MR angiography of infrapopliteal arteries in patients with peripheral arterial occlusive disease by using Gadofosveset at 3.0 T: diagnostic accuracy compared with selective DSA

To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease.

Structural changes of the retina after conventional laser photocoagulation and selective retina treatment (SRT) in spectral domain OCT

Spectral domain optical coherence tomography (SD-OCT) in patients can deliver retinal cross-sectional images with high resolution. This may allow the evaluation of the extent of damage to the retinal pigment epithelium (RPE) and the neurosensory retina after laser treatment. This article aims to investigate the value of SD-OCT in comparing laser lesions produced by conventional laser photocoagulation and selective retina treatment (SRT).

Selective removal of anomeric O-acetate groups in carbohydrates using HCl04-Si02-tr

A convenient methodology has been developed for the selective removal of the anomeric acyl group of carbohydrate derivatives using HCI04-Si02 under acidic reaction conditions. Anomeric benzoyl groups can also be removed selectively following similar reaction conditions. The yields were excellent in all cases.

Mild and efficient hydrolysis of thioglycosides to glycosyl hemiacetals using N-iodosaccharin

A convenient methodology has been developed for the mild hydrolysis of thioglycosides to the corresponding hemiacetals using N-iodosaccharin without any requirement of co-activator. Most of the functional groups used for the protecting group manipulation of carbohydrates are remain unaffected under the reaction condition.

Development of an array of ion-selective microelectrodes aimed for the monitoring of extracellular ionic activities

In this study, we present the development and the characterization of a generic platform for cell culture able to monitor extracellular ionic activities (K+, NH4+) for real-time monitoring of cell-based responses, such as necrosis, apoptosis, or differentiation. The platform for cell culture is equipped with an array of 16 silicon nitride micropipet-based ion-selective microelectrodes with a diameter of either 2 or 6 microm. This array is located at the bottom of a 200-microm-wide and 350-microm-deep microwell where the cells are cultured. The characterization of the ion-selective microelectrode arrays in different standard and physiological solutions is presented. Near-Nernstian slopes were obtained for potassium- (58.6 +/- 0.8 mV/pK, n = 15) and ammonium-selective microelectrodes (59.4 +/- 3.9 mV/pNH4, n = 13). The calibration curves were highly reproducible and showed an average drift of 4.4 +/- 2.3 mV/h (n = 10). Long-term behavior and response after immersion in physiological solutions are also presented. The lifetime of the sensors was found to be extremely long with a high recovery rate.

Selective iNOS-inhibition does not influence apoptosis in ruptured canine cranial cruciate ligaments

Abnormal patterns of cell death, including increased apoptosis, can influence homeostasis of ligaments and could be involved in the pathogenesis of cranial cruciate ligament (CCL) rupture. Increased nitric oxide (NO) production has been implicated as a stimulus to increased apoptosis in articular cartilage. This study investigated apoptotic cell death in ruptured canine CCL (CCL group, n = 15), in ruptured CCL of dogs treated with oral L-N6-(1-iminoethyl)-lysine (L-NIL), a selective NO-synthetase(NOS)-inhibitor, (L-NIL group, n = 15) and compared the results with normal canine CCL (control group, n = 10). Orally administered L-NIL at a dosage of 25mg/m2 of body surface area was effective in inhibiting NO production in the articular cartilage of dogs in the L-NIL group, but it did not significantly influence the increased quantity of apoptotic cells found in ruptured CCL specimens. The results of this study suggest that apoptosis of ligamentocytes in the canine CCL is not primarily influenced by increased NO production within the stifle joint.

Non-selective cutaneous sensory neurectomy as an alternative treatment for auto-mutilation lesion following arthrodesis in three dogs

OBJECTIVE: To describe an alternative method for the treatment of non-responsive self-mutilation injuries in three dogs after carpal/tarsal arthrodesis. STUDY DESIGN: Case series ANIMALS: Two dogs with carpal injury and one dog with tarsal injury treated by arthrodesis METHODS: All dogs developed self-mutilation injuries due to licking and/or chewing of the toes within 21-52 days of surgery. Clinical signs did not resolve within one week after conservative treatment with wound debridement and protective bandages. Following general anaesthesia, a deep horseshoe-shaped skin incision, including the subdermal tissue, was performed proximal to the self-mutilation injury transecting the sensory cutaneous afferent nerves. The skin incision was closed with simple interrupted sutures. RESULTS: All wounds healed without complication. Self-mutilation resolved completely within 24 hours after surgery in all dogs. No recurrence was observed (5 months to 3 years). CONCLUSION: Non-selective cutaneous sensory neurectomy may lead to resolution of self-mutilation following arthrodesis in dogs. CLINICAL RELEVANCE: Failure of conservative treatment in self-mutilation injuries often leads to toe or limb amputation as a last resort. The technique described in this case series is a simple procedure that should be considered prior to amputation. The outcome of this procedure in dogs self-multilating due to neurological or behavioral disturbances unrelated to carpal or tarsal arthrodesis is not known.

Surface quality of profile extrusion dies manufactured by Selective Laser Melting

The design of plastics profile extrusion dies becomes increasingly more complex so that conventional manufacture processes reach their limit in the die manufacture. A feasible manufacture of arbitrarily designed dies is only possible by additive manufacturing. An especially promising process is hereby the Selective Laser Melting with which metal parts with series identical mechanical properties can be produced without the need for part specific tooling or downstream sintering processes. Disadvantegeous is, however, the relatively rough surface of additively manufactured parts. Against this background, the manufacturing of an profile extrusion die by Selective Laser Melting and the plastics profile surface quality, that can be achieved with such dies, is investigated. For this purpose, profiles are extruded both with an additively manufactured die and a conventionally milled sample of the same die geometry. In case of the additively manufactured die a concept for the surface finishing of the flow channel is required, which can be applied to arbitrarily shaped geometries. Therefore, two different reworking processes are applied only to the die land of the flow channel. The comparison of the surface roughnesses shows that the additively manufactured die with a polished die land delivers the same surface quality as the conventional die.

The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain

The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB2). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB2 is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB2 receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB2 agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption).

Mammals are unable to synthesize cobalamin or vitamin B12 and rely on the uptake of dietary cobalamin. The cubam receptor expressed on the intestinal endothelium is required for the uptake of cobalamin from the gut. Cubam is composed of two protein subunits, amnionless and cubilin, which are encoded by the AMN and CUBN genes respectively. Loss-of-function mutations in either the AMN or the CUBN gene lead to hereditary selective cobalamin malabsorption or Imerslund-Gräsbeck syndrome (IGS). We investigated Beagles with IGS and resequenced the whole genome of one affected Beagle at 15× coverage. The analysis of the AMN and CUBN candidate genes revealed a homozygous deletion of a single cytosine in exon 8 of the CUBN gene (c.786delC). This deletion leads to a frameshift and early premature stop codon (p.Asp262Glufs*47) and is, thus, predicted to represent a complete loss-of-function allele. We tested three IGS-affected and 89 control Beagles and found perfect association between the IGS phenotype and the CUBN:c.786delC variant. Given the known role of cubilin in cobalamin transport, which has been firmly established in humans and dogs, our data strongly suggest that the CUBN:c.786delC variant is causing IGS in the investigated Beagles.

A frameshift mutation in the cubilin gene (CUBN) in Border Collies with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption).

Imerslund-Gräsbeck syndrome (IGS) or selective cobalamin malabsorption has been described in humans and dogs. IGS occurs in Border Collies and is inherited as a monogenic autosomal recessive trait in this breed. Using 7 IGS cases and 7 non-affected controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 3.53 Mb interval on chromosome 2. We re-sequenced the genome of one affected dog at ∼10× coverage and detected 17 non-synonymous variants in the critical interval. Two of these non-synonymous variants were in the cubilin gene (CUBN), which is known to play an essential role in cobalamin uptake from the ileum. We tested these two CUBN variants for association with IGS in larger cohorts of dogs and found that only one of them was perfectly associated with the phenotype. This variant, a single base pair deletion (c.8392delC), is predicted to cause a frameshift and premature stop codon in the CUBN gene. The resulting mutant open reading frame is 821 codons shorter than the wildtype open reading frame (p.Q2798Rfs*3). Interestingly, we observed an additional nonsense mutation in the MRC1 gene encoding the mannose receptor, C type 1, which was in perfect linkage disequilibrium with the CUBN frameshift mutation. Based on our genetic data and the known role of CUBN for cobalamin uptake we conclude that the identified CUBN frameshift mutation is most likely causative for IGS in Border Collies.