Influences of HIF-lα on Bax/Bcl-2 and VEGF expressions in rats with spinal cord injury

Hypoxia-inducible factor 1-alpha (HIF-1α) is a subunit of HIF-l and thought to be able to protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. This study aimed to investigated whether recombinant adenovirus vector over-expressing HIF-lα could affect apoptosis-related proteins (Bcl-2 and Bax) and vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model. A total of 60 male SD rats were divided into 4 groups: Sham, Control, Ad-Blank and Ad-HIF-1α groups. 1, 3, 7, 14, 28 days after surgery, the behavioral recovery was evaluated with BBB scales. Then, rats were sacrificed and the spinal cord was collected for detection of Bcl-2, Bax and VEGF expressions by immunohistochemistry. Results showed the Bcl-2, Bax, VEGF and HIF-lα expressions increased in animals with SCI, but the increase in Bcl-2, VEGF and HIF-lα expressions were higher in Ad-HIF-1α group when compared with other groups, but Bax expression decreased significantly. In addition, administration of Ad-HIF-1α significantly reduced apoptotic cells and promoted the recovery of neurological function. In conclusion, administration of Ad-HIF-1α after SCI could ameliorate neuronal apoptosis and promote angiogenesis in rats. Our study provides a basis for further exploration of the relationship between HIF1α and SCI.     

The levels of liver enzymes and atypical lymphocytes are higher in youth patients with infectious mononucleosis than in preschool children

Background/Aims

Infectious mononucleosis (IM) is the clinical presentation of primary infection with Epstein-Barr virus. Although the literature contains a massive amount of information on IM, most of this is related specifically to only children or adults separately. In order to distinguish any differences between preschool children and youth patients, we retrospectively analyzed their demographic and clinical features.

Methods

Records of patients hospitalized from December 2001 to September 2011 with a diagnosis of IM were retrieved from Peking University First Hospital, which is a tertiary teaching hospital in Beijing. The demographic data and clinical characteristics were collected.

Results

IM was diagnosed in 287 patients during this 10-year period, with incidence peaks among preschool children (≤7 years old, 130/287, 45.3%) and youth patients (>15 and <24 years old, 101/287, 35.2%). Although the complaints at admission did not differ between these two patient groups, the incidence of clinical signs (tonsillopharyngitis, lymphadenopathy, hepatomegaly, and edema of the eyelids) was much higher in preschool children. The incidence of liver lesion and percentage of atypical lymphocytes were significantly higher in the youth group (P<0.001), and the average hospital stay was longer in this group. Pneumonia was the most common complication, and there was no case of mortality.

Conclusions

The incidence of IM peaks among preschool children and youth patients in Beijing, China. The levels of liver enzymes and atypical lymphocytes increase with age.     

Quality evaluation of the available Internet information regarding pain during orthodontic treatment

Objective:To investigate the quality of the data disseminated via the Internet regarding pain experienced by orthodontic patients.Materials and Methods:A systematic online search was performed for ‘orthodontic pain’ and ‘braces pain’ separately using five search engines. The first 25 results from each search term–engine combination were pooled for analysis. After excluding advertising sites, discussion groups, video feeds, and links to scientific articles, 25 Web pages were evaluated in terms of accuracy, readability, accessibility, usability, and reliability using recommended research methodology; reference textbook material, the Flesch Reading Ease Score; and the LIDA instrument. Author and information details were also recorded.Results:Overall, the results indicated a variable quality of the available informational material. Although the readability of the Web sites was generally acceptable, the individual LIDA categories were rated of medium or low quality, with average scores ranging from 16.9% to 86.2%. The orthodontic relevance of the Web sites was not accompanied by the highest assessment results, and vice versa.Conclusions:The quality of the orthodontic pain information cited by Web sources appears to be highly variable. Further structural development of health information technology along with public referral to reliable sources by specialists are recommended.     

The influence of the segmentation process on 3D measurements from cone beam computed tomography-derived surface models

To compare the accuracy of linear and angular measurements between cephalometric and anatomic landmarks on surface models derived from 3D cone beam computed tomography (CBCT) with two different segmentation protocols was the aim of this study. CBCT scans were made of cadaver heads and 3D surface models were created of the mandible using two different segmentation protocols. A high-resolution laser surface scanner was used to make a 3D model of the macerated mandibles. Twenty linear measurements at 15 anatomic and cephalometric landmarks between the laser surface scan and the 3D models generated from the two segmentation protocols (commercial segmentation (CS) and doctor’s segmentation (DS) groups) were measured. The interobserver agreement for all the measurements of the all three techniques was excellent (intraclass correlation coefficient 0.97–1.00). The results are for both groups very accurate, but only for the measurements on the condyle and lingual part of the mandible, the measurements in the CS group is slightly more accurate than the DS group. 3D surface models produced by CBCT are very accurate but slightly inferior to reality when threshold-based methods are used. Differences in the segmentation process resulted in significant clinical differences between the measurements. Care has to be taken when drawing conclusions from measurements and comparisons made from different segmentations, especially at the condylar region and the lingual side of the mandible.     

安氏Ⅱ类亚类错畸形的病因及其矫治

安氏Ⅱ类亚类错畸形是临床中较为常见的一种错畸形,是在临床治疗中最为复杂和困难的错类型之一。临床中可以通过多种方法,来协调以使双侧达到良好磨牙关系。正畸医师应根据患者年龄、错的严重程度、合并的错类型、患者配合程度等选择不同的方法,以达到最佳效果。本文就近年来对安氏Ⅱ类亚类错畸形的病因、临床表现及治疗方法等的相关研究作一综述。     

Cathepsin K Knockout Mitigates High-Fat Diet–Induced Cardiac Hypertrophy and Contractile Dysfunction

The cysteine protease cathepsin K has been implicated in pathogenesis of cardiovascular disease. We hypothesized that ablation of cathepsin K protects against obesity-associated cardiac dysfunction. Wild-type mice fed a high-fat diet exhibited elevated heart weight, enlarged cardiomyocytes, increased left ventricular wall thickness, and decreased fractional shortening. All these changes were reconciled in cathepsin K knockout mice. Cathepsin K knockout partly reversed the impaired cardiomyocyte contractility and dysregulated calcium handling associated with high-fat diet. Additionally, cathepsin K knockout alleviated whole-body glucose intolerance and improved insulin-stimulated Akt phosphorylation in high-fat diet–fed mice. High-fat feeding increased the expression of cardiac hypertrophic proteins and apoptotic markers, which were inhibited by cathepsin K knockout. Furthermore, high-fat feeding resulted in cathepsin K release from lysosomes into the cytoplasm. In H9c2 myoblasts, silencing of cathepsin K inhibited palmitic acid–induced release of cytochrome c from mitochondria and expression of proapoptotic signaling molecules. Collectively, our data indicate that cathepsin K contributes to the development of obesity-associated cardiac hypertrophy and may represent a potential target for the treatment to obesity-associated cardiac anomalies.Obesity is an emerging health problem worldwide and is an independent risk factor for the pathogenesis of cardiovascular disease (1–3). Uncorrected obesity predisposes individuals to myocardial damage characterized as cardiac hypertrophy and contractile dysfunction (4–6). Although several theories have been postulated to explain obesity-associated cardiac anomalies, including alterations in myocardial substrate utilization, neurohumoral activation, mitochondrial dysfunction, oxidative stress, impaired insulin signaling, and lipotoxicity, the underlying pathological mechanisms remain elusive (7). Obesity is known to trigger a number of adverse cellular signaling processes in the heart, such as re-expression of fetal genes, intracellular Ca²⁺ mishandling, derangement in proteins responsible for excitation-contraction coupling, and cardiac fatty acid oxidation (8,9). Obesity also triggers changes in extracellular matrix (10) and apoptosis of cardiomyocytes (11), which also can contribute to heart failure.Cathepsins are cysteine proteases that are ubiquitously expressed in various tissues and are implicated in the pathogenesis of cardiovascular diseases (12–14). Primarily located in lysosomes, cathepsins are transported between different cellular organelles and are released into the circulation under pathological conditions such as diabetes and atherosclerosis (15,16) or after lysosomal leakage caused by reactive oxygen species. Once released from lysosomes, cathepsins trigger apoptotic cell death by activating caspases and releasing proapoptotic factors from the mitochondria (17). Elevated levels of cathepsins S and K have been reported in atherosclerotic plaques, neointimal lesions, and in the failing heart in both humans and animals (18–21). Elevated levels of myocardial cathepsin B has been reported in individuals with dilated cardiomyopathy (22). However, deficiency of cathepsin L has been associated with cardiomyopathy whereas overexpression of this protease was shown to retard cardiac hypertrophy (23), suggesting distinct regulation of cardiac tissue by various cathepsins. Recent studies have shown that cathepsin K is elevated in adipose tissues of obese humans and mice and inhibition of cathepsin K attenuated body weight gain and serum glucose and insulin levels in obese mice (24). Given that cardiac dysfunction is a major complication of obesity, this study was designed to test the hypothesis that ablation of cathepsin K protects against high-fat diet–induced cardiac dysfunction. Our studies reveal that deletion of cathepsin K attenuates obesity-associated cardiac hypertrophy and contractile dysfunctions.     

Evaluation of renal biopsies in type 2 diabetic patients with kidney disease: a clinicopathological study of 216 cases

Objectives

The outcome and the therapy of patients with diabetes mellitus (DM), diabetic nephropathy (DN), and non-diabetic renal disease (NDRD) are quite different, so the differential diagnosis is of considerable importance. To evaluate the usefulness of renal biopsy in type 2 diabetic patients, we examined the relationship between the clinical parameters and the histopathological findings in different age groups.

Methods

Renal biopsy specimens and clinical and laboratory data from 216 patients with type 2 DM were evaluated. According to their age, three groups were defined: 17–35 years (group I), 36–59 years (group II), and more than 60 years (group III).

Results

The study showed that, beside the duration of diabetes, other clinical parameters were not significantly different between the three groups. Chronic nephritic syndrome was the most common clinical manifestation in group I (44.1 %) and in group II (34.0 %). Among patients in group III, we found a high prevalence of chronic renal failure (34.3 %) and nephrotic syndrome (28.6 %). Consistent with the clinical manifestations, IgA nephropathy was the most common pathologic finding in group I (29.4 %) and in group II (34.7 %), whereas the most frequent abnormalities in group III were membranous nephropathy (25.7 %) and tubulointerstitial lesions (14.3 %). Overall, among these patients, 14 cases were diagnosed with DN (6.5 %), 179 with NDRD (82.9 %), while 23 had concurrent DN and NDRD (10.7 %).

Conclusions

Our results indicated that the clinical manifestations and pathologic findings in type 2 diabetic patients in different age groups have different features. This study emphasized the usefulness of renal biopsy for determining the pattern of renal damage and thus for the overall management of type 2 diabetic patients.