Silent cerebral infarction in patients with type 2 diabetic nephropathy. Effects of antiplatelet drug dilazep dihydrochloride

BACKGROUND: To determine whether diabetic nephropathy is a risk factor for silent cerebral infarction and whether antiplatelet drug dilazep dihydrochloride decreases the occurrence of silent cerebral infarction in type 2 diabetes patients with microalbuminuria. METHODS: Two hundred four type 2 diabetes patients (124 men, 80 women; age, median 56 years, range 42-74 years) and 60 healthy age-matched subjects (no diabetes, normal renal function) were recruited for brain magnetic resonance imaging. The diabetes patients included 40 without nephropathy (group A), 42 with microalbuminuria (20-200 microg/min) (group B), 44 with macroalbuminuria (>200 microg/min) and normal renal function (blood creatinine <132.7 micromol/L) (group C), 33 with chronic renal failure but not undergoing haemodialysis (blood creatinine >132.7 micromol/L; mean creatinine 335.9 micromol/L) (group D) and 45 undergoing haemodialysis (duration; median 4 years, range 3-6 years) (group E). RESULTS: Silent cerebral infarction was found in 20, 29, 34, 45, 53 and 8% of group A, B, C, D, E and control patients respectively. The incidence of silent cerebral infarction was increased with diabetic nephropathy. Thirty group B patients with no silent cerebral infarction were divided into two groups: (B1) 15 treated with dilazep dihydrochloride and (B2) 15 not treated with dilazep dihydrochloride. Treatment continued for 24 months. The incidence of silent cerebral infarction was significantly lower in the dilazep-treated patients (6.7%) than in the untreated patients (33.3%) (p < 0.01). CONCLUSIONS: These data suggest that diabetic renal dysfunction increases the risk of silent cerebral infarction and that dilazep dihydrochloride prevents its onset in early type 2 diabetic nephropathy patients.     

Cervical ossification of the posterior longitudinal ligament: Biomechanical analysis of the influence of static and dynamic factors

Objective

Cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) is induced by static factors, dynamic factors, or a combination of both. We used a three-dimensional finite element method (3D-FEM) to analyze the stress distributions in the cervical spinal cord under static compression, dynamic compression, or a combination of both in the context of OPLL.

Methods

Experimental conditions were established for the 3D-FEM spinal cord, lamina, and hill-shaped OPLL. To simulate static compression of the spinal cord, anterior compression at 10, 20, and 30% of the anterior–posterior diameter of the spinal cord was applied by the OPLL. To simulate dynamic compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction. To simulate combined static and dynamic compression under 10 and 20% anterior static compression, the OPLL was rotated 5°, 10°, and 15° in the flexion direction.

Results

The stress distribution in the spinal cord increased following static and dynamic compression by cervical OPLL. However, the stress distribution did not increase throughout the entire spinal cord. For combined static and dynamic compression, the stress distribution increased as the static compression increased, even for a mild range of motion (ROM).

Conclusion

Symptoms may appear under static or dynamic compression only. However, under static compression, the stress distribution increases with the ROM of the responsible level and this makes it very likely that symptoms will worsen. We conclude that cervical OPLL myelopathy is induced by static factors, dynamic factors, and a combination of both.     

Microfibril-Associated Glycoprotein-1 Controls Human Ciliary Zonule Development In Vitro

The ciliary zonule in the eye, also known as Zinn’s zonule, is composed of oxytalan fibers, which are bundles of microfibrils consisting mainly of fibrillin-1. However, it is still unclear which of the microfibril-associated molecules present in the ciliary zonule controls oxytalan fibers. Microfibril-associated glycoprotein-1 (MAGP-1) is the only microfibril-associated molecule identified in the human ciliary zonule. In the present study, we used siRNA against MAGP-1 in cultures of human non-pigmented ciliary epithelial cells to examine the extracellular deposition and appearance of fibrillin-1 employing Western blotting and immunofluorescence. MAGP-1 suppression led to a reduction of fibrillin-1 deposition. Immunofluorescence also confirmed that RNAi-mediated down-regulation of MAGP-1 led to suppression of fiber development. These results suggest that MAGP-1 plays a crucial role in the extracellular deposition of fibrillin-1 during formation of the human ciliary zonule.     

Up‐regulation of Rac1 in the bronchial smooth muscle of murine experimental asthma

There has been considerable research on the involvement of RhoA/Rho kinase signalling in smooth muscle contractions. However, only a few reports have addressed the specific role of Rac1, which is a member of the Rho GTPase superfamily. Therefore, this study investigated the role of Rac1‐related pathways in bronchial smooth muscle (BSM) contractions. Bronchial rings isolated from mice were suspended in an organ bath, and the isometric contractions of circular smooth muscles were monitored. The phosphorylation of myosin light chains (MLCs) was analysed by immunoblotting. The Rac1 inhibitor EHT1864 inhibited carbachol (CCh)‐induced BSM contractions, although high K⁺ depolarization‐induced BSM contractions were not significantly attenuated by EHT1864. Moreover, high K⁺‐ and phorbol 12,13‐dibutyrate (PDBu; PKC activator)‐induced contractions were not attenuated by Rac1 inhibition, whereas sodium fluoride (NaF)‐induced force development was inhibited by EHT1864. The gene and protein expression of Rac1 was increased in the BSM of a murine model with antigen‐induced airway hyper‐responsiveness (AHR). In addition, an increased force of the BSM contractions in AHR was suppressed by EHT1864 treatment, suggesting that the up‐regulation of Rac1 is involved in AHR. These findings suggest that an increase in Rac1‐mediated signalling is involved in the augmented contractions of BSMs in antigen‐induced AHR mice.     

Tensile Properties and Fracture Behavior of Aluminum Alloy Foam Fabricated from Die Castings without Using Blowing Agent by Friction Stir Processing Route

Al foam has been used in a wide range of applications owing to its light weight, high energy absorption and high sound insulation. One of the promising processes for fabricating Al foam involves the use of a foamable precursor. In this study, ADC12 Al foams with porosities of 67%–78% were fabricated from Al alloy die castings without using a blowing agent by the friction stir processing route. The pore structure and tensile properties of the ADC12 foams were investigated and compared with those of commercially available ALPORAS. From X-ray computed tomography (X-ray CT) observations of the pore structure of ADC12 foams, it was found that they have smaller pores with a narrower distribution than those in ALPORAS. Tensile tests on the ADC12 foams indicated that as their porosity increased, the tensile strength and tensile strain decreased, with strong relation between the porosity, tensile strength, and tensile strain. ADC12 foams exhibited brittle fracture, whereas ALPORAS exhibited ductile fracture, which is due to the nature of the Al alloy used as the base material of the foams. By image-based finite element (FE) analysis using X-ray CT images corresponding to the tensile tests on ADC12 foams, it was shown that the fracture path of ADC12 foams observed in tensile tests and the regions of high stress obtained from FE analysis correspond to each other. Therefore, it is considered that the fracture behavior of ADC12 foams in relation to their pore structure distribution can be investigated by image-based FE analysis.