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M F Engels

Publications and source records attributed to M F Engels.

2 recordsLinked to original sources

Smart screening: approaches to efficient HTS.

Faced with the prospect of a rising number of potential drug targets and given almost unlimited access to internal and external chemistry resources, the 'brute-force' approach to high-throughput screening (HTS) is becoming increasingly unattractive. Pharmaceutical companies realize that they have both to increase the scope of screening experiments and improve on the efficiency of the screening process per se. In acknowledging this development, hybrid screening strategies have been suggested that unite in silico and in vitro screening in one integrated process. The partnering of both screening approaches in one process is believed to exploit the potential of HTS in much smarter and more cost-efficient ways. This review will describe some recent applications of this new screening paradigm and discuss the impact of integrating these novel strategies in the drug discovery process.

Computational Biology↗

Urine protein excretion and swimming events.

To determine total urinary protein, albumin (ALB), and beta 2-microglobulin (beta 2m) excretion rates in relation to different speeds, 12 males were studied while swimming distances of 100, 600, and 2,000 m at maximal speed. Venous blood lactate concentrations rose to 16.1, 11.6, and 4.5 mmol.l-1 after the 100, 600, and 2,000 m events, while plasma volumes were reduced by 11.3, 7.7, and 5.5%, respectively. ALB urine excretion increased to 110-120 micrograms.min-1 after the 100 and 600 m swims and to 56 micrograms.min-1 after 2,000 m (resting values: 9 micrograms.min-1). In the meantime, the beta 2m excretion rate increased 21 and 10 times the resting values, respectively, for the two shorter swims, with no change for the longer one. Progressive plasma volume reduction was associated with the increase of the protein excretion rate. As evidenced by the creatinine clearance, the glomerular filtration rate did not change for the 100 m swim but dropped by 23 and 35% for the 600 and 2,000 m ones, respectively. On the other hand, the ALB clearance increases were elevated for the three swims, while the beta 2m clearance increases were inversely related to the swimming speeds. The data showed a relationship between the rate of protein excretion and the speed of the swim, and the reduction of plasma volume. The findings could indicate a renal glomerular alteration, with an additional dysfunction of the tubular reabsorption process when the exercise load is high during swimming events.

Albuminuria↗