Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury

IntroductionPreservation of the cavernous nerves (CNs) during radical prostatectomy is crucial for the patient's erectile function. Despite advances in operative technique, the majority of men report compromised erectile function postprostatectomy or complete loss of potency due to CN trauma even with nerve-sparing modifications.AimThis study was designed to investigate whether repeated dosing of udenafil, a phosphodiesterase type 5 inhibitor, helps to improve erectile function after CN injury.MethodsUsing the CN crush injury model, 8-week-old male Sprague Dawley rats were divided into the following groups; sham-operated group, bilateral CN crush injury exposed to either no udenafil (vehicle) or udenafil (5, 20 mg/kg) daily for two different durations (4 and 8 weeks, p.o.).Main Outcome MeasuresAt both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expressions of hypoxia-inducible factor 1-alpha (HIF-1α), transforming growth factor-beta (TGF-β1), nerve growth factor (NGF), endothelin B receptor (ET_B), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sonic hedgehog homolog (SHH) in penile tissue were examined. Immunohistochemical antibody staining was performed for NGF, eNOS, nNOS, CD31, and alpha-smooth muscle actin (α-SMA). Additionally, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay was performed to quantify apoptosis and the tissue slides were stained for Masson's trichrome to assess the smooth muscle/collagen ratio.ResultsUdenafil improved erectile function in a dose- and time-dependent manner with the maximum erectile function recovery achieved by 20 mg/kg udenafil at an 8-week time point. CN injury increased the expression of HIF-1α, TGF-β1, NGF, and ET_B, however, decreased the expression of eNOS, nNOS, and SHH. Udenafil significantly suppressed these alterations. The results from the histological analyses show that udenafil markedly reduces apoptosis induced by CN injury and augments the smooth muscle/collagen ratio.ConclusionsCN injury induces significantly impaired erectile function and altered gene/protein expression. Chronic administration of udenafil preserves erectile function and has a beneficial role against the pathophysiological consequences of CN injury. Lee C-H, Kim H-S, Goo M-J, Kang K-K, Ahn B-O, Kim SH, and Yang D-Y. Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury.     

Optimization of ventricular catheter placement via posterior approaches: a virtual reality simulation study

BACKGROUND: This study aimed to evaluate 2 commonly used posterior approach entry points for ventricular cannulation and the ideal trajectories using 3-dimensional virtual reality technology. METHODS: Magnetic resonance imaging data of 10 patients without gross ventricular dilatation or distortion were retrieved and reconstructed. A stereoscopic 3-dimensional preoperative planning system was used to designate the entry points. Various trajectories were simulated. The ideal trajectory was determined as the one that provided direct entry into the atrium or body of the lateral ventricle en route to the ipsilateral frontal horn. RESULTS: Magnetic resonance imaging data sets from 10 patients were used. For the entry point 6 cm above and 4 cm lateral to the inion (Frazier's point), ideal cannulation was achieved for all 10 patients when the selected target was 4 cm above the contralateral medial canthus. When the contralateral medial canthus was targeted, 5 patients had successful outcomes. There were only 3 satisfactory outcomes each when the ipsilateral medial canthus and glabella were targeted. The target 2 cm above the glabella yielded 2 satisfactory outcomes. The entry point 3 cm above and 2 cm lateral to the inion (Dandy's point) had 10 satisfactory outcomes when the target point was 2 cm above the glabella. All the other target points, namely, ipsilateral medial canthus, contralateral medial canthus, 4 cm above the contralateral medial canthus and glabella yielded poor results. CONCLUSIONS: For satisfactory placement when entering via Frazier's point, the best trajectory target would be 4 cm above the contralateral medial canthus. When entering via Dandy's point, the best target would be 2 cm above the glabella.     

Renoprotective and antioxidant effects of Saururus chinensis Baill in rats fed a high-fructose diet

This study investigated the preventive effect of Saururus chinensis Baill against renal damage induced by a high-fructose diet in rats. The rats (n = 30) were fed either a cornstarch-based (65%), high-fructose (65%), or high-fructose (64.5%) diet with 0.5% S. chinensis Baill extract for 10 weeks. Twenty-four hour urine collections were obtained and the animals were sacrificed after an overnight fast. Serum urea and creatinine and urine albumin were measured using colorimetric methods, and creatinine clearance was determined. In addition, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and the activity of superoxide dismutase (SOD) in the kidney were determined. Kidney samples were also examined histologically. The fructose-fed rats showed renal dysfunction, indicated by decreased creatinine clearance, increased albumin in the urine, and increased urea and creatinine in the serum. These renal function parameters were comparable to control levels in rats that consumed S. chinensis Baill. Fructose consumption increased renal TBARS and reduced GSH and SOD activity, whereas these levels were near-normal in the rats consuming S. chinensis Baill. The kidneys of fructose-fed rats showed glomerular basement membrane thickening, mesangial matrix expansion, and tubule dilation. These pathological changes were not seen in the rats that consumed S. chinensis Baill. Therefore, S. chinensis Baill effectively alleviated fructose-induced renal damage in these rats, at least partially due to antioxidant activity.     

Recent advances in diagnosis and treatment for patients with vertigo

The number of patients who suffer from vertigo or dizziness becomes greater during the sixth and seventh decades of life and is now increasing to total, which could be related to recent longer life expectancy. Pertinent medical care should be given to those patients to better obtain so-called quality of life (QOL), and this could be attained with the help of accurate diagnosis. In general,accurate diagnosis is made by thorough neurotological examinations.     

N‐glycosylation status of β‐haptoglobin in sera of patients with colon cancer,chronic inflammatory diseases and normal subjects

N‐glycosylation status of purified β‐haptoglobin from sera of 17 patients, and from sera of 14 healthy volunteer subjects, was compared by blotting with various lectins and antibodies. Patients in this study were diagnosed as having colon cancer through histological examination of each tumor tissue by biopsy. Blotting index of serum β‐haptoglobin with Aleuria aurantia lectin (AAL) was clearly higher for cancer patients than for healthy subjects. No such distinction was observed for blotting with three other lectins and two monoclonal antibodies. To determine tumor‐associated reactivity of AAL binding as compared to inflammatory processes in colonic tissues, β‐haptoglobin separated from sera of 5 patients with Crohn's disease (CD), and 4 patients with ulcerative colitis (UC), was studied. All these cases, except one case of UC, showed AAL index lower than that in cancer cases, similarly to healthy subjects. The higher AAL binding of β‐haptoglobin in colon cancer patients than in healthy subjects appeared to be due to α‐L‐fucosyl residue, since it was eliminated by bovine kidney α‐fucosidase treatment. N‐linked glycans of serum haptoglobin from colon cancer patients vs. healthy subjects were released by N‐glycanase, fluorescence‐labeled, and subjected to normal‐phase high performance liquid chromatography (NP‐HPLC). Glycan structures were determined based on glucose unit (GU) values and their changes upon sequential treatment with various exoglycosidases. Glycosyl sequences and their branching status of glycans from 14 cases of serum β‐haptoglobin were characterized. The identified glycans were sialylated or nonsialylated, bi‐antennary or tri‐antennary structures, with or without terminal fucosylation.     

Association of apolipoprotein J-positive β-amyloid plaques with dystrophic neurites in alzheimer’s disease brain

Apolipoprotein J (apoJ), also known as clusterin and SP-40,40, binds soluble beta-amyloid (Aβ and is up-regulated in the Alzheimer’s disease (AD) brain. In the present study we classified apoJ-immunopositive Aβ deposits in AD temporal cortex, and found apoJ-immunoreactive plaques were often associated with dystrophic neurites. Quantitative immunohistochemical analysis of five AD brains showed that 29% of Aβ deposited in the parenchyma was associated with apoJ. Of Aβ deposits with apoJ immunopositivity, 71% were associated with phospho-tau-positive dystrophic neurites in the surrounding tissue. Conversely, 64% of phospho-tau-labeled neuritic deposits were labeled with apoJ. ApoJ was found at the core of these deposits, and co-localized with the amyloid staining agent thioflavine-S. To test the direct effects of apoJ on tau metabolism, we treated cells in culture with apoJ-containing conditioned media, and we injected apoJ-containing media into the rat hippocampus. Using both systems, we observed increases in levels of tau and phosphorylated tau. Our findings demonstrate that apoJ immunopositivity strongly correlates with the presence of amyloid and associated neuritic dystrophy in the neuropil of AD temporal cortex, and supports a model where extracellular apoJ facilitates the conversion of diffuse Aβ deposits into amyloid and enhances tau phosphorylation in neurites surrounding these plaques.     

Estrogen release from metallic stent surface for the prevention of restenosis.

For the prevention of coronary restenosis, estrogen was coupled onto a metallic stent and in vitro release of estrogen was investigated. Estrogen was introduced to the metal surface using a hydrolysable covalent bond for local sustained delivery of drug as follows: (i) the stainless steel (SS) surface was activated with silane by plasma polymerization, (ii) the activated surface (SS-Si surface) was treated with acrylic acid by plasma polymerization (SS-Si-AAc surface), and (iii) 17beta-estradiol (E2) was covalently linked to the carboxyl group on that surface (SS-Si-AAc-E2 surface). The modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, and water contact angle measurement. The amount of E2 was measured by UV-visible spectrophotometry and high performance liquid chromatography (HPLC). The in vitro release profile of E2 demonstrated sustained release of E2 in aqueous buffer. In summary, a novel method of immobilizing estrogen onto a metallic stent surface using plasma polymerization has been developed. The obtained results attest to the usefulness of the estrogen-releasing stent for preventing restenosis.     

Potential role of Ca++ on the differentiation of erythroid progenitor cells

In order to gain insight into the mechanisms by which erythropoietin promotes erythropoiesis, effects of various inhibitors on the erythropoietin-promoted differentiation of erythroid progenitor cells and on the erythropoietin-promoted Ca⁺⁺ uptake in the progenitor cells were determined, and the relationship between the inhibitory activity of each inhibitor toward the differentiation and Ca⁺⁺ uptake were examined. The inhibitors used were a tyrosine kinase inhibitor (genistein), a Ca⁺⁺-channel blocker (verapamil), a Ca⁺⁺ chelator (EDTA) and a protein kinase C inhibitor (staurosporine). All of these agents inhibited both the erythropoietin-mediated differentiation of the erythroid progenitor cells, as determined by the incorporation of⁵⁹Fe into heme, and Ca⁺⁺ uptake in a concentration dependent manner. In the cases of verapamil and EDTA, the half-miximal inhibitory concentration (IC₅₀) values for differentiation of the progenitor cells may be the consequence of the inhibition of the Ca⁺⁺ uptake by the inhibitior. On the other hand, in the cases of genistein and staurosporine, the IC₅₀ values for inhibition of differentiation were significantly different from that for inhibition of Ca⁺⁺ uptake. These results suggest that the mechanism of inhibition of differentiation by these two inhibitors is complex. However, taken all together, the above results support the proposition that Ca⁺⁺ uptake may paly a role in the erythropoietin-mediated differentiation of erythoid progenitor cells.     

Validation of a driving simulator by measuring the visual attention skill of older adult drivers.

OBJECTIVE: The purpose of this study was to validate a laboratory-based driving simulator as an off-road screening tool for older adult drivers by measuring their visual attention skill, and to determine how the visual attention skill changes across time in a 45-minute simulated driving test. METHOD: One hundred and twenty-nine community-dwelling older drivers volunteered to take part in the study. A range of driving scenarios was devised and implemented in a simulator setting to assess the driving skills of the participants. Visual attention skill, an important contributing factor to motor vehicle crashes, was assessed by the participant's reaction times to a sequence of 14 visual stimuli during the primary task of sustained driving. Repeated measures of analysis of variance (ANOVA) were undertaken to determine the effects of age and gender on the visual attention skill. Trend analysis was performed to investigate how repeated exposures to the visual stimulus affected the reaction time. RESULTS: The visual attention skill of older drivers was found to decline with age (F(1,126)) = 42.52, p value = 0.002), whereas the effect of gender was not significant. Participants increased their speed of reaction times for the first half of the testing then slowed down during the second half. CONCLUSION: That visual attention skill declined with age was consistent with the literature, and validated the driving simulator as an effective screening tool for older adult drivers. With rapid advancements in computer technology, the driving simulator will likely play an important role in assisting occupational therapists with off-road assessment of older drivers.     

Potential role of protein kinase C on the differentiation of erythroid progenitor cells

The effect of protein kinase C inhibitors, staurosporine and 1-(5-isoquinolinyl sulfonyl)-2-methyl piperazine(H7) onin vitro differentiation of erythroid progenitor cells which were isolated from spleens of mice infected with the anemia-inducing strain of Friend virus were examined. Erythropoietin-mediated differentiation of erythroid progenitor cells, as determined by the incorporation of⁵⁹Fe into protoporphyrin, was inhibited by staurosporine and H7 in a concentration-dependent manner. Scatchard analysis of the³H-phorbol-12, 13-dibutyrate binding to erythroid progenitor cells revealed that at the high affinity sites the dissociation constant was 22nM and the maximum number of³H-phorbol-12,13-dibutyrate binding sites per cell was approximately 3.7×10⁵. Cytosolic protein kinase C was isolated from erythroid progenitor cells and then purified by sequential column chromatography. Two isoforms of protein kinase C were found. Photoaffinity labeling of the purified protein kinase C samples with³H-phorbol 12-myristate 13-acetate followed by analysis of SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and autofluorography showed radiolabeled 82-KDa peptides. Radiolabeling of the 82-kDa peptides with³H-phorbol 12-myristate 13-acetate was almost completely blocked by excess unlabeled phorbol 12-myristate 13-acetate. Results of phorbol 12-myristate 13-acetate-promoted phosphorylation with the purified protein kinase C samples showed that the phosphorylation of 82-kDa peptides was increased as the concentration of phorbol 12-myristate 13-acetate was increased from 10⁻⁸ M to 10⁻⁴M. In light of the findings that erythroid progenitor cells possessed an abundance of protein kinase C and that staurosporine and H7 inhibited erythroid differentiation, it seemed likely that protein kinase C would play a role in the erythroid progenitor cell development.