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Sham-operated Rabbits (sham-operated + rabbits)
Selected AbstractsFatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded heartsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2004T. Miyamoto Abstract Background, The peroxisome proliferator-activated receptor (PPAR) , is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPAR, and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. Methods, Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by ,-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPAR, and fatty acid oxidation enzymes were examined by Western blotting. Results, Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0·06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by ,-oxidation was faster than the sham-control hearts (P < 0·05). However, protein levels of PPAR, and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. Conclusions, These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPAR, and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli. [source] Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscleNEUROUROLOGY AND URODYNAMICS, Issue 1 2006Anita S. Mannikarottu Abstract Aims Obstruction of the urinary bladder outlet induces detrusor smooth muscle (DSM) hypertrophy. The goal of this study was to determine whether the composition of thin filament-associated proteins, known to play important roles in cytoskeletal structure and/or the regulation of contraction, is altered in DSM during hypertrophy. Methods DSM hypertrophy was induced in male rabbits by partial ligation of the urethra. Sham-operated rabbits served as a control. Reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR revealed a significant increase in the expression of mRNAs for basic (h1) calponin (CaP), and ,-isoform of tropomyosin (Tm) in hypertrophied DSM compared to controls. Western blotting and two-dimensional (2-D) gel electrophoresis showed enhanced expression of these proteins and also a significant increase in the expression of ,-non muscle and ,-smooth muscle actin in the DSM from obstructed bladders, while ,-actin remained constant. Results Enhanced expression of these proteins in the DSM from obstructed bladders was confirmed by immunofluorescence microscopy. Double immunostaining with Cap/Tm and ,/,-actin-specific antibodies showed co-localization of these proteins in myocytes. Colocalization of smooth muscle specific myosin and CaP to cytoplasmic filaments in cells dissociated from the hypertrophied DSM indicated that these cells are differentiated smooth muscle cells. Conclusions The change in the isoforms of actin, Cap, and Tm may be part of the molecular mechanism for bladder compensation in increased urethral resistance. Neurourol. Urodynam. © 2005 Wiley-Liss, Inc. [source] Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstructionNEUROUROLOGY AND URODYNAMICS, Issue 2 2006Edward LaBelle Abstract Aims Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. Methods Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits. Results The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 µM. Conclusions The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Eviprostat suppresses urinary oxidative stress in a rabbit model of partial bladder outlet obstruction and in patients with benign prostatic hyperplasiaPHYTOTHERAPY RESEARCH, Issue 2 2010Seiji Matsumoto Abstract Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity. The present study investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8-hydroxy-2,-deoxyguanosine (8-OHdG) in a rabbit model of surgical partial bladder outlet obstruction (PBOO) and in patients with lower urinary tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of sham-operated rabbits. When twice-daily Eviprostat was administered orally throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5-fold lower urinary 8-OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 ± 2.74 to 13.67 ± 2.30 and the quality of life score from 4.22 ± 0.40 to 3.22 ± 0.46. The findings provide evidence that the antioxidant activity of Eviprostat is responsible for its beneficial effects in the treatment of BPH. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||