Cell-to-cell contact of human monocytes with infected arterial smooth-muscle cells enhances growth of Chlamydia pneumoniae

Chlamydia pneumoniae can infect arterial cells. It has been shown that coculture of human monocytes (U937) and endothelial cells promotes infection of C. pneumoniae in endothelial cells and that the enhancement was mediated by a soluble factor (insulin-like growth factor 2) secreted by monocytes. In this study, it is shown that coculture of monocytes with C. pneumoniae enhances infection of C. pneumoniae in arterial smooth-muscle cells 5.3-fold at a monocyte-to-smooth-muscle cell ratio of 5. However, unlike endothelial cells, no enhancement was observed if monocytes were placed in cell culture inserts or if conditioned medium from monocyte cultures was used, which suggests that cell-to-cell contact is critical. The addition of mannose 6-phosphate or octyl glucoside, a nonionic detergent containing a sugar group, to cocultures inhibited the enhancement. These findings suggest that the monocyte-smooth-muscle cell interaction may be mediated by mannose 6-phosphate receptors present on monocytes.     

High Reported Treatment Satisfaction in People With Type 1 Diabetes Switching to Latest Generation Insulin Pump Regardless of Previous Therapy

Background:

The effects of transition by individuals with type 1 diabetes (T1D) to more recently available continuous glucose monitoring (CGM)-enabled insulin pumps from either multiple daily insulin injections (MDI) or older insulin pumps on treatment satisfaction have not been well studied. We conducted a survey to assess treatment satisfaction among users of the Animas^® Vibe™ insulin pump, a latest generation insulin pump (LGIP) system (CGM-enabled), after switching from MDI or earlier generation insulin pumps.

Methods:

Individuals with T1D from 141 centers in 5 countries and 4 language areas participated in the survey. Treatment satisfaction was assessed by the Insulin Treatment Satisfaction Questionnaire (ITSQ), which was included in a 50-item online questionnaire that also assessed preference for using the LGIP compared with previous treatment and satisfaction with key LGIP features.

Results:

A total of 356 individuals, ages 12-79 years, responded to the survey: mean (SD) age 38.4 (16.1) years; diabetes duration 19.1 (13.3) years; female 59%; previously treated with MDI 58%. Overall mean (SD) ITSQ scores were high among all respondents regardless of prior treatment: 95.1 (23.2) (scale: 0-132). No differences between previous-treatment groups were seen. Most (83%) of respondents rated the LGIP to be better than their previous insulin delivery system: “much better” (65%), “a bit better” (18%) regardless of age, and 95% would recommend using the LGIP to others.

Conclusions:

Use of the Animas Vibe was associated with high treatment satisfaction and perceived as a better method of insulin delivery regardless of previous insulin therapy or age.     

Unmet Physical Activity Need in Old Age

OBJECTIVES: To examine which individual and environmental factors correlate with unmet physical activity need in old age and predict development of unmet physical activity need (the feeling that one's level of physical activity is inadequate and thus distinct from the recommended amount of physical activity) over a 2‐year follow‐up. DESIGN: Observational prospective cohort study and cross‐sectional analyses. SETTING: Community and research center. PARTICIPANTS: A total of 643 community‐living ambulatory people aged 75 to 81 took part in face‐to‐face interviews and examinations at baseline and 314 at the 2‐year follow‐up. MEASUREMENTS: Unmet physical activity need and its potential individual and environmental correlates were assessed at baseline. Development of unmet physical activity need was assessed over the 2‐year follow‐up period. RESULTS: At baseline, all participants were able to walk at least 500 m outdoors, but 14% perceived unmet physical activity need. Unmet physical activity need was more prevalent in those with musculoskeletal diseases, depressive symptoms, and mobility limitations. Hills in the nearby environment, lack of resting places, and dangerous crossroads correlated with unmet physical activity need at baseline; the association was especially strong in those with walking difficulties. Significant baseline predictors for incident unmet physical activity need (15%) included fear of moving outdoors, hills in the nearby environment, and noisy traffic. CONCLUSION: Unmet physical activity need is common in ambulatory community‐living older people who have health and mobility problems and report negative environmental features in their neighborhood. Solutions to overcome barriers to physical activity need to be developed to promote equal opportunities for physical activity participation.     

Perioperative analgesia strategies in fast-track pediatric surgery of the kidney and renal pelvis: lessons learned

Purpose  

Effective analgesia is essential for the success of fast-track (FT) pediatric surgery. Aim of the study was to achieve an optimal analgesia protocol for a comfortable postoperative course and early mobilization in children undergoing urological procedures.     

Age and obesity-associated changes in the expression and activation of components of the AMPK signaling pathway in human right atrial tissue

Background

Obesity is associated with an increased incidence of left ventricular hypertrophy, diastolic dysfunction, heart failure, and premature cardiac aging. In the heart, intrinsic activation of the AMP-dependent protein kinase (AMPK) plays a pivotal role in the stress response to ischemia and hypertrophy. Furthermore, AMPK is an important regulator of cardiac mitochondrial biogenesis. The purpose of the present study was to investigate the influence of obesity and aging on the AMPK signaling pathway in human cardiac tissue.

Methods

60 male cardiac surgery patients were included in the study and divided into 4 groups (old normal weight: ON; old obese: OO; young normal weight: YN, young obese: YO) according to their body mass index (18.5–25: normal weight or 30–35: obese) and age (< 55 years: young or > 70: old) with 15 patients each. Right atrial tissue (RA) was analyzed for the expression of the AMPK upstream kinases CAMKK and LKB1, activation of AMPK as well as phosphorylation of the AMPK downstream targets ACC, eEF2, mTOR and eNOS. Epicardial adipose tissue was analyzed for the expression of the endogenous AMPK activator adiponectin. The metabolic state of all patients was further characterized in fasting blood samples.

Results

Old patients (ON, OO) and young obese (YO) subjects displayed higher fasting glucose, insulin and leptin serum levels compared to the young, normal weight group, although HbA1c was below the threshold required for the diagnosis of type 2 diabetes. Serum adiponectin as well as total adiponectin protein expression in epicardial adipose tissue was decreased in these three groups. Analyses of adiponectin isoforms by native gel electrophoresis revealed significant differences in the high molecular weight (HMW) isoforms between the groups. Despite the low total serum adiponectin and HMW adiponectin, AMPK activation was high in the RA of obese patients (YO, OO). Among the AMPK upstream kinases, LKB1 expression showed a strong positive correlation with AMPK activation. While the phosphorylation of the AMPK downstream targets mTOR, eEF-2 and ACC was not altered, phospho-eNOS was significantly lower in old patients (ON, OO). Despite strong AMPK activation, mitochondrial biogenesis and respiration were impaired in old (ON, OO) and young obese (YO) subjects.

Conclusion

These data indicate that obesity and aging result in significant changes although many direct parameters in the AMPK signaling pathway are not changed in the same direction. LKB1 may represent a stronger activator of the AMPK pathway than adiponectin or the CAMKKs in human right atrial tissue.     

Cell-polymer interactions of fluorescent polystyrene latex particles coated with thermosensitive poly(N-isopropylacrylamide) and poly(N-vinylcaprolactam) or grafted with poly(ethylene oxide)-macromonomer

Cell-polymer interactions of thermosensitive poly(N-isopropylacrylamide) (PNIPAM) or poly(N-vinylcaprolactam) (PVCL) coated particles with RAW264.7 macrophages and intestinal Caco-2 cells were evaluated. Nanosized particles were prepared by modifying the surface of fluorescent polystyrene (FPS) particles with the thermosensitive polymer gels or with poly(ethylene oxide) (PEO)-macromonomer grafts. The particles were characterized by IR-spectroscopy for functional groups, light scattering for size distribution and zeta-potential for surface charge. Effects of temperature and polymer coating/grafting on the cellular interactions were evaluated by cell association/uptake and visualized by confocal scanning microscope. PEO and PNIPAM inhibited the polymer-cell contact by steric repulsion, evidenced by weak attachment of the particles. PVCL-coated FPS was adsorbed on the cells more strongly, especially at 37 degrees C, because of more hydrophobic nature at higher temperatures. The results suggest feasibility of the PNIPAM and PVCL for biotechnological/pharmaceutical applications, as the cell-particle interactions may be modified by size, surface charge, hydrophobicity, steric repulsion and temperature.     

18q deletions: clinical, molecular, and brain MRI findings of 14 individuals

We studied 14 individuals with partial deletions of the long arm of chromosome 18, including terminal and interstitial de novo and inherited deletions. Study participants were examined clinically and by brain MRI. The size of the deletion was determined by segregation analysis using microsatellite markers. We observed that the phenotype was highly variable, even in two families with three 1st degree relatives. Among the 14 individuals, general intelligence varied from normal to severe mental retardation. The more common features of 18q-deletions (e.g., foot deformities, aural atresia, palatal abnormalities, dysmyelination, and nystagmus) were present in individuals lacking only the distal portion 18q22.3-qtel. Interstitial deletions exerted very heterogeneous effects on phenotype. In individuals with distal 18q22.3-q23 deletions, brain MRI was very distinctive with poor differentiation of gray and white matter on T2-weighted images.     

The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation,oxidative phosphorylation and ion homeostasis

The mechanisms of cell toxicity of mycotoxins of the enniatin family produced by Fusarium sp. enniatin B, a mixture of enniatin homologues (3% A, 20% A₁, 19% B, 54% B1) and beauvericin, were investigated. In isolated rat liver mitochondria, exposure to submicromolar concentrations of the enniatin mycotoxins depleted the mitochondrial transmembrane potential, uncoupled oxidative phosphorylation, induced mitochondrial swelling and decreased calcium retention capacity of the mitochondria. The mitochondrial effects were strongly connected with the potassium (K⁺) ionophoric activity of the enniatins. The observed enniatins induced K⁺ uptake by mitochondria. This shows that the enniatins acted as ionophores highly selective for potassium ions. The effects were observed in potassium containing media whereas less or no effect remained to be observed when K⁺ was partially or totally replaced by isomolar concentrations of Na⁺. The rank order of enniatin induced mitochondrial impairment was beauvericin > enniatin mixture > enniatin B. Exposure to the enniatins depleted the mitochondrial membrane potential also in intact human neural (Paju), murine insulinoma (Min-6) cells as well as boar spermatozoa. Exposure to enniatin B in media with physiological (4 mM) or low (<1 mM) but not in high (60 mM) external concentration of K⁺ induced hyperpolarization of the spermatozoal plasma membrane indicating enniatin that catalysed efflux of the cytosolic K⁺ ions. These results indicate that the cellular toxicity targets of the enniatin mycotoxins are the mitochondrion and the homeostasis of potassium ions.