An overview of podiatric biomechanics theory and its relation to selected gait dysfunction

This paper introduces the ‘foot function’ approach used by podiatrists in the treatment of lower limb musculoskeletal dysfunction. The aim is to demonstrate how podiatric theory has evolved its own perspective of mechanisms relating to normal and abnormal locomotion. Three individual podiatric paradigms are discussed, and a further theory allowing a working simplification of theory is introduced. Finally, an example of gait abnormality is discussed in relation to podiatric and physiotherapy perspectives.An insight into podiatric theory should enable therapists working within this field to develop a more holistic and multidisciplinary approach. It is the view of the authors that a closer working relationship between physiotherapists and podiatrists with an interest in movement dysfunction provides a better quality service for appropriate patients.     

L-694,247: a potent 5-HT1D receptor agonist.

1. The 5-hydroxytryptamine (5-HT) receptor binding selectivity profile of a novel, potent 5-HT1D receptor agonist, L-694,247 (2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl ]- 1H-indole-3-yl]ethylamine) was assessed and compared with that of the 5-HT1-like receptor agonist, sumatriptan. 2. L-694,247 had an affinity (pIC50) of 10.03 at the 5-HT1D binding site and 9.08 at the 5-HT1B binding site (sumatriptan: pIC50 values 8.22 and 5.94 respectively). L-694,247 retained good selectivity with respect to the 5-HT1A binding site (pIC50 = 8.64), the 5-HT1C binding site (6.42), the 5-HT2 binding site (6.50) and the 5-HT1E binding site (5.66). The pIC50 values for sumatriptan at these radioligand binding sites were 6.14, 5.0, < 5.0 and 5.64 respectively. Both L-694,247 and sumatriptan were essentially inactive at the 5-HT3 recognition site. 3. L-694,247, like sumatriptan, displayed a similar efficacy to 5-HT in inhibiting forskolin-stimulated adenylyl cyclase in guinea-pig substantia nigra although L-694,247 (pEC50 = 9.1) was more potent than sumatriptan (6.2) in this 5-HT1D receptor mediated functional response. L-694,247 (pEC50 = 9.4) was also more potent than sumatriptan (6.5) in a second 5-HT1D receptor mediated functional response, the inhibition of K(+)-evoked [3H]-5-HT release from guinea-pig frontal cortex slices.(ABSTRACT TRUNCATED AT 250 WORDS)     

T cells respond preferentially to antigens that are similar to self H-2.

We have constructed bone marrow irradiation chimeras to investigate the influence of self antigens on the specificity of the T lymphocyte receptor repertoire. Bone marrow cells from (A X B)F1 mice heterozygous for the major histocompatibility genes were allowed to mature into T cells in irradiated parent A or parent B strains. More than 8 weeks after irradiation, when the lymphoid system had regenerated from the F1 stem cells, the degree of T cell reactivity to mutant major histocompatibility antigens, A', was assessed. It was found that T cells that had matured in the irradiated A mice, [F1 leads to A] chimeras, responded better to A' antigen than did T cells from the [F1 leads to B] chimeras. Because the mutant histocompatibility antigen A' is very similar in structure to A, differing only by one or a few residues, this suggests that the T cell repertoire in [F1 leads to parent] chimeras reacts preferentially with foreign antigens that are slight variants of the self antigens expressed on radiation-resistant cells--probably cells in the thymus.     

Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.     

Two indices of functional damage of the artery wall parallel the time course of irreversible narrowing in experimental vasospasm in the rabbit

Autologous blood placed around the basilar artery caused angiographic narrowing with a biphasic time course. The first immediate phase was reversed by intraarterial papaverine; the second exhibited an increasing component of narrowing which was papaverine-resistant. In vitro studies showed that vessels became increasingly stiffer, less capable to develop active tone, and less responsive to vasoconstrictors and vasodilators. The papaverine-resistant component of angiographic narrowing (in vivo) could be directly correlated with loss of contractility and increased artery wall stiffness (in vitro).     

Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin.

1. Capsazepine is a synthetic analogue of the sensory neurone excitotoxin, capsaicin. The present study shows the capsazepine acts as a competitive antagonist of capsaicin. 2. Capsazepine (10 microM) reversibly reduced or abolished the current response to capsaicin (500 nM) of voltage-clamped dorsal root ganglion (DRG) neurones from rats. In contrast, the responses to 50 microM gamma-aminobutyric acid (GABA) and 5 microM adenosine 5'-triphosphate (ATP) were unaffected. 3. The effects of capsazepine were examined quantitatively with radioactive ion flux experiments. Capsazepine inhibited the capsaicin (500 nM)-induced 45Ca2+ uptake in cultures of rat DRG neurones with an IC50 of 420 +/- 46 nM (mean +/- s.e.mean, n = 6). The 45Ca2+ uptake evoked by resiniferatoxin (RTX), a potent capsaicin-like agonist was also inhibited. (Log concentration)-effect curves for RTX (0.3 nM-1 microM) were shifted in a competitive manner by capsazepine. The Schild plot of the data had a slope of 1.08 +/- 0.15 (s.e.) and gave an apparent Kd estimate for capsazepine of 220 nM (95% confidence limits, 57-400 nM). 4. Capsazepine also inhibited the capsaicin- and RTX-evoked efflux of 86Rb+ from cultured DRG neurones. The inhibition appeared to be competitive and Schild plots yielded apparent Kd estimates of 148 nM (95% confidence limits, 30-332 nM) with capsaicin as the agonist and 107 nM (95% confidence limits, 49-162 nM) with RTX as agonist. 5. A similar competitive inhibition by capsazepine was seen for capsaicin-induced [14C]-guanidinium efflux from segments of adult rat vagus nerves (apparent Kd = 690 nM; 95% confidence limits, 63 nM-1.45 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。