Larvicidal effect of certain drugs appears to be more easily accomplished but this outcome is not useful in abdominal angiostrongyliasis since clinical manifestations appear to result from sexual maturation of the worms. We review the drug trials in murine experimental models and conclude that most of them could not be considered good candidates for treatment of human infection, except for PF1022A, pyrantel and flubendazole.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Evaluation of the in vitro activity of six antimicrobial agents against Neisseria gonorrhoeae

Use of antimicrobials for the treatment of gonorrhea started in 1930 with the utilization of sulfonamides. With the years other drugs were used for its treatment such as penicillin, tetracycline, spectinomycin, and others. Although highly specific in the beginning, these drugs, with time did not show anymore the expected therapeutic results because of aspects of chromosomal and plasmid-mediated resistance. The purpose of this study was to evaluate the susceptibility of Neisseria gonorrhoeae strains to six drugs used for its treatment (penicillin, tetracycline, cefoxitin, thiamphenicol, spectinomycin and ofloxacin) by the determination of minimal inhibitory concentrations of these drugs. We concluded that drugs, such as cefoxitin, thiamphenicol and spectinomycin still are excellent pharmacological agents for the treatment of gonorrhea. Penicillin, although still efficient, needs more attention regarding its use, as well as ofloxacin, because of the emergence of resistant strains. Tetracycline and its derivatives should be strongly contraindicated for the treatment of gonorrhea.

Utilization of Quality Tools: does sector and size matter?

This research focuses on the influence of company sector and size on the level of utilization of Basic and Advanced Quality Tools. The paper starts with a literature review and then presents the methodology used for the survey. Based on the responses from 202 managers of Portuguese ISO 9001:2008 Quality Management System certified organizations, statistical tests were performed. Results show, with 95% confidence level, that industry and services have a similar proportion of use of Basic and Advanced Quality Tools. Concerning size, bigger companies show a higher trend to use Advanced Quality Tools than smaller ones. For Basic Quality Tools, there was no statistical significant difference at a 95% confidence level for different company sizes. The three basic Quality tools with higher utilization were Check sheets, Flow charts and Histograms (for Services) or Control Charts/ (for Industry), however 22% of the surveyed organizations reported not using Basic Quality Tools, which highlights a major improvement opportunity for these companies. Additional studies addressing motivations, benefits and barriers for Quality Tools application should be undertaken for further validation and understanding of these results.