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

Extended-spectrum β-lactamases (ESBLs) prevalence was studied in the north of Portugal, among 193 clinical isolates belonging to citizens in a district in the boundaries between this country and Spain from a total of 7529 clinical strains. In the present study we recovered some members of Enterobacteriaceae family, producing ESBL enzymes, including Escherichia coli (67.9%), Klebsiella pneumoniae (30.6%), Klebsiella oxytoca (0.5%), Enterobacter aerogenes (0.5%), and Citrobacter freundii (0.5%). β-lactamases genes blaTEM, blaSHV, and blaCTX-M were screened by polymerase chain reaction (PCR) and sequencing approaches. TEM enzymes were among the most prevalent types (40.9%) followed by CTX-M (37.3%) and SHV (23.3%). Among our sample of 193 ESBL-producing strains 99.0% were resistant to the fourth-generation cephalosporin cefepime. Of the 193 isolates 81.3% presented transferable plasmids harboring genes. Clonal studies were performed by PCR for the enterobacterial repetitive intragenic consensus (ERIC) sequences. This study reports a high diversity of genetic patterns. Ten clusters were found for E. coli isolates and five clusters for K. pneumoniae strains by means of ERIC analysis. In conclusion, in this country, the most prevalent type is still the TEM-type, but CTX-M is growing rapidly.

Radioactivity studies in Porto urban area: gamma radiation of Paranhos sector

A set of radiation measurements were carried out in several public and private institutions. These were selected with basis on the people affluence and passage to these sites. These measurements were registration formed either indoor, outdoor or underground and were compiled in three Case Studies. Radiation doses measurements were also made, surface and underground locations, and compiled in other two Case Studies. There were sampled, at the same time, humidity, temperature, atmospheric pressure and relevant construction materials at sampling locations. They were collected and registration formed to analyse if there is any relation or contribution for the measured value in each specific place. Geostatistical models were used to elaborate maps of the results both for radiation values and for doses. Preliminary relations were established among the measured parameters.

Cardiac beta-receptors in experimental Chagas' disease

Experimental Chagas' disease (45 to 90 days post-infection) showed serious cardiac alterations in the contractility and in the pharmacological response to beta adrenergic receptors in normal and T. cruzi infected mice (post-acute phase). Chagasic infection did not change the beta receptors density (78.591 ± 3.125 fmol/mg protein and 73.647 ± 2.194 fmol/mg protein for controls) but their affinity was significantly diminished (Kd = 7.299 ± 0.426 nM and Kd = 3.759 ± 0.212 nM for the control) p < 0.001. This results demonstrate that the alterations in pharmacological response previously reported in chagasic myocardium are related to a significantly less beta cardiac receptor affinity. During this experimental period serious cardiac cell alterations take place and functional consequences will be detected in the chronic phase.

Influence of temperature on development of Schistosoma mansoni female cercariae in Biomphalaria glabrata

In these experiments the ratio of male to female S. mansoni larvae in D. glabrata from Belo Horizonte and Ribeirão das Neves Minas Gerais, Brazil, either reared in laboratoty or collected in the field, varied from 1:1 to 1:1.3 or 1.4:1. Cercariae of LE strain of Schistosoma mansoni, shed by 39 snails maintained at 25±0.5ºC were used to infect mice on a weekly basis. Subsequent perfusion resulted in 76.6% male and 23.4% female worms. The cercariac produced by 32 infected snails maintained at 27+0.5°C were inoculated into mice and produced 43.4% male and 56.6% female worms (p<0.05). Cercariae eliminated by snails collected in Barreiro and Ressaca, Belo Horizonte, during hot months, produced 45.7 to 47.7% male and 52.3 to 54.3% female worms. A lower number of cercariae shed by snails collected in Gorduras, Belo Horizonte, at 20+3.0°C, produced 51.6% male and 48.4% female worms. Thus, in this region the infection of vertebrate hosts with S. mansoni cercariae would be more severe in the summer due to the higher level of parasites and the number of eggs.

The effect of temperature on mobility of Angiostrongylus costaricensis third stage larvae

Third stage larvae (L3) from Angiostrongylus costaricensis were incubated in water at room temperature and at 5 ° C and their mobility was assessed daily for 17 days. Viability was associated with the mobility and position of the L3, and it was confirmed by inoculation per os in albino mice. The number of actively moving L3 sharply decreased within 3 to 4 days, but there were some infective L3 at end of observation. A mathematical model estimated 80 days as the time required to reduce the probability of infective larvae to zero. This data does not support the proposition of refrigerating vegetables and raw food as an isolated procedure for prophylaxis of human abdominal angiostrongylosis infection.

Influence of Apolipoprotein E Plasma Levels and Tobacco Smoking on the Induction of Neutralising Antibodies to Interferon-Beta

Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a one-standard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

Fractional State Space Analysis of Temperature Time Series

Atmospheric temperatures characterize Earth as a slow dynamics spatiotemporal system, revealing long-memory and complex behavior. Temperature time series of 54 worldwide geographic locations are considered as representative of the Earth weather dynamics. These data are then interpreted as the time evolution of a set of state space variables describing a complex system. The data are analyzed by means of multidimensional scaling (MDS), and the fractional state space portrait (fSSP). A centennial perspective covering the period from 1910 to 2012 allows MDS to identify similarities among different Earth’s locations. The multivariate mutual information is proposed to determine the “optimal” order of the time derivative for the fSSP representation. The fSSP emerges as a valuable alternative for visualizing system dynamics.

Extended-spectrum beta-lactamases among Enterobacteriaceae isolated in a public hospital in Brazil

Extended-spectrum β-lactamases (ESBL) in enterobacteria are recognized worldwide as a great hospital problem. In this study, 127 ESBL-producing Enterobacteriaceae isolated in one year from inpatients and outpatients at a public teaching hospital at São Paulo, Brazil, were submitted to analysis by PCR with specific primers for blaSHV, blaTEM and blaCTX-M genes. From the 127 isolates, 96 (75.6%) Klebsiella pneumoniae, 12 (9.3%) Escherichia coli, 8 (6.2%) Morganella morganii, 3 (2.3%) Proteus mirabilis, 2 (1.6%) Klebsiella oxytoca, 2 (1.6%) Providencia rettgeri, 2 (1.6%) Providencia stuartti, 1 (0.8%) Enterobacter aerogenes and 1 (0.8%) Enterobacter cloacae were identified as ESBL producers. BlaSHV, blaTEM and blaCTX-M were detected in 63%, 17.3% and 33.9% strains, respectively. Pulsed field gel eletrophoresis genotyping of K. pneumoniae revealed four main molecular patterns and 29 unrelated profiles. PCR results showed a high variety of ESBL groups among strains, in nine different species. The results suggest the spread of resistance genes among genetically different strains of ESBL-producing K. pneumoniae in some hospital wards, and also that some strongly related strains were identified in different hospital wards, suggesting clonal spread in the institutional environment.

Sensibilidade das enterobacteriáceas produtoras de beta-lactamases de espectro alargado à fosfomicina

Introdução: A emergência de enterobacteriáceas produtoras de beta-lactamases de espectro alargado (ESBL) nos últimos anos representa um problema de saúde pública, escasseando alternativas eficazes para o seu tratamento. Vários trabalhos internacionais têm demonstrado uma sensibilidade in vitro muito elevada destas bactérias à fosfomicina, havendo alguns que testaram a eficácia clínica do tratamento de cistites agudas não complicadas no subgrupo das Escherichia coli com resultados promissores. No Hospital Prof. Dr. Fernando Fonseca EPE (HFF) tem havido um aumento anual progressivo do isolamento destes patogéneos. Os autores pretenderam testar a sensibilidade das enterobacteriáceas produtoras de ESBL à fosfomicina no HFF e averiguar o eventual potencial terapêutico. Material e métodos: Estudo prospectivo, durante 6 meses, no qual foi testada a sensibilidade à fosfomicina das enterobacteriáceas produtoras de ESBL isoladas. Foi utilizado o equipamento VITEK 2® para identificação das estirpes. A susceptibilidade à fosfomicina foi determinada através do método de difusão de disco (Oxoid®). O tratamento estatístico foi realizado através do programa Microsoft Excel®. Resultados: Foram identificadas 150 enterobacteriáceas ESBL, das quais 52% corresponderam a Klebsiella pneumoniae e 44% a Escherichia coli. Cerca de 88% das Escherichia coli e 68% das Klebsiella pneumoniae apresentaram sensibilidade à fosfomicina. Conclusões: De acordo com os dados obtidos a nível internacional e no nosso hospital, os autores recomendam a utilização da fosfomicina para tratamento de cistites agudas não complicadas provocadas por Escherichia coli produtoras de ESBL, sugerindo, concomitantemente, a realização de trabalhos futuros de eficácia clínica para consubstanciar esta prática e recomendação.

Spatial and temporal analysis of recent drought using vegetation temperature condition index: case of Somali regional state of Ethiopia

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Spatial-temporal analyses of climate elements, vegetation characteristics and sea surface temperature anomaly. A Case study in Gojam, Ethiopia

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

INTERFERON BETA-1A TREATMENT IN HTLV-1-ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS: A CASE REPORT

Here a young patient (< 21 years of age) with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and laboratory tests confirmed the presence of antibodies to HTLV-1 in the cerebrospinal fluid (CSF). Mumps, cytomegalovirus, Epstein-Barr virus, schistosomiasis, herpes virus 1 and 2, rubella, measles, varicella-zoster toxoplasmosis, hepatitis, HIV, and syphilis were excluded by serology. The patient was diagnosed with neurogenic bladder and presented with nocturia, urinary urgency, paresthesia of the lower left limb, a marked reduction of muscle strength in the lower limbs, and a slight reduction in upper limb strength. During the fourth week of treatment with interferon beta-1a, urinary urgency and paresthesia disappeared and clinical motor skills improved.

Evaluation of thermometers for ear temperature measurement at the wards in a university hospital

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Incorporation of either molybdenum or tungsten into formate dehydrogenase from Desulfovibrio alaskensis NCIMB 13491; EPR assignment of the proximal iron-sulfur cluster to the pterin cofactor in formate dehydrogenases from sulfate-reducing bacteria

J Biol Inorg Chem (2004) 9: 145–151 DOI 10.1007/s00775-003-0506-z