Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice

Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice.     

Opsoclonus-myoclonus syndrome following long-term use of cyclosporine

Background: Cyclosporine A (CsA) is a widely used immunosuppressive agent that may provoke unexpected neurologic complications. The mechanism is unclear and variable intervals have been reported between CsA administration and onset of the related side effects. Here, we describe a case of delayed-onset CsA neurotoxicity presenting as opsoclonus-myoclonus syndrome (OMS).

Case details: A 37-year-old woman with a two-week period of opsoclonus and upper extremity myoclonus was admitted to our hospital. The patient had been taking CsA for 17 years after receiving a kidney transplant. Further evaluation did not reveal any other abnormalities. Seven days after switching from CsA to tacrolimus, in the absence of additional immune-modulating therapy, her neurologic symptoms improved considerably.

Conclusion: This is the case of delayed, long-term complications of CsA presenting as OMS. Symptoms resolved by substituting CsA with another immunomodulating drug. The etiology of the neurologic complications may involve paradoxically-enhanced delayed-type hypersensitivity.     

Effect of preload on left ventricular longitudinal strain by 2D speckle tracking

Background: Peak systolic longitudinal strain (PSLS) obtained using the 2D speckle tracking method is a novel indicator of the long‐axis function of the left ventricle (LV). We used the 2D strain profile to examine the effect of preload reduction by hemodialysis (HD) on LV PSLS in patients with end‐stage renal disease (ESRD). Method and results: Twenty‐nine pairs of echocardiographic evaluations were obtained before and after dialysis. Global LV PSLS was ?18.4 ± 2.9%, at baseline and decreased to ?16.9 ± 3.2% after HD (P < 0.001). Segmental analysis showed that the decrease in PSLS after dialysis was most prominent in mid‐LV segments (?17.1 ± 3.5% vs. ?15.4 ± 3.4%, P < 0.001). Conclusion: PSLS obtained from the 2D strain profile is a reliable parameter that may be useful for evaluating LV systolic long‐axis function. However, PSLS should be applied cautiously in ESRD patients because it could be affected by dialysis.     

Angiographic branching patterns of the splenic artery

Most previous studies of the splenic artery were cadaver dissections, andin vivo anatomical studies have been reported only rarely. Selective arteriography could be used as anin vivo study of the branching patterns of the splenic artery. Forty-three splenic arteriograms and seven celiac arteriograms were included in this study. There were 36 males and 14 females, aged 23–67 years (mean 48 years). The branching patterns of the splenic artery show 80% dorsal pancreatic, 98% pancreatic magna, 84% caudal pancreatic, 76% superior polar, 24% inferior polar, 46% left gastroepiploic, 28% accessory left gastric, 100% terminal superior and inferior, and 28% terminal media arteries. The branching patterns of the splenic artery were similar to the many reports of cadaver dissection in the Korean literature and there was a more frequent incidence of splenic arterial branches than in the reports from the study of Caucasians except for the accessory left gastric artery.     

Telomerase activity in acute myelogenous leukaemia: clinical and biological implications

We examined telomerase activity in myeloid leukaemic cell lines, normal haemopoietic cells, and leukaemic blasts from acute myelogenous leukaemia (AML) patients. Normal bone marrow mononuclear (BMNC) cells expressed low telomerase activity. Higher telomerase activity was detected in 10 myeloid leukaemic cell lines compared to normal BMNC cells. Treatment with 1,25(OH)₂D₃, and vitamin D₃ analogues, EB1089 and KH1060, reduced telomerase activity in vitamin D₃-sensitive HL-60 cells, whereas vitamin D₃ insensitive K562 cells did not change its activity. This down-regulation of telomerase activity by EB1089 was associated with induction of p21 protein. The rank order of telomerase activity was leukaemic CD34⁻ cells > leukaemic CD34⁺ cells > normal CD34⁻ cells > normal CD34⁺ cells. Telomerase activity was positive in all of the AML patients tested; however, heterogeneity of telomerase activity was found amongst this group. Therefore we compared telomerase activity with clinical response. Unexpectedly, we found that a higher rate of complete remission was noted in AML patients with higher telomerase activity. No association between telomerase activity and biological parameters including percentage of S-phase, cytotoxicity to cytosine arabinoside and percentage of CD34⁺ cells in AML blasts was found. These results suggest that telomerase activity in AML patients is detected with high frequency, but is heterogenous. Expression level of telomerase activity may have a clinical implication in AML patients regarding clinical response.     

Preload dependency of the time interval between the onset of mitral inflow and the early diastolic annular motion: a hemodialysis-related preload reduction study.

BACKGROUND: The novel parameter T(E-E'), which is the time interval between the onset of the early diastolic mitral inflow velocity (E) and the early diastolic mitral annular velocity (E'), is reported to be related to the constant of the left ventricular (LV) relaxation, and T(E-E') is also reported to be useful for predicting the LV filling pressure. METHODS AND RESULTS: To investigate the effect of preload reduction via hemodialysis on T(E-E'), 28 pairs of echocardiographic evaluations were performed just before and immediately after hemodialysis, including the measurement of the T(E-E') as well as measurement of the conventional echocardiographic parameters. The baseline T(E-E') was 17.9 +/-28.1 ms, which correlated with the ratio of E/E' (r=0.49, p=0.008). After hemodialysis, T(E-E') was shortened to -3.2+/-34.1 ms, which was a significant change from baseline (p=0.001). CONCLUSIONS: As T(E-E') is a preload dependent parameter, the intravascular volume status should be taken into account when the clinical application of T(E-E') is considered as an index of LV relaxation.     

Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty

Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6 × 6 cm²) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded nonsurgical control gains (144%) encountered due to animal growth. Similarly, elevations in bladder compliance were substantially higher in augmented animals from baseline (Group 1: 357%; Group 2: 147%) in comparison to controls (41%). Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair.