PubMed Health⌕ Search

Biomedical subjects

J A Beel

Publications and source records attributed to J A Beel.

6 recordsLinked to original sources

A threshold concept for cancer therapy.

Oxygen free radicals have been implicated in many disease processes, including aging and carcinogenesis, and have been associated with a variety of complications resulting from the treatment of cancer. As a result, the treatment of free radical-induced disease with antioxidants or free radical scavengers has become an important therapeutic modality. Ironically, these same oxygen free radicals also play a critical role in anti-cancer therapies. The use of antioxidants such as superoxide dismutase (SOD), in this setting, has been found to decrease the efficacy of anti-tumor therapies, which depend on free radical generation for their action. In addition, increased antioxidant activity can often be utilized by the tumor cell to favor increased growth. Therefore, the appropriate application of oxygen free radicals and antioxidants seems to be critically important in designing proper strategies for both prevention and treatment of malignant disorders. This review will summarize free radical and antioxidant regimens that have been employed to date, examine some of the problems associated with these regimens, introduce the 'threshold concept' explaining the dual effects of oxygen free radicals and antioxidants, and discuss a novel hypothesis regarding therapy that could potentially improve outcome in cancer patients.

Antioxidants↗

Detection of impaired cerebral autoregulation using spectral analysis of intracranial pressure waves.

Successful resuscitation following severe traumatic brain injury (TBI) requires rapid evaluation of intracranial pressure (ICP), cerebrovascular reactivity (autoregulation), and cerebral metabolism. During impaired autoregulation, inadequate cerebral blood flow (CBF) can lead to ischemia while excessive CBF can result in elevated ICP. Without information regarding the state of autoregulation, treatment of either situation may ameliorate one problem but exacerbate the other. It has been hypothesized that fast Fourier transform (FFT) analysis of arterial blood pressure (BP) and ICP waves can differentiate states of intact and impaired autoregulation. BP and ICP waves were recorded in canines before and after ischemic injury during arterial normotension, hypertension, and hypotension induced with dopamine or nitroprusside infusion. Transfer functions (TFn) were calculated from FFT spectra as ratios of ICP and BP harmonic peak amplitudes to distinguish states of vasoreactivity. During normotension and hypertension, autoregulation was intact and TF1 averaged 0.05. During hypotension, TF1 averaged 0.22 (8 x baseline, p < 0.010). During impaired autoregulation following ischemic injury, TF1 averaged 0.50 (18 x baseline, p < 0.010; 2 x nitroprusside levels, p < 0.01). This large difference in TF relative to baseline extended over a large range of BP (60 < BP < 180 mm Hg). Based on these data and previous results, it was estimated that TF can differentiate impaired autoregulation from effects solely related to elevated ICP or active vasodilation for ICP < 30-40 mm Hg. This suggests that for specific, but widely applicable physiologic conditions, spectral analysis can identify states of impaired autoregulation and, as an adjunct to traditional monitoring techniques, aid in acute resuscitation and prevention of secondary injury in TBI.

Animals↗

Structural properties of spinal nerve roots: biomechanics.

The biomechanics of spinal nerve roots obtained from normal and nerve-crushed mice were evaluated. Photographs and longitudinal force measurements were taken as nerve roots were elongated through mechanical failure. Proportional limit stress and strain as well as the apparent modulus were calculated from photographic and force measurements to characterize nerve root strength, elasticity, and stiffness, respectively. Resulting mechanical data were indicative of an extremely weak material. Comparisons of nerve and nerve root mechanical properties revealed major differences. While nerve root elasticity was comparable to nerve, nerve root strength was only 10% that of nerve and root stiffness was only 20% of nerve values. Differences in nerve and root mechanics are attributed to the large discrepancies in relative amounts of connective tissue. Also in sharp contrast with peripheral nerve, unilateral nerve crush produced no significant alterations in root mechanics. Comparisons of nerve and nerve root strengths suggested possible pathways for dissipation of peripherally applied forces through epineurial and dural structures.

Animals↗

Structural properties of spinal nerve roots: protein composition.

The protein compositions of dorsal and ventral spinal nerve roots were determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Protein readily soluble in sodium dodecyl sulfate (SDS) sample buffer made up 8.1% of the wet weight of dorsal and ventral roots. Spinal root protein samples consisted predominantly (60%) of myelin-associated proteins. Other major proteins including those tentatively identified as tubulin, actin, nuclear histones, and others accounted for the remainder of recovered protein. The protein constituents of nerve roots were similar to those of peripheral nerve but differed from those of spinal cord. Nerve roots and peripheral nerve were characterized by fewer major protein bands but greater concentrations of myelin proteins. Collagen which did not readily solubilize in SDS sample buffer was estimated by assaying for hydroxyproline. Nerve roots consisted of approximately 0.4% collagen by weight which was only one-fifth the amount estimated for nerve but six times more than spinal cord. It was apparent that the biomechanical frailty of roots compared with peripheral nerve might be explained by differences in the relative collagen contents of these tissues. The protein constituents of nerve roots after unilateral nerve crush were relatively stable compared with the profound changes seen in ipsilateral nerve and modest changes seen in contralateral uninjured nerve.

Animals↗

Postinjury changes in the biomechanics of nerves and roots in mice.

The biomechanical characteristics of sciatic nerve and associated spinal roots of mice were investigated. Both normal and postcrush nerve materials were tested in the same fashion using superimposed elongation, force and geometry data. The results show that nerve and roots differ considerably both in the force they sustain before failure and in the other biomechanics they exhibit. The nerves and associated structures transmit and absorb large amounts of force. The roots, in comparison, are mechanically frail but exhibit similar elongation before failure. The behavior of these elements of the nervous system are discussed with regard to implications for integrated nerve, root and spinal cord mechanical integrity.

Animals↗

Alterations in the mechanical properties of peripheral nerve following crush injury.

The mechanical properties of injured nerves have been studied. At specific times following unilateral nerve crush, the sciatic nerves of mice were tested mechanically. Photographs and longitudinal force measurements were obtained as nerve segments were elongated to mechanical failure. Stress and strain at the proportional limit and apparent elastic modulus were used as indicators of strength, elasticity and stiffness. Injury led to time-dependent increases in strength and stiffness and decreases in elasticity. These changes were apparent in both damaged and contralateral, undamaged nerves. Many of the changes appear to be related to the epineurium. Some mechanical changes in nerve could have important consequences for the integrity and function of nerves and mechanically interfaced structures.

Animals↗