Endoneurial localisation of microvascular damage in human diabetic neuropathy

Twenty diabetic patients with neuropathy underwent clinical and neurophysiological evaluation together with a detailed morphometric assessment of capillary pathology in endoneurial and epineurial microvascular beds of the sural nerve. Morphological data were compared with ten non-diabetic control subjects. There were no significant differences in control subjects between basement membrane area, endothelial cell area, endothelial cell profile number or luminal area of endoneurial when compared with epineurial capillaries. In contrast, when compared with epineurial capillaries, endoneurial capillaries from diabetic patients demonstrated a significant increase in basement membrane (p < 0.001) and endothelial cell (p < 0.001) area and a significant reduction in luminal area (p < 0.001). There was no significant difference in endothelial cell profile number between endoneurial and epineurial capillaries amongst diabetic patients. Previous studies have demonstrated a good correlation between the degree of microangiopathy and measures of neuropathic severity. In the present study increased endoneurial capillary basement membrane area was significantly related to reduced peroneal nerve conduction velocity (p < 0.001), myelinated fibre density (p < 0.001) and elevated vibration (p < 0.05) and thermal (p < 0.001) perception. Increased endothelial cell area and reduced luminal size were related to a reduced peroneal nerve conduction (p < 0.05, p < 0.01, respectively), reduced myelinated fibre density (p < 0.05, p < 0.01) and elevated thermal perception (p < 0.05, p < 0.001). Epineurial capillary basement membrane, endothelial cell and luminal area failed to relate to measures of neuropathic severity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thymosin beta-10 accelerates apoptosis

The 5 Kd (MW), retinoic acid responsive thymosin beta-10 protein is expressed at relatively high levels in embryonic tissues, and its mRNA is abundant in a variety of tumors and tumor cell lines. Recently this protein (together with other members of the same protein family) was found to be a major intracellular G-actin binding protein. In the present study, plasmid-driven overexpression of thymosin beta-10 gene results in increased susceptibility of permanently transfected fibroblasts to undergo apoptosis. Conversely, knockout of the endogenous gene via overexpression of the antisense mRNA inhibited cell death induced by TNF-alpha and calcium ionophore A23187. Differential expression of thymosin beta-10 influenced cell proliferation, cell morphology, and expression/distribution of the antiapoptotic protein bcl-2. The presence of increased cytoplasmic thymosin beta-10 precipitated significant disruption of phalloidin-stained actin stress fibers while knockout of thymosin expression promoted F-actin assembly. These and other observations suggest that thymosin beta-10 (a) plays a significant and possibly obligatory role in cellular processes controlling apoptosis possibly by acting as an actin-mediated tumor suppressor, (b) perhaps functions as a neoapoptotic influence during embryogenesis, and (c) may mediate some of the pro-apoptotic anticancer actions of retinoids.     

A limit analysis of nonlinear elastic lateral displacements of thin-walled reinforced and prestressed beams

An incremental iterative process based on direct energy minimization is presented for a limit analysis of nonlinear elastic lateral displacements and twists of reinforced and prestressed beams. Problems encountered with the constitutive relations are discussed and two possible material models are presented.     

Ambient, biological, and biological effect monitoring of exposure to polycyclic aromatic hydrocarbons (PAHs)

A novel strategy was utilised to assess the risk to health from exposure to polycyclic aromatic hydrocarbons (PAHs). Ambient monitoring was carried out by personal sampling. Urinary thioethers (UTh) and urinary 1-hydroxypyrene (1-HP) were utilised for biological monitoring. Urinary d-glucaric acid (UDGA) and sister chromatid exchange (SCE) in peripheral blood lymphocytes were used as biological effect markers. The population was categorised into exposed and control groups according to the external dose of PAHs. The excretion of 1-HP in the controls over the 3-day period showed a relatively stable baseline, while the exposed showed a significant increase over the same period of time. SCE frequency in the exposed population was significantly different from controls.     

Transcutaneous balloon angioplasty in the treatment of subclavian steal syndrome. Characteristics of vertebral basal flow with transcranial Doppler technique

Subclavian steal syndrome (SSS) appears when the origin of the subclavian artery (SA) is occluded or stenosed. Introduction of transcranial Doppler sonography (TCD) provided an opportunity to evaluate parameters of the blood flow in the vertebral (VA) and basilar artery (BA). Measurements of blood flow velocities performed at rest and after the brachial hyperemia test allow one to classify hemodynamic types of SSS. The aim of the study was to categorize types of steal and to compare the differences of flow patterns before and after percutaneous transluminal SA balloon angioplasty (SA-PTA). Fourty-eight patients with angiographically confirmed SSS (aged from 27 to 68 years, mean 53; 2/1 f/m ratio) were examined with 2 MHz range-gated, pulsed transcranial Doppler device (TC 2-64B EME). Both VA and BA were evaluated by the transoccipital approach at rest and during the brachial hyperemia. In 5 cases (10.4%) permanent reversal blood flow in the BA was observed (complete basilar steal). In flow in the BA blood flow was in the normal direction at rest and altered (reversed or decreased) when induced with brachial hyperemia test (transient basilar steal). In the next 14 patients (29.2%) permanently reversed VA blood flow was observed with only a slight or no alterations of the BA flow after the hyperemia test (complete vertebral steal). In the last 19 cases (39.6%) alterations of the VA blood flow without changes in BA flow were observed (latent vertebral steal). Between 1991 and 1994 twenty seven symptomatic patients with different hemodynamic types of SSS were treated with SA-PTA. TCD evaluation of VA's and BA using the hyperemia test was performed before, 3 to 7 days and 3 months after morphologically and hemodynamically successful subclavian artery balloon PTA. Normal results of vertebrobasilar examinations were obtained in 26 cases after this procedure. In one case the latent vertebral steal was detected. The 28 months mean follow-up revealed no significant changes in TCD flow patterns recorded from VA's and BA. After collecting data of about 60 patients with SSS we examined with TCD we conclude that: in patients with a hemodynamically significant SA stenosis the presence of reversed ipsilateral VA blood flow (a radiologic steal) its not a good determinant of either the presence or type of presenting symptoms and after successful PTA or recanalisation and PTA of SA in almost all cases we examined close to normal TCD recordings in BA and VA.