Induction of blood-brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors

The blood-brain barrier (B-BB) protects the free passage of substances into the brain and maintains the homeostasis of the central nervous system. It is commonly accepted that astrocytes surrounding brain endothelial cells influence the B-BB formation and the exhibition of B-BB function of capillaries. To begin the in vitro study on the B-BB, it is essential to obtain a homogenous and sufficient supply of brain endothelial cells as well as astrocytes. We thus immortalized the bovine brain endothelial cell (BBEC) by transfection of the SV40 large T antigen and obtained a single clone, t-BBEC-117, which retained the brain endothelial cell phenotype. Astrocyte in co-culture was found to tighten the intercellular contacts of the immortal cells resulting in a reduced L-glucose permeability, and its conditioned medium (CM) augmented a B-BB phenotype, alkaline phosphatase (ALP) activity. Among known astrocytic factors, only fibroblast growth factor-basic (bFGF) could mimic the actions of astrocytes as measured by L-glucose permeability and ALP activity. Moreover, anti-bFGF antibody canceled 90% of ALP activation by astrocyte CM. Basic FGF, however, failed to induce other B-BB phenotypes such as the expressions of multidrug resistance (mdr) and glucose transporter (GLUT-1) genes. These data suggest that bFGF is one of the most plausible astrocytic factors to induce the B-BB properties of immortal brain endothelial cells together with some unknown factors in the astrocyte CM.     

Effects of 12 weeks of aerobic exercise plus dietary restriction on body composition,resting energy expenditure and aerobic fitness in mildly obese middle-aged women

This study investigated the effects of 12 weeks of aerobic exercise plus voluntary food restriction on the body composition, resting metabolic rate (RMR) and aerobic fitness of mildly obese middle-aged women. The subjects were randomly assigned to exercise/diet (n = 17) or control (n = 15) groups. The exercise/diet group participated in an aerobic training programme, 45–60 min · day ^–1 at 50%–60% of maximal oxygen uptake (VO_2max), 3–4 days · week^–1, and also adopted a self-regulated energy deficit relative to predicted energy requirements (–1.05 MJ · day ^–1 to –1.14 MJ · day ^–1 ). After the regimen had been followed for 12 weeks, the body mass of the subjects had decreased by an average of 4.5 kg, due mainly to fat loss, with little change of fat free mass (m _ff). The absolute RMR did not change, but the experimental group showed significant increases in the RMR per unit of body mass (10%) and the RMR per unit of m _ff (4%). The increase in RMR/m _ff was not correlated with any increase in VO_2max/m _ff. The resting heat production per unit of essential body mass increased by an average of 21%, but the resting heat production rate per unit of fat tissue mass remained unchanged. We concluded that aerobic exercise enhances the effect of moderate dietary restriction by augmenting the metabolic activity of lean tissue.     

Decreased cortical response to verbal working memory following sleep deprivation

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.     

A case of hyperlipoproteinemia caused by corticosteroid therapy in a child with subacute necrotizing lymphadenitis

A 10-year-old child was diagnosed as subacute necrotizing lymphadenitis. After a steroid hormone (predonine) administration for 17 days, he showed total cholesterol(TC) 420 mg/dl, triglyceride(TG) 839 mg/dl, and LDL-cholesterol 241 mg/dl. The hyperlipidemia seemed to be a side effect of the steroid at the onset. However, the lipoprotein fraction by the agarose gel and polyacrylamide gel (PAG) electrophoresis showed type III of the WHO classification, that is, presence of broad band as well as appearance of mid band, small dense-LDL and the disrupted type of LDL band. In addition, there were hyperlipidemia (high levels of the TC, TG, LDL-cholesterol) in 4 persons out of 6 family members, and LDL pattern of the PAG electrophoresis, 4 persons showed the nodular type. They have higher possibility of combined-type familial hyperlipiemia from the above results, and it seemed to be the case in which the hyperlipidemia was exacerbated by the steroid administration.     

Non-functional adrenocortical adenoma with extensive degeneration

We report a case of non-functional adrenocortical adenoma of 5.5 x 5.5 x 3.2 cm in size that had an unusual histopathological appearance in two respects. First, the tumor contained small adipose foci with osteogenesis and was suspected of being a myelolipoma based on its appearance on computerized tomography (CT) and magnetic resonance imaging. However, pathologically, the fat element was seen focally and was not accompanied by hematopoietic cells, and the diagnosis of myelolipoma was abandoned. Second, the tumor was suspected of being an adrenal carcinoma based on its appearance on CT scans and showed extensive degeneration: fibrosis, hemorrhage, loss of parenchyma and moderate atypism of the tumor cells. However, as the architecture of the tumor cells was non-diffuse and there were no necrotic foci or mitoses, and vascular or capsular invasion were not present, the tumor was concluded to be an adrenocortical adenoma rather than a carcinoma. We diagnosed the tumor as a non-functional adrenocortical adenoma with extensive degeneration as the extensive areas of fibrosis were particularly remarkable. Furthermore, the extensive areas of degeneration might have been caused not only by an ischemic effect but also by low hormone levels.     

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.     

Nutritional Assessment in Adult Patients with Dysphagia: A Scoping Review

Malnutrition negatively affects the quality of life of patients with dysphagia. Despite the need for nutritional status assessment in patients with dysphagia, standard, effective nutritional assessments are not yet available, and the identification of optimal nutritional assessment items for patients with dysphagia is inadequate. We conducted a scoping review of the use of nutritional assessment items in adult patients with oropharyngeal and esophageal dysphagia. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to identify articles published in English within the last 30 years. Twenty-two studies met the inclusion criteria. Seven nutritional assessment categories were identified: body mass index (BMI), nutritional screening tool, anthropometric measurements, body composition, dietary assessment, blood biomarkers, and other. BMI and albumin were more commonly assessed in adults. The Global Leadership Initiative on Malnutrition (GLIM), defining new diagnostic criteria for malnutrition, includes the categories of BMI, nutritional screening tool, anthropometric measurements, body composition, and dietary assessment as its required components, but not the blood biomarkers and the “other” categories. We recommend assessing nutritional status, including GLIM criteria, in adult patients with dysphagia. This would standardize nutritional assessments in patients with dysphagia and allow future global comparisons of the prevalence and outcomes of malnutrition, as well as of appropriate interventions.     

Association between Preoperative Long-Chain Polyunsaturated Fatty Acids and Oxidative Stress Immediately after Total Knee Arthroplasty: A Pilot Study

Quadriceps muscle atrophy following total knee arthroplasty (TKA) can be caused by tourniquet-induced ischemia–reperfusion (IR) injury, which is often accompanied by oxidative stress and inflammatory responses. n-3 long-chain polyunsaturated fatty acids (LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antioxidant and anti-inflammatory effects against IR injury, whereas n-6 LCPUFAs, particularly arachidonic acid (AA), exhibit pro-inflammatory effects and promote IR injury. This study aimed to examine whether preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio are associated with oxidative stress immediately after TKA. Fourteen eligible patients with knee osteoarthritis scheduled for unilateral TKA participated in this study. The levels of serum EPA, DHA, and AA were measured immediately before surgery. Derivatives of reactive oxygen metabolites (d-ROMs) were used as biomarkers for oxidative stress. The preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio were found to be significantly negatively correlated with the serum d-ROM levels at 96 h after surgery, and the rate of increase in serum d-ROM levels between baseline and 96 h postoperatively. This study suggested the preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio can be negatively associated with oxidative stress immediately after TKA.     

Ultrasound biomicroscopic analysis of the effect of pilocarpine on the anterior chamber angle

Background: This study was carried out to determine the effects of pilocarpine on the anterior chamber angle in healthy volunteers. Methods: We measured changes in anterior chamber depth (ACD), trabecular-iris angle (TIA), angle opening distance at 250 and 500 m from the scleral spur (AOD250 and AOD500), and iris thickness using ultrasound biomicroscopy in 48 eyes of 48 normal volunteers (ages 18–57 years, mean 34.8 years) before and 1 h after instillation of 2% pilocarpine. Results: Pilocarpine altered the TIA by –18.6° to + 10.5° (mean –4.16°), and change in the TIA increased significantly and linearly in relation with decrease in the pretreatment TIA (r = 0.929). Pilocarpine altered AOD250 change by –136 to +94 m (mean –38 m) and AOD500 by –151 to +157 m (mean –42 m); changes in the AOD250 and AOD500 were significantly correlated to the pretreatment AOD250 and AOD500 values, respectively (r = 0.923 andr = 0.896, respectively). The pilocarpine-induced change in the ACD showed a linear relationship to the pretreatment ACD (r = 0.887). The changes in the TIA, AOD250 and AOD500 showed greater increases in association with lower pretreatment ACD (r = 0.848,r = 0.891,r = 0.842) and smaller change in the ACD (r = 0.834,r = 0.839,r = 0.812). Conclusions: The response of the anterior chamber angle to pilocarpine, narrowing or widening, depended on its pretreatment state. The ability to predict the pilocarpine-induced change in the angle before the instillation of pilocarpine would be helpful in treating patients with glaucoma.