Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of rat ileum

The aim of this study was to investigate the ability of aminoguanidine (AG) to prevent diabetes-induced changes in nitric oxide synthase- (nNOS), vasoactive intestinal polypeptide- (VIP) and noradrenaline- (NA) containing nerves of the rat ileum using immunohistochemical and biochemical techniques. Diabetes was induced in adult male Wistar rats by a single intraperitoneal injection of streptozotocin (65 mg/kg). AG was administered in the drinking water to control (1.8 g/l) and diabetic (0.9 g/l) rats over a period of 8 weeks. Diabetes caused a significant increase in the thickness of nNOS-containing nerve fibres (p<0.001) in the circular muscle, in nNOS activity (p<0.05) and in the size distribution of nNOS-containing myenteric neurons (p<0.001). The thickness of VIP-containing nerve fibres was significantly greater (p<0.01) and there was a significant increase in varicosity size (p<0.01) and proportion of VIP-positive myenteric neurons (p<0.01) in diabetes. NA levels were significantly reduced (p<0.01) and the size of varicosities containing tyrosine hydroxylase (TH) was significantly increased (p<0.001) in diabetes. AG treatment completely or partially prevented the diabetes-induced increase in nNOS activity, in VIP-containing varicosity size, and in fibre width of both VIP- and nNOS-containing fibres in the circular muscle but had no effect on the diabetes-induced increase in nNOS-containing neuronal size or proportion of VIP-containing myenteric neurons. In contrast to VIP, AG treatment had no effect on the increase in TH-containing varicosity size in diabetes and also failed to prevent the decrease in NA levels induced by diabetes. These results indicate that AG treatment for neuropathy is not equally effective for all autonomic nerves supplying the ileum and that diabetes-induced changes in NA-containing nerves are particularly difficult to treat.     

Comparative accuracy of magnetic resonance imaging and ultrasonography in confirming clinically diagnosed patellar tendinopathy

BACKGROUND: Diagnosis of patellar tendinopathy is based primarily on clinical examination; however, it is commonplace to image the patellar tendon for diagnosis confirmation, with the imaging modalities of choice being magnetic resonance imaging (MRI) and ultrasonography (US). The comparative accuracy of these modalities has not been established. HYPOTHESIS: Magnetic resonance imaging and US have good (>80%) accuracy and show substantial agreement in confirming clinically diagnosed patellar tendinopathy. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Magnetic resonance imaging and US (gray scale [GS-US] and color Doppler [CD-US]) features of 30 participants with clinically diagnosed patellar tendinopathy and 33 activity-matched, asymptomatic participants were prospectively compared. Accuracy, sensitivity, specificity, positive and negative predictive values, and the likelihood of positive and negative test results were determined for each technique. RESULTS: The accuracy of MRI, GS-US, and CD-US was 70%, 83%, and 83%, respectively (P = .04; MRI vs GS-US). The likelihood of positive MRI, GS-US, and CD-US was 3.1, 4.8, and 11.6, respectively. The MRI and GS-US had equivalent specificity (82% vs 82%; P = 1.00); however, the sensitivity of GS-US was greater than MRI (87% vs 57%; P = .01). Sensitivity (70% vs 87%; P = .06) and specificity (94% vs 82%; P = .10) did not differ between CD-US and GS-US. CONCLUSIONS: Ultrasonography was more accurate than MRI in confirming clinically diagnosed patellar tendinopathy. GS-US and CD-US may represent the best combination for confirming clinically diagnosed patellar tendinopathy because GS-US had the greatest sensitivity, while a positive CD-US test result indicated a strong likelihood an individual was symptomatic.     

Cytogenetic anchoring of radiation hybrid and virtual maps of sheep chromosome X and comparison of X chromosomes in sheep, cattle, and human

A comprehensive physical map was generated for Ovis aries chromosome X (OARX) based on a cytogenomics approach. DNA probes were prepared from bacterial artificial chromosome (BAC) clones from the CHORI-243 sheep library and were assigned to G-banded metaphase spreads via fluorescence in-situ hybridization (FISH). A total of 22 BACs gave a single hybridization signal to the X chromosome and were assigned out of 32 tested. The positioned BACs contained 16 genes and a microsatellite marker which represent new cytogenetically mapped loci in the sheep genome. The gene and microsatellite loci serve to anchor between the existing radiation hybrid (RH) and virtual sheep genome (VSG) maps to the cytogenetic OARX map, whilst the BACs themselves also serve as anchors between the VSG and the cytogenetic maps. An additional 17 links between the RH and cytogenetic maps are provided by BAC end sequence (BES) derived markers that have also been positioned on the RH map. Comparison of the map orders for the cytogenetic, RH, and virtual maps reveals that the orders for the cytogenetic and RH maps are most similar, with only one locus, represented by BAC CH243-330E18, mapping to relatively different positions. Several discrepancies, including an inverted segment are found when comparing both the cytogenetic and RH maps with the virtual map. These discrepancies highlight the value of using physical mapping methods to inform the process of future in silico map construction. A detailed comparative analysis of sheep, human, and cattle mapping data allowed the construction of a comparative map that confirms and expands the knowledge about evolutionary conservation and break points between the X chromosomes of the three mammalian species. Accession numbers: Sequence data from this article have been deposited with the GenBank Data Library under Accession Nos. FJ853178–FJ853188 and FJ868495–FJ868499.     

Site and Clinical Significance of Alloscardovia omnicolens and Bifidobacterium Species Isolated in the Clinical Laboratory

Most of the members of the genus Bifidobacterium, including the related organism Alloscardovia omnicolens, are inhabitants of the gastrointestinal tract and oral cavity of humans and animals and have been considered nonpathogenic for humans. However, the actual site of isolation and the clinical significance of A. omnicolens and of Bifidobacterium species are unclear. This may be due in part to the difficulties in distinguishing these organisms from other genera such as Actinomyces. To determine the potential disease-causing role of these organisms, we analyzed the clinical significance of 15 A. omnicolens and Bifidobacterium isolates identified by 16S rRNA gene sequencing from a clinical laboratory. All of the organisms in this study were isolated from sterile sites or in significant numbers by standard clinical microbiological culture methods. Our 15 clinical strains fit into only four species: A. omnicolens (five isolates), Bifidobacterium scardovii (four isolates), B. longum (two isolates), and B. breve (four isolates). All five A. omnicolens isolates, one of the B. breve isolates, and three of the four B. scardovii isolates were cultured from urine at 10⁵ CFU/ml. One B. scardovii isolate was from a patient with a genitourinary tract wound infection, two B. longum isolates were from abdominal wounds, and three B. breve isolates were from blood cultures. This study enlarges the spectrum of diseases and clinical sources associated with A. omnicolens and Bifidobacterium species and addresses identification problems.Many bifidobacteria are reported as commensals in humans, particularly in the gastrointestinal tract and the oral cavity (1, 12). Bifidobacteria are also reported as present in other ecological niches, such as the intestinal tracts of insects and other animals, in sewage, and in food (1, 12). It has been proposed that bifidobacteria are important for the health of the human gastrointestinal tract (2, 5). Some of the species, such as Bifidobacterium breve, B. longum, B. infantis, and B. lactis, are used as probiotics for putative health benefits in the human gastrointestinal tract (2, 5). The actual impact of the ingestion of probiotics is still unclear. It is also not clear whether species which are used as probiotics are different from normal flora species that have been associated with disease.The clinical significance of bifidobacteria is also unknown. Since these organisms appear to be important for the health of the human gastrointestinal tract, they have long been thought to be nonpathogenic. Three species, B. dentium, B. inopinatum, and B. denticolens, have been found in dental caries, and B. dentium may actually contribute to pathogenicity in these cases (4, 10). B. inopinatum and B. denticolens have since been renamed Scardovia inopinatum and Parascardovia denticolens, respectively (8). B. scardovii has been isolated from human blood, urine, and a hip specimen, but its clinical relevance is unknown (6). Alloscardovia omnicolens is related to bifidobacteria and has been isolated from urine, blood, the oral cavity, a urethral specimen, a tonsil specimen, and a lung and aortic abscess; however, actual clinical significance in these cases is not clear (7). However, Bifidobacterium species and A. omnicolens are difficult to identify and may be missed in specimens by many laboratories. In this study, we correlated the associated diseases and source of site of clinical isolate with the genetic identification for strains of A. omnicolens and Bifidobacterium species and discuss the pathogenic potential of these organisms.     

Cortico-limbic response to personally challenging emotional stimuli after complete recovery from depression

People vulnerable to depression are at increased risk of relapse if they live in highly critical family environments. To explore this link, we used neuroimaging methods to examine cortico-limbic responding to personal criticisms in healthy participants and participants with known vulnerability to major depression. Healthy controls and fully recovered participants with a past history of major depression were scanned while they heard praising, critical, and neutral comments from their own mothers. Prior to scanning, the formerly depressed and the control participants were indistinguishable with respect to self-reported positive, negative, or anxious mood. They also reported similar mood changes after being praised or criticized. However, formerly depressed participants responded to criticism with greater activation in the amygdala and less activation in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) than did controls. During praise and neutral commentary, amygdala activation was comparable in both groups, although lower levels of activation in the DLPFC and ACC still characterized formerly depressed participants. Vulnerability to depression may be associated with abnormalities in cortico-limbic activation that are independent of mood state and that remain even after full recovery. Criticism may be a risk factor for relapse because it activates the amygdala and perturbs the affective circuitry that underlies depression.     

Family history of affective illness in schizophrenia patients: Symptoms and cognition

This study examined the relationship between having a family history of affective disorder and neuropsychological functioning and PANSS symptoms in schizophrenia patients falling into four exclusive family history groups (affective spectrum disorders, schizophrenia spectrum disorders, both, or neither). Schizophrenia patients with a family history of affective illness had the best performance on IQ tests and executive function measures. Symptoms showed fewer family history group differences. Schizophrenia patients with a family history of affective disorder may be a distinct subtype in the group of schizophrenias and may be biologically more similar to patients with serious affective disorder.     

轴索生长抑制因子DNA疫苗安全有效地防治大鼠缺血性脑中风

目的评估轴索生长抑制因子DNA疫苗(pcDNA3.1(+)-neurite growth inhibitors,pcDNA-NGIs)防治缺血性脑中风的安全性和有效性。方法肌肉注射pcDNA-NGIs后,采用改良实验性自身免疫性脑髓鞘炎记分系统、改良神经病严重程度记分和逃避作业评估神经系统炎症、感觉运动和认知缺陷;采用生物素右旋糖胺追踪皮质红核投射的新生轴索。结果pcDNA-NGIs免疫不会引起神经系统炎症和感觉运动缺陷;阻塞大脑中动脉之前或之后进行pcDNA-NGIs免疫可增加皮质红核投射的新生纤维数(P=0.018)并削弱缺血性脑中风的感觉运动缺陷(P=0.042)。结论pcDNA-NGIs免疫不会使健康大鼠产生神经炎症和神经病症状,但可促进中风大鼠的神经再生和感觉运动功能恢复。