Targeted vessel reconstruction in non‐contrast‐enhanced steady‐state free precession angiography

Image quality in non‐contrast‐enhanced (NCE) angiograms is often limited by scan time constraints. An effective solution is to undersample angiographic acquisitions and to recover vessel images with penalized reconstructions. However, conventional methods leverage penalty terms with uniform spatial weighting, which typically yield insufficient suppression of aliasing interference and suboptimal blood/background contrast. Here we propose a two‐stage strategy where a tractographic segmentation is employed to auto‐extract vasculature maps from undersampled data. These maps are then used to incur spatially adaptive sparsity penalties on vascular and background regions. In vivo steady‐state free precession angiograms were acquired in the hand, lower leg and foot. Compared with regular non‐adaptive compressed sensing (CS) reconstructions (CS_low), the proposed strategy improves blood/background contrast by 71.3 ± 28.9% in the hand (mean ± s.d. across acceleration factors 1–8), 30.6 ± 11.3% in the lower leg and 28.1 ± 7.0% in the foot (signed‐rank test, P < 0.05 at each acceleration). The proposed targeted reconstruction can relax trade‐offs between image contrast, resolution and scan efficiency without compromising vessel depiction. Copyright © 2016 John Wiley & Sons, Ltd.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Load signals assist the generation of movement-dependent reflex reversal in the femur-tibia joint of stick insects

Reinforcement of movement is an important mechanism by which sensory feedback contributes to motor control for walking. We investigate how sensory signals from movement and load sensors interact in controlling the motor output of the stick insect femur-tibia (FT) joint. In stick insects, flexion signals from the femoral chordotonal organ (fCO) at the FT joint and load signals from the femoral campaniform sensilla (fCS) are known to individually reinforce stance-phase motor output of the FT joint by promoting flexor and inhibiting extensor motoneuron activity. We quantitatively compared the time course of inactivation in extensor tibiae motoneurons in response to selective stimulation of fCS and fCO. Stimulation of either sensor generates extensor activity in a qualitatively similar manner but with a significantly different time course and frequency of occurrence. Inactivation of extensor motoneurons arising from fCS stimulation was more reliable but more than threefold slower compared with the extensor inactivation in response to flexion signals from the fCO. In contrast, simultaneous stimulation of both sense organs produced inactivation in motoneurons with a time course typical for fCO stimulation alone, but with a frequency of occurrence characteristic for fCS stimulation. This increase in probability of occurrence was also accompanied by a delayed reactivation of the extensor motoneurons. Our results indicate for the first time that load signals from the leg affect the processing of movement-related feedback in controlling motor output.     

Curcumin ameliorates impaired insulin/IGF signalling and memory deficit in a streptozotocin-treated rat model

Increased serum insulin levels and reduced peripheral insulin activities seen in insulin resistance syndrome are associated with age-dependent cognitive impairment and Sporadic Alzheimer’s Disease (SAD), suggesting a disturbance in the insulin signalling system in the brain and possibly being one of the causes of dementia. Therefore, the streptozotocin (STZ)-induced animal may be an appropriate model for the investigation of SAD and related dementia. This study was designed to investigate the beneficial effect of Curcumin (CUR), a neuroprotective agent, on intracerebroventricular (ICV) STZ-induced cognitive impairment in rats. For this purpose, adult male Wistar rats were bilaterally ICV injected with STZ (3 mg/kg). An artificial cerebrospinal fluid (aCSF) was given to the control group (SHAM) instead of STZ on days 1 and 3. Learning and memory performance were assessed using the “passive avoidance task” and the “Morris water maze test”. After confirmation of acquisition impairment with these tests, the STZ group was divided into two subgroups: STZ + vehicle (Vh) and STZ + CUR. The rats in the SHAM and STZ + Vh groups were administered intraperitoneally with 0.5 ml Vh and the rats in the STZ + CUR group were treated intraperitoneally with CUR (300 mg kg⁻¹ day⁻¹ in Vh) for 10 days starting from the 25th day after STZ injection. The Morris water maze test was reapplied on the 35th day after STZ injection and all of the rats were sacrificed on day 36 for quantitation of IGF-1 and for histopathological evaluation. Rats in the STZ + CUR group were found to have a higher performance in cognitive tests than rats in the STZ + Vh group (P < 0.01). In parallel with the cognitive tests, IGF-1 levels were decreased in all of the STZ-injected groups (1.78 ± 0.34) compared to the SHAM group (3.46 ± 0.41). In contrast, CUR treatment significantly increased IGF-1 levels (P < 0.001). The degree of neuronal loss decreased after CUR treatment compared to the SHAM group (P < 0.02). These results clearly indicate that CUR treatment is effective in reducing the cognitive impairment caused by STZ in rats, and may be a potential therapeutic agent for altering neurodegeneration in SAD.     

Is the Cell Death in Mesial Temporal Sclerosis Apoptotic?

PURPOSE: Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures. METHODS: We searched evidence for apoptotic cell death in temporal lobes resected from drug-resistant epilepsy patients with MTS by using the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL) method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin fragment, fractin. The temporal lobe specimens were obtained from 15 patients (six women and nine men; mean age, 29 +/- 8 years). RESULTS: Unlike that in normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining neurons dispersed throughout the hippocampus proper as well as in most of the reactive astroglia. Bax immunopositivity was increased in almost all neurons. Fractin immunostaining, an indicator of caspase activity, was detected in approximately 10% of these neurons. Despite increased Bax expression and activation of caspases, we could not find evidence for DNA fragmentation by TUNEL staining. We also could not detect typical apoptotic changes in nuclear morphology by Hoechst-33258 or hematoxylin counterstaining. CONCLUSIONS: These data suggest that either apoptosis is not involved in cell loss in MTS, or a very slow rate of cell demise may have precluded detecting TUNEL-positive neurons dying through apoptosis. Increased Bax expression and activation of caspases support the latter possibility.     

N-acetylcysteine attenuates bacterial translocation after partial hepatectomy in rats

BACKGROUND: Translocating enteric bacteria have been suggested as playing a major role in the development of infections after partial hepatectomy. We investigated the effect of N-acetylcysteine (NAC) on bacterial translocation (BT) and intestinal mucosa as the first line of defense against BT. MATERIALS AND METHODS: We compared four groups of eight Sprague-Dawley male rats each: sham, control (partially hepatectomized), partial hepatectomy plus preoperative single-dose NAC, and a fourth that received partial hepatectomy with a preoperative single-dose NAC plus treatment with NAC for 2 days. Microorganism counts of tissues, lung injury score, lung tissue glutathione, and malondialdehyde levels and microscopy of intestinal mucosa were studied at the end of 48 h. RESULTS: Microorganism count in the lung and mesenteric lymph node cultures and lung injury score were significantly higher in the control group when compared with the sham, third, and fourth groups (lung: 9919.6 versus 0.0, 2912.9, 1550.0 cfu/g tissue; mesenteric lymph nodes: 8458.3 versus 0.0, 89.0, 88.9 cfu/g tissue; lung injury score: 3.25 versus 0.5, 1.13, 1.75). In the control group, the villous height of the distal ileal mucosa was significantly shorter than the sham group (65.25 versus 75.25 microm) and the difference from groups 3 and 4 was not statistically significant. Neutrophil infiltration in the distal ileal mucosa of the control group was significantly higher than the sham, third and fourth groups (3.13 versus 0.25, 0.38 and 1.0). CONCLUSIONS: The parenteral use of NAC attenuates bacterial translocation after partial hepatectomy in rats. Attenuation of the lung injury after partial hepatectomy in NAC-treated groups might be attributable to both anti-inflammatory effect and the effect on BT.     

Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients

BACKGROUND: Sleep complaints are common in end-stage renal disease. We aimed to investigate the relationship between sleep-related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels. METHODS: Predialysis serum interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels in nine patients with sleep complaints were compared with those of nine patients without sleep complaints and nine healthy controls. Patients with sleep complaints underwent polysomnography the night after HD and the following night. RESULTS: Patients with sleep complaints had significantly higher predialysis IL-1beta levels compared with those without and healthy controls (P=0.004 and P=0.000, respectively). They also had higher predialysis IL-6 and TNF-alpha levels than those without sleep complaints; however, the difference was not significant. Patients without sleep complaints had higher mean IL-6 and TNF-alpha and similar mean IL-1beta levels compared with healthy controls (P=0.001, P=0.024, P=0.26, respectively). Obstructive sleep apnoea syndrome (OSAS) was found in six out of nine (66%) patients with sleep complaints. Sleep architecture and cytokine levels did not differ between the two nights. The mean serum IL-1beta, IL-6 and TNF-alpha levels did not differ in the pre- and post-polysomnographic samples. There was no correlation between IL-1beta, IL-6 or TNF-alpha levels and the apnoea-hypopnoea index. CONCLUSIONS: Proinflammatory cytokines, IL-1beta in particular, might be associated with sleep complaints in HD patients. OSAS is not uncommon in HD patients with sleep-related complaints and sleep architecture does not appear to be effected by the HD procedure itself.