Vasomotion becomes less random as diabetes progresses in monkeys.

Please cite this paper as: Tigno, Hansen, Nawang, Shamekh, and Albano (2011). Vasomotion Becomes Less Random as Diabetes Progresses in Monkeys. Microcirculation 18(6), 429-439. OBJECTIVE: Changes in vasomotion may precede other global indices of autonomic dysfunction that track the onset and progression of diabetes. Recently, we showed that baseline spectral properties of vasomotion can discriminate among N, PreDM, and T2DM nonhuman primates. In this study, our aims were to: (i) determine the time dependence and complexity of the spectral properties of vasomotion in three metabolic groups of monkeys; (ii) examine the effects of heat-provoked vasodilatation on the power spectrum; and (iii) compare the effects of exogenous insulin on the vasomotion. MATERIALS AND METHODS: Laser Doppler flow rates were measured from the foot in 9 N, 11 PreDM, and 7 T2DM monkeys. Baseline flow was measured at 34°C, and under heat stimulation at 44°C. Euglycemic-hyperinsulinemic clamps were performed to produce acute hyperinsulinemia. The Lempel-Ziv complexity, prediction error, and covariance complexity of five-dimensional embeddings were calculated as measures of randomness. RESULTS AND CONCLUSIONS: With progression of diabetes, measures of randomness of the vasomotion progressively decreased, suggesting a progressive loss of the homeostatic capacity of the peripheral circulation to respond to environmental changes. Power spectral density among T2DM animals resided mostly in the 0- to 1.45-Hz range, which excluded the cardiac component, suggesting that with progression of the disease, regulation of flow shifts toward local rather than central (autonomic) mechanisms. Heating increased all components of the spectral power in all groups. In N, insulin increased the vasomotion contributed by endothelial, neurogenic, vascular myogenic, and respiratory processes, but diminished that due to heart rate. In contrast, in T2DM, insulin failed to stimulate the vascular myogenic and respiratory activities, but increased the neural/endothelial and heart rate components. Interestingly, acute hyperinsulinemia resulted in no significant vasomotion changes in the chronically hyperinsulinemic PreDM, suggesting yet another form of "insulin resistance" during this stage of the disease.

The nose in leprosy: immunohistology of the nasal mucosa.

A detailed study of the nose was undertaken in 40 leprosy patients with different classifications of leprosy and different durations of disease at two hospitals in Brazil. This manuscript describes the immunohistochemical data on cellular infiltrates in the nasal biopsies of those patients. It was surprising that the damage to the whole depth of the nasal mucosa, epithelium and lamina propria was considerable, as was the case in the nasal mucosa which looked relatively normal during clinical inspection. The epithelium showed large holes which looked like very extended goblet cells. Very obvious was the lack of vasoconstriction after cocaine application, and the vessels also showed a lack of staining with factor VIII, possibly indicating a disruption of the endothelium. The number of neurofilaments was extensively reduced in all leprosy groups compared to normal controls. As in the skin, an increased number of CD68+ cells was found in the lamina propria of the nasal mucosa of the lepromatous patients. Contrary to findings in the skin, in the nasal mucosa of the borderline/lepromatous patients the number of CD4+ cells was increased and the number of CD8+ cells was decreased compared to normal controls. The number of CD8+ cells tended to be more reduced when the history of leprosy was longer. It is not clear as yet whether the reduced numbers of CD8+ cells are acquired during infection or whether persons with a low number of CD8+ cells in the nose might have a higher risk of acquiring leprosy.

Vasomotor reflexes in the fingertip skin of patients with type 1 diabetes mellitus and leprosy.

Fingertip skin blood flow was measured by laser Doppler flowmetry (as LDflux) under environmental conditions promoting vasodilation in Scottish patients with diabetes mellitus and Indian patients with leprosy. The reflex control of fingertip blood flow was assessed by measuring the reduction in LDflux induced by deep inspiratory gasp (IG) and cold challenge (CC) of immersing the contralateral hand in cold water. The uncomplicated diabetic patients showed normal vasomotor reflexes and an increased, though non significant, LDflux level (p < 0.06). The patients with diabetic neuropathy had resting LDflux levels significantly less than the uncomplicated group and also had substantial impairment of both IG and CC reflexes. Those with retinopathy (but no clinically apparent neuropathy) had LDflux within the normal range, but they showed minor evidence of impairment of the vasomotor reflexes. The uncomplicated newly registered leprosy patients had reduced LDflux and substantial impairment of CC reflexes. These changes were more marked in newly registered leprosy patients with clinical evidence of neuropathy. Leprosy patients with long-standing neuropathy requiring orthopaedic treatment had LDfluxes so greatly reduced that measurement of vasomotor reflexes was not practicable. The CC reflex was more severely affected than the IG reflex and more frequently absent in leprosy patients, possibly because of associated sensory neuropathy affecting the afferent limb of this response. Thus laser Doppler flowmetry can detect impairment of reflex control of fingertip blood flow in both diabetes mellitus and leprosy, but there are functional differences in the pattern of autonomic impairment between the diseases, suggesting differences in the pathogenesis of nerve damage.