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Purpose: To estimate if newly diagnosed patients with different subphenotypes of type 2 diabetes (T2DM) or latent autoimmune diabetes of adults (LADA) differ with respect to subclinical retinal microvascular structure or diabetic retinopathy (DR)., Methods: This population-based, cross-sectional study of 340 patients (675 eyes) classified patients with recently diagnosed T2DM in different subphenotypes according to beta cell function and insulin sensitivity in to; classical (n = 218), hyperinsulinaemic (n = 86), insulinopenic (n = 20), or LADA (n = 16). Retinal 6-field images were graded according to the International Clinical DR Severity Scale by a retinal expert. Retinal microvascular structures were analysed in eyes by a semiautomatic software., Results: Median age and duration of diabetes were 58.1 (49.9; 65.5) and 0.9 (0.5; 2.4) years, respectively, and 56.8% were male. In a multivariate linear mixed model regression analysis of eyes without DR (n = 570), there was no statistically significant difference in retinal venular or arteriolar width between subtypes and patients with classical T2DM. In addition, eyes from different subphenotypes did not differ according to vessel density, tortuosity or fractal dimension. In a multivariate logistic regression model adjusted for age, sex, HbA1c, diabetes duration, body mass index, mean arterial blood pressure and history of cardiovascular disease, there was a tendency towards persons with hyperinsulinaemic T2DM to be more likely to have DR (OR 1.97, 95% CI 0.95; 4.09) compared to classical T2DM., Conclusion: We found no difference in retinal microvascular structure in patients with newly diagnosed subtypes of T2DM. However, DR may be more prevalent in newly diagnosed patients with hyperinsulinaemic T2DM compared to individuals with classical T2DM., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Cerebral ischaemia results in enhanced endothelin B (ETB ) receptor-mediated contraction and receptor protein expression in the affected cerebrovascular smooth muscle cells (SMC). Organ culture of cerebral arteries is a method to induce similar alterations in ETB receptor expression. We suggest that rapid and sustained reduction in wall tension/stretch is a possible trigger mechanism for this vascular remodelling. Isolated rat middle cerebral artery (MCA) segments were incubated in a wire myograph with or without mechanical stretch, prior to assessment of their contractile response to the selective ETB receptor agonist sarafotoxin 6c. The involvement of extracellular regulated kinase (ERK) 1/2 and focal adhesion kinase (FAK) was studied by their specific inhibitors U0126 and PF-228, respectively. Compared with their stretched counterparts, unstretched MCA segments showed a significantly increased ETB receptor-mediated contractile response after 12 hr of incubation, which was attenuated by either U0126 or PF-228. The functionally increased ETB -mediated contractility could be attributed to two different mechanisms: (i) a difference in ETB receptor localization from primarily endothelial expression to SMC expression and (ii) an increased calcium sensitivity of the SMCs due to an increased expression of the calcium channel transient receptor potential canonical 1. Collectively, our results present a possible mechanism linking lack of vessel wall stretch/tension to changes in ETB receptor-mediated contractility via triggering of an early mechanosensitive signalling pathway involving ERK1/2 and FAK signalling. A mechanism likely to be an initiating factor for the increased ETB receptor-mediated contractility found after cerebral ischaemia., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background/aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown., Methods: Using a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine receptor stimulation was studied by sensitive wire myograph., Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls. This functional increase did not seem to relate to ischemic tissue damage, inflammatory cell infiltration or the element of reperfusion. Interestingly, immunohistochemistry did not show any difference in the level of immunoreactivity towards endothelin B (ETB) receptors between groups., Conclusion: Single artery occlusion without significant visible infarct resulted in locally increased ETB, angiotensin type 1 and 5-hydroxytryptamine 1B receptor-mediated contractile responses only in segments located downstream of the occlusion site. This suggests lack of wall stress as an initiating trigger leading to regulation of contractile response after cerebral stroke., (© 2013 S. Karger AG, Basel.)

Object: Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been demonstrated in cerebral artery smooth muscles in the delayed ischemic phase after experimental SAH, and intracellular signaling via the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase 1/2 pathway has been shown to be involved in this upregulation. The aim in the present study was to determine whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and improve functional outcome after experimental SAH in rats., Methods: Subarachnoid hemorrhage was induced in male Sprague-Dawley rats by the injection of 250 μl of autologous blood into the basal cisterns. Either U0126 or vehicle was intracisternally administered at 6, 12, 24, and 36 hours after SAH. Smooth muscle ET(B) and 5-HT(1B) receptor upregulation was studied in isolated cerebral artery segments through immunohistochemical and myographic studies of contractile responses to receptor-specific agonists. Gross sensorimotor function in the rats after SAH was assessed using a rotating pole test., Results: Contractile concentration-response curves for middle cerebral artery (MCA) and basilar artery (BA) segments to endothelin-1 (ET-1) and 5-carboxamidotryptamine (5-CT) were shifted leftward for SAH-induced compared with shamoperated rats due to enhanced contractile responses to individual doses of the agonists (for example, contractile responses of the BA to 3 × 10(-10) M of ET-1 and 3 × 10(-7) M of 5-CT were 9.98 ± 5.01% and 16.75 ± 3.62% of the maximal contractile capacity, respectively, in sham-operated rats and 62.78 ± 9.9% and 45.44 ± 10.62%, respectively, in SAH-induced rats). In vivo treatment with 0.19 μg/kg U0126 normalized responses in the SAH-induced rats to levels in the sham-operated rats. Protein expression of ET(B) and 5-HT(1B) receptors in cerebrovascular smooth muscles from SAH-induced rats was increased to 175 ± 33.17% and 167.7 ± 24.74%, respectively, of the levels in sham-operated rats. Endothelin-B and 5-HT(1B) expression levels in U0126-treated SAH-induced rats were at the levels in sham-operated rats (101.9 ± 13.38% and 91.44 ± 16.75%, respectively). In a rotating pole test used to assess gross sensorimotor function on the 2nd day after surgery, sham-operated rats achieved an average score of 5.37 ± 0.23, SAH-induced rats scored 3.35 ± 0.67, and SAH-induced U0126-treated rats scored 5.00 ± 0.4., Conclusions: The authors demonstrated that experimental SAH induces upregulation of ET(B) and 5-HT(1B) receptors in cerebrovascular smooth muscles and that treatment with the MEK1/2 inhibitor U0126 abolishes this receptor upregulation. They also demonstrated that experimental SAH results in sensorimotor deficits as assessed by a rotating pole test. These deficits were alleviated by U0126 treatment, suggesting that cerebrovascular receptor upregulation is critical for the functional outcome of delayed cerebral ischemia. The authors suggest that inhibition of MEK1/2 may be a promising new SAH treatment strategy.

Introduction: The main concern of patients with low back pain is the functional limitation which the symptoms cause. Therefore it is important to find a valid tool by means of which their functional level can be assessed. The aim of this study was to validate the first Danish translation of the Roland Morris Questionnaire (RMQ), which evaluates the functional level of activity of patients with low back pain and possible sciatica. The RMQ was compared with the functional scale of a Danish functional and pain level questionnaire, The Low Back Pain Rating Scale (RS), and the functional scale (PF) of the SF-36., Material and Methods: Independently, three professionals made a retroversion of the RMQ. Then 135 patients with lumbar disc herniation completed the RMQ, RS and the SF-36. The patients comprised 47% women and 53% men with an average age of 43 years., Results: A significant correlation between the RMQ and the other two questionnaires was found. RMQ-RS; r = 0.89, p < or = 0.001, RMQ-PF (SF-36); r = -0.88 p < or = 0.001. A Chronbach Alpha showed a value of 0.94 (scale 0-1). Differences in scores between the three questionnaires were within the 95% limits of agreement. The average RMQ score was 10% higher than the score of RS and PF (SF-36)., Conclusion: According to this study the RMQ can be used as a valid tool in the assessment of the functional level of patients with lumbar pain and previous lumbar herniation. Due to the fact that the questionnaire is fast and easy to complete, it is valid, reliable and sensitive and widely used internationally. We recommend the questionnaire to be used as a supplement to the clinical examination both in clinical practice and in research.