Ceramides are associated with inflammatory processes in human mediastinal adipose tissue

Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles.Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m²). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism.ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.     

Subclinical albuminuria is linked to gray matter atrophy in type 2 diabetes mellitus

Objective

Microalbuminuria (MA), a marker of renal microvascular disease, is associated with brain atrophy and neurovascular changes in older adults with type 2 diabetes mellitus (DM). We evaluated the relationship between urine albumin-to-creatinine ratio (UACR) and regional brain volumes to determine whether subclinical albuminuria may indicate early structural brain changes in type 2 DM.

Materials/Methods

We studied UACR and brain volumes in 85 type 2 DM patients (64.8 ± 8.3 years) and 40 age-matched controls using 3D magnetization prepared rapid acquisition with gradient echo (MP-RAGE) MRI (magnetic resonance imaging) at 3 Tesla. The relationship between UACR and brain volumes was analyzed using the least square models.

Results

In DM patients, UACR ≥ 5 mg/g, UACR ≥ 10 mg/g and clinically significant MA (UACR ≥ 17 mg/g [males] and 25 mg/g [females]) were associated with lower gray matter (GM) volume in the frontal lobe (r²_adj = 0.2–0.4, P = 0.01–0.05) and UACR ≥ 5 mg/g was also related to global GM atrophy (r²_adj = 0.1, P = 0.04), independent of DM duration, glucose levels, HbA_1c and hypertension. For UACR ≥ 5 mg/g, a lower global GM volume was related to worse executive function (P = 0.04) in the DM group. No associations were found for UACR (< 5 mg/g) and controls.

Conclusions

Subclinical albuminuria (UACR ≥ 5 mg/g) is associated with lower GM volume that has clinical impact on cognitive function in older diabetic patients, and these relationships are independent of DM control and hypertension. Therefore, UACR levels may serve as an additional marker of DM-related brain structural changes.     

Age-associated changes of cerebrospinal fluid amyloid-β and tau in cynomolgus monkeys

Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop β-amyloid (Aβ) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associated changes in Aβ and tau protein in cerebrospinal fluid. The present study was an attempt to specifically address these issues. Cerebrospinal fluid levels of Aβ and phosphorylated tau were measured in 37 and 22 cynomolgus monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from the present study revealed significant age-associated declines in Aβ42 levels but not in Aβ40 and phosphorylated tau levels. This finding appears to parallel changes seen with human aging, in which decreased levels of Aβ42 can be seen in normal older adults, and supporting that cynomolgus monkeys would be a useful model for studying age-related neurologic disorders associated with Alzheimer-like cerebral proteopathy.     

The role of aquaporin-1 in idiopathic and drug-induced intracranial hypertension

Idiopathic intracranial hypertension is a common disorder affecting mainly healthy, young, overweight women. The pathogenesis of this condition is unknown, but it has been shown to follow treatment with several compounds including corticosteroids and vitamin A derivatives. This paper will offer a novel hypothesis and insight on the pathogenesis of drug induced intracranial hypertension following a review and analysis of the literature. Both corticosteroids and vitamin A derivatives have been shown to upregulate the expression of aquaporin 1, a water channel protein. Aquaporin 1 is widely distributed in the human brain and is associated with water secretion into the subarachnoid space. Aquaporin 1 was also shown to participate in the regulation of weight. Agents used for treating idiopathic intracranial hypertension reduce aquaporin 1 expression. Based on these observations, we propose that aquaporin 1 has a pathogenetic role in drug induced idiopathic intracranial hypertension. Over expression of this gene causes increased intracranial pressure, and downregulation reduces pressure and alleviates the symptomatology and complications of idiopathic intracranial hypertension.     

微生物检验在肺曲霉菌感染患者临床诊治中的应用价值

目的分析微生物检验在肺曲霉菌感染临床诊断及治疗中的应用价值。方法回顾性选择2017年8月至2019年9月接收的75例肺曲霉菌感染患者为研究对象,采用GM试验、G试验及痰培养三种方法予以微生物检验,比较三种检测方法及联合检验对肺曲霉菌的阳性检出率。同时,比较寄生型和侵袭型肺曲霉菌感染患者的临床表现、治疗方法及预后。结果GM试验对寄生型、侵袭型肺曲霉菌的阳性检出率均高于G试验和痰培养(P<0.05);三项联合检验对寄生型肺曲霉菌的阳性检出率均高于三项单独检验(P<0.05);三项联合检验对侵袭型肺曲霉菌的阳性检出率均高于G试验和痰培养单独检验(P<0.05)。寄生型肺曲霉菌感染患者咯血发生率高于侵袭型肺曲霉菌感染患者,发热、咳嗽、胸闷及肺啰音发生率均低于侵袭型肺曲霉菌感染患者(P<0.05)。寄生型肺曲霉菌感染患者以手术治疗为主,药物治疗为辅,治愈率为94.00%;侵袭型肺曲霉菌感染患者以药物治疗为主,治愈率为92.00%。结论微生物检验方法的联合应用可有效提高肺曲霉菌感染的诊断率,并为寄生型和侵袭型肺曲霉菌感染患者的治疗方法及预后评估提供参考依据。