The expression of Mirc1/Mir17–92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients

Introduction

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment.

Sleep and rest regulation in young and old oestrogen-deficient female mice

The effect of circulating oestrogen deficiency on sleep regulation and locomotor activity was investigated in aromatase cytochrome P450 deficient mice (ArKO) and wild-type (WT) controls. Sleep was recorded in 3-month old mice during a 24-h baseline day, 6-h sleep deprivation (SD) and 18-h recovery, and activity was recorded at the age of 3, 9 and 12 months. In mice deficient of oestrogen, the total amount of sleep per 24 h was the same as in WT controls. However, in ArKO mice, sleep was enhanced in the dark period at the expense of sleep in the light phase, and was more fragmented than sleep in WT mice. This redistribution of sleep resulted in a damped amplitude of slow-wave activity (SWA; power between 0.75-4.0 Hz) in non-rapid eye movement sleep across 24 h. After SD, the rebound of sleep and SWA was similar between the genotypes, suggesting that oestrogen deficiency does not affect the mechanisms maintaining the homeostatic balance between the amount of sleep and its intensity. Motor activity decreased with age in both genotypes and was lower in ArKO mice compared to WT at all three ages. After SD, the amount of rest in 3-month old WT mice increased above baseline and was more consolidated. Both effects were less pronounced in ArKO mice, reflecting the baseline differences between the genotypes. The results indicate that despite the pronounced redistribution of sleep and motor activity in oestrogen deficient mice, the basic homeostatic mechanisms of sleep regulation in ArKO mice remain intact.     

Cognition in the early stage of multiple sclerosis

Objective Cognitive dysfunctions may contribute to limitation of everyday activities of patients with multiple sclerosis (MS). Recent studies have demonstrated that 45 to 65% of MS-patients are cognitively impaired. The profile of MS-related cognitive dysfunctions varies greatly. It includes memory and learning deficits, attention deficits, executive dysfunctions and visuo-spatial deficits. Most studies of cognition in MS examined patients in later stages, often including MS-patients with marked physical disabilities. Studies of cognitive dysfunctions in the early stage of the disease are rare. This study specifically aimed at evaluating and characterizing cognitive impairments in the early stage of MS, and determining specific patterns of cognitive dysfunction. Methods 21 MS patients, experiencing their first neurological symptoms not more than two years previously, and 22 healthy controls were compared. A comprehensive neuropsychological test-battery was used to evaluate MS-related cognition. The battery consisted of memory and learning tests, executive functioning tests and a visuo spatial functioning test. A computerized attention test-battery was also included, which assess accuracy and speed of test responses. In addition depression and intellectual capabilities were assessed. Results Compared with healthy controls, MS-patients in the early stage of the disease performed significantly lower on each neuropsychological assessment, except for verbal short-term memory. In particular, MS-patients showed a lengthened reaction time for simple and focused attention (19–38%), impaired non-verbal memory function (RVDLT recognition: 33%) and a planning deficit (24%). Associations between information processing speed and disease course and the employment situation were additionally found. However, patients did not have clinically relevant depression rates on the ADS-L and visuo spatial abilities remain preserved. Conclusion Our findings revealed discrete cognitive dysfunction in MS-patients within the early stage of the disease. Received in revised form: 18 January 2006     

Quantitative study of spongiform change in putamen of 24 cases of Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is characterized by 4 main neuropathological lesions: spongiform change, neuronal loss, astrocytic gliosis, and accumulation of pathological prion protein (PrPsc), which is partially protease-resistant (PrPres). This study focused on spongiform change (SC) in the putamen. Because SC varies from case to case, we investigated whether its quantification could provide relevant criteria to discriminate types of PrPres in CJD. SC was quantified in 24 CJD cases, 12 with PrPres type 1 (CJD-PrP1) and 12 with PrPres type 2 (CJD-PrP2), compared to 25 control cases. The study was performed by direct microscopy examination (DME) and by semiautomatic quantification (SAQ) using shape and size criteria previously described. These criteria were suitable for SC quantification in putamen in the majority of cases, except for those with microspongiosis. The results obtained by DME and SAQ methods were correlated and SC scores were compared to the types of PrPres. Sporadic CJD cases with PrPres type 2 were more affected by SC than type 1, suggesting that putamen could be a preferential site to distinguish type 1 from type 2 histologically. The origin of the difference in SC intensity according to the type of PrPres is discussed in terms of host and strain factors.     

Comparison of implant survival with implants placed in acceptable and compromised bone: a literature review

Background  Survival rates for conventional dental implant systems are relatively high in normal healthy bone. However, there are subgroups of patients that are at an increased risk of implant failure. In particular, patients with compromised quantity or quality of bone present a significant challenge to the dental implantologist. Objective  To perform a review of the literature in an attempt to quantify the relative risk of implant failure in compromised bone compared to good or acceptable bone and to identify whether certain anatomical regions are at greater risk. Search Strategy  We conducted a systematic electronic database search of Medline, Cinhahl and the Cochrane Library through March 2006 identifying articles meeting the eligibility criteria. Results  We calculated an increased risk of implant failure in compromised bone compared to healthy bone in both the maxilla and the mandible using conventional dental implant systems. Relative risks ranged from 2 to 12 with the highest risk of failure in the maxilla. Conventional systems are often used in combination or after bone augmentation procedures or more innovative methods for stimulating bone growth in patients with compromised bone. These approaches do have their limitations including high costs, the accumulation of the surgical risks, and delayed time to loading. Discussion  Quantifying the risk of implant failure in patients with compromised bone should assist the implantologist in treatment decision making and patient counseling. Alternative methods for treating patients with compromised bone include zygomatic and lateral implants, neither of which typically require bone augmentation procedures. More studies are needed to evaluate their safety and efficacy.     

血浆置换显示干细胞移植后环孢素A引起的微血管病溶血性贫血和利福平的相应颜色反应

患者为1例39岁女性,患T/NK细胞淋巴瘤,在外周血异基因干细胞移植后15天,发生环孢素A(CSA)毒性相关的微血管病溶血性贫血(MAHA).因血清肌酐从移植前的0.4mg/dL,上升至移植后第9和15天的1.0和2.9 mg/dL.故停用CSA.     

人尿中几种雄激素及蛋白同化激素的HPLC测定

对HPLC分离及定量测定人尿中雄激素及蛋白同化激素的方法进行了初步研究。确定了六种甾体激素的分离条件及内标定量方法。固定相为C₈键合硅胶,甲醇—乙腈—水(4:5:6)恒溶剂洗脱,程序流速。紫外检测器波长254 nm。检测限可至1 ng以下。本法采用Sep-Pak C₁₈小柱进行尿样净化,回收率高而且稳定。操作简便快速。对尿样中甾体葡萄糖醛酸甙结合物的酶促水解条件也进行了初步探索。