The Bioperl toolkit: Perl modules for the life sciences

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Axonal degeneration plays an important role in the accumulation of disability in patients with multiple sclerosis (MS). Pathological studies have demonstrated axonal damage, particularly in areas of acute inflammation and demyelination, and in chronic lesions. Axonal loss and its progression, which is associated with neurological disability, has also been demonstrated by magnetic resonance imaging (MRI) studies. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, or damage to the axonal cytoskeleton. Inflammatory mediators, including cytokines and proteolytic enzymes may contribute to axonal damage, as may nitric oxide. Axonal destruction may also be due to immune attack directed at axonal components. The realisation that axonal degeneration is a fundamental component of MS that may occur early in the disease course should alter the approach to management and open avenues to a more targeted immunotherapy aimed at reducing the progression of disability.     

Continuous monitoring of extracellular lactate concentration by microdialysis lactography for the study of rat muscle metabolism in vivo

A method is described for the measurement and on-line monitoring of muscular extracellular lactate concentration in both anaesthetized and freely moving rats. This method is based on microdialysis sampling and lactic dehydrogenase-catalysed nicotinamide adenine dinucleotide, reduced (NADH)-fluorescence detection techniques. In vivo calibration revealed a resting extracellular lactate concentration of 1.92±0.13 mmol/l (± SEM) in the gastrocnemius muscle of adult male Wistar rats (n=6), while the average whole-blood lactate level was 0.76±0.12 mmol/l (± SEM). This measured extracellular lactate concentration was 1.73-times higher than that deduced from the arterial lactate concentration. Blocking glycolysis with iodoacetate reduced the extracellular lactate concentration to 52±6% (± SEM, n= 4) of the resting level. The extracellular lactate concentration in rat gastrocnemius muscle had increased to significantly (P0.05) different levels, 2.4±0.03 (± SEM) or 4.0±0.55 (± SEM) times the control value, 1 h after aortic clamping (n=3) or cardiac arrest (n=3), respectively. Stimulation of the sciatic nerve induced elevations of the extracellular lactate concentration in the tibialis anterior muscle which were linearly related to the recorded isometric force-time integral. We also monitored on-line the changes in extracellular lactate concentration in the tibialis anterior muscle of a swimming rat. Our results indicate that microdialysis lactate reflects also intracellular metabolism. Lactography may be a useful alternative to biopsies and nuclear magnetic resonance spectroscopy in clinical medicine and physiology for the monitoring of metabolism in vivo.     

A quantitative study in the rat on the relationship between imipramine levels in brain and serum

Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg^-1 to 15 mol kg^-1, 350 ng–5mg kg^-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or -hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2×36 mol kg^-1 (10 mg kg^-1), last dose 89 mol kg^-1 (25 mg kg^-1), 2–3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.deceased     

Wound healing activity of aqueous extract of Crotalaria verrucosa in Wistar albino rats

ObjectiveTo evaluate the wound healing effect of aqueous extract of Crotalaria verrucosa (C. verrucosa) in rats.MethodsThree wound models including incision, excision and dead space wounds were used in this study. The parameters studied were breaking strength in incision models, granulation tissue dry weight, breaking strength and hydroxyproline content in dead space wounds, percentage of wound contraction and period of epithelialization in excision wound model.ResultsTwo doses of the extract with and without dexamethasone showed significant increases in mean hydroxyproline, total protein content and dry weight of granulation tissue but it was higher with dose 800 mg/kg comparing with the control. The dexamethasone treated group showed a significant (P<0.001) reduction in the wound breaking strength when compared to control group in incision type of wound model. Coadministration of C. verrucosa with dexamethasone significantly (P<0.001) increased the breaking strength compared to the dexamethasone treated only group. In excision wound model, the percentage of the wound contraction was significantly (P<0.01) increased by two doses of test extract on all the days except the lower dose which exhibited only on 12 th, 16 th days of drug treatment and it also reversed the dexamethasone suppressed wound contraction. It significantly (P <0.001) reduced the time required for epithelialization and reversed the epithelialization delaying effect of dexamethasone (P<0.001).ConclusionsC. verrucosa was found to possess significant wound healing property. This was evident by decrease in the period of epithelialization, increase in the rate of wound contraction, skin breaking strength, and granulation tissue dry weight content. Hence C. verrucosa could be a good wound healing agent.