Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy

Sleep and Breathing -     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis.

OBJECTIVES: To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. PATIENT AND METHODS: This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. RESULTS: Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. CONCLUSION: Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.

OBJECTIVE: The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. STUDY DESIGN: The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. RESULTS: After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. CONCLUSIONS: The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.     

嗅鞘细胞移植在大鼠脊髓损伤处能够迁移和促进神经轴突生长吗?

目的：探讨嗅鞘细胞（olfactory ensheathing cells,OEC）移植在大鼠损伤脊髓后是否有独特的迁移和轴突生长导向特性。方法：将表达绿色荧光蛋白基因的OEC注入到C4脊髓损伤大鼠距离损伤部位头端1mm及尾端1mm背柱白质处,注射后1、3、12、24h及3、7、28d灌注固定取材,冰冻切片和免疫组化分析。用骨髓基质细胞和成纤维细胞移植到同样的损伤部位做为对照进行同样的分析。另将OEC注射到距离损伤部位头尾侧1mm处脊髓灰质内、小剂量注射在白质内、在损伤前3d或损伤后9d注射、注射到未损伤脊髓白质中,观察细胞迁移情况。结果：OEC在细胞注射后1h内即形成由注射压力造成的从注射部位向损伤处的被动性延伸带,并且不断地从注射部位向损伤处延伸扩散,在形态学方面好象起到＂桥接＂损伤处的作用。对照组骨髓基质细胞和成纤维细胞注射后也迅速形成细胞＂桥接＂带,并扩散至损伤空腔。将OEC注射到脊髓灰质内或小剂量注射或注射到未损伤的脊髓白质内、在脊髓损伤3d前或9d后注射细胞均没有见到细胞带延伸进入损伤部位。OEC在注射部位、细胞带以及损伤部位有增殖现象。28d后,共焦免疫酶标法证实细胞带取代了脊髓原有星形胶质细胞,但是下行或上行长束轴突没有优先延伸至该细胞带,也没能起到维持皮层脊髓轴突的桥接作用。结论：OEC在植入大鼠损伤脊髓后没有独特的迁移特性,与骨髓基质细胞或成纤维细胞相比没有明显促进轴突生长的作用,也没有支持皮层脊髓轴突在脊髓损伤处形成桥接的作用。     

Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.

BACKGROUND: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis. AIMS/METHODS: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss). RESULTS: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome. CONCLUSION: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.     

Systematic and random errors in compression testing of trabecular bone

We sought to quantify the systematic and random errors associated with-artifacts in the platens compression test for trabecular bone. Our hypothesis was that while errors may depend on anatomic site, they do not depend on apparent density and therefore have substantial random components. Trabecular bone specimens were first tested nondestructively using newly developed accurate protocols and then were tested again using the platens compression test. Percentage differences in modulus between the techniques (bovine) proximal tibia [n = 18] and humerus [n = 17] and human lumbar spine, [n = 9] were in the range of 4-86%. These differences did not depend on anatomic site (p = 0.21) and were only weakly dependent on apparent density and specimen aspect ratio (r² < 0.10). The mean percentage difference in modulus was 32.6% representing the systematic component of the end-artifact error. Neglecting the minor variations explained by density and specimen size (approximately 10%), an upper bound on the random error from end-artifacts in this experiment was taken as the SD of the modulus difference (±18.2%). Based on a synthesis of data taken from this study and from the literature, we concluded that the systematic underestimation error in the platens compression test can be only approximated and is in the range of 20-40%; the substantial random error (±12.5%) confounds correction, particularly when the sample size is small. These errors should be considered when interpreting results from the platens test, and more accurate testing techniques should be used when such errors are not acceptable.     

Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.