Radical Retropubic Prostatectomy for Localized Prostate Cancer in Renal Transplant Patients

OBJECTIVE To investigate the feasibility of radical retropubic prostatectomy (RRP) in renal transplant recipients with clinically localized prostate cancer. METHODS A prospective protocol was established between August 2004 and November 2007. In that period, 8 patients diagnosed with localized prostate cancer were submitted to RRP, and their clinicopathologic data were reviewed. RESULTS The mean age (standard deviation) at surgery was 59.6 +/- 6.7 years (range, 49-67 years). All patients had TIC tumors, except for 1 with a T2A tumor. The mean preoperative prostate-specific antigen value was 4.5 +/- 1.8 ng/mL (range, 1.6-7.0 ng/mL). The mean interval between renal transplantation and RRP was 89.9 +/- 65.1 months (range, 40-209 months). The procedure was well tolerated without major complications, and all patients were discharged on the fifth postoperative day. There was no impairment to bladder descent caused by the presence of the allograft or the ureteroneocystostomy. Urethrovesical anastomosis was easily performed in all cases in the standard manner. Blood transfusion was needed in 2 patients (1 received 2 U and another 5 U of blood). The mean operative duration was 183 +/- 29.7minutes (range, 150-240 minutes), the mean estimated blood loss was 656 +/- 576 mL (range, 100-2000 mL), and no deterioration of graft function was observed. All patients were followed, and the mean follow-up was 10.5 months (range, 2-30 months). Prostate-specific antigen was undetectable in all cases during this time frame. CONCLUSIONS Radical retropubic prostatectomy in renal transplant patients is safe, effective, and can be easily performed in the same manner as described by Walsh, regardless of the presence of the allograft. The only necessary technical modification is the avoidance of ipsilateral lymphadenectomy to prevent damage to the transplanted organ. UROLOGY 72: 1362-1365, 2008. (C) 2008 Elsevier Inc.

Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis

Background and Purpose-Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H-2) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. Methods-The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. Results-Over half of CVT patients (52.1%) were heterozygous (H1H2) or homozygous (H2H2) carriers of the H-2 haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H2 haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). Conclusions-These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer`s disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer`s Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer`s disease.

Technical modifications in stabilisers and in bar removal in the Nuss procedure

Pectus excavatum is a congenital deformity that can require surgical treatment. Since Nuss proposed a correction technique, several modifications have been proposed in order to achieve more safety and efficiency in the placement and removal of both bars. Our objective is to describe the technique of placing and removing the bars by proposing three technical modifications: two in bar placement and one in the bar removal. We describe two cases where Nuss bars were placed and one case where the bar was removed as per the technical modification proposed herein. According to the original technique, bar stabilisers. were placed close to the lateral bar edges. We propose a more medial position in order to reduce bar displacement. New stabilisers were designed with central grooves in the posterior surface, which allow better sliding. The technical modification suitable for bar removal was the use of a protective film around the bars to protect the surrounding tissues from the sharp edges, and thereby minimise the risk of injuries. All the proposed modifications were performed without any additional surgical risk or perioperative complication. These three technical modifications can be easily and safety performed, and seem to reduce the risk of bleeding with no additional perioperative complications. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Crucial role of neutrophils in the development of mechanical inflammatory hypernociception

Neutrophil migration is responsible for tissue damage observed in inflammatory diseases. Neutrophils are also implicated in inflammatory nociception, but mechanisms of their participation have not been elucidated. In the present study, we addressed these mechanisms in the carrageenan-induced mechanical hypernociception, which was determined using a modification of the Randall-Sellito test in rats. Neutrophil accumulation into the plantar tissue was determined by the contents of myeloperoxidase activity, whereas cytokines and PGE(2) levels were measured by ELISA and radioimmunoassay, respectively. The pretreatment of rats with fucoidin (a leukocyte adhesion inhibitor) inhibited carrageenan-induced hypernociception in a dose- and time-dependent manner. Inhibition of hypernociception by fucoidin was associated with prevention of neutrophil recruitment, as it did not inhibit the hypernociception induced by the direct-acting hypernociceptive mediators, PGE(2) and dopamine, which cause hypernociception, independent of neutrophils. Fucoidin had no effect on carrageenan-induced TNF-alpha, IL-1 beta, and cytokine-induced neutrophil chemoattractant 1 (CINC-1)/CXCL1 production, suggesting that neutrophils were not the source of hypernociceptive cytokines. Conversely, hypernociception and neutrophil migration induced by TNF-alpha, IL-1 beta, and CINC-1/CXCL1 was inhibited by fucoidin, suggesting that neutrophils are involved in the production of direct-acting hypernociceptive mediators. Indeed, neutrophils stimulated in vitro with IL-1 beta produced PGE(2), and IL-1 beta-induced PGE(2) production in the rat paw was inhibited by the pretreatment with fucoidin. In conclusion, during the inflammatory process, the migrating neutrophils participate in the cascade of events leading to mechanical hypernociception, at least by mediating the release of direct-acting hypernociceptive mediators, such as PGE(2). Therefore, the blockade of neutrophil migration could be a target to development of new analgesic drugs.

Role of complement C5a in mechanical inflammatory hypernociceptio: potential use of C5a receptor antagonists to control inflammatory pain

particularly neutrophil chemoattraction. Herein, the role of C5a in the genesis of inflammatory hypernociception was investigated in rats and mice using the specific C5a receptor antagonist PMX53 (AcF-[OP(D-Cha)WR]). Experimental approach: Mechanical hypernociception was evaluated with a modification of the Randall-Selitto test in rats and electronic pressure meter paw test in mice. Cytokines were measured by ELISA and neutrophil migration was determined by myeloperoxidase activity. Key results: Local pretreatment of rats with PMX53 (60-180 mg per paw) inhibited zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception. These effects were associated with C5a receptor blockade since PMX53 also inhibited the hypernociception induced by zymosan- activated serum and C5a but not by the direct-acting hypernociceptive mediators, prostaglandin E-2 and dopamine. Underlying the C5a hypernociceptive mechanisms, PMX53 did not alter the cytokine release induced by inflammatory stimuli. However, PMX53 inhibited cytokine-induced hypernociception. PMX53 also inhibited the recruitment of neutrophils induced by zymosan but not by carrageenan or LPS, indicating an involvement of neutrophils in the hypernociceptive effect of C5a. Furthermore, the C5a-induced hypernociception was reduced in neutrophil-depleted rats. Extending these findings in rats, blocking C5a receptors also reduced zymosan- induced joint hypernociception in mice. Conclusions and implications: These results suggest that C5a is an important inflammatory hypernociceptive mediator, acting by a mechanism independent of hypernociceptive cytokine release, but dependent on the presence of neutrophils. Therefore, we suggest that inhibiting the action of C5a has therapeutic potential in the control of inflammatory pain.

Sexual differentiation of cortical spreading depression propagation after acute and kindled audiogenic seizures in the Wistar audiogenic rat (WAR)

Brain excitability diseases like epilepsy constitute one factor that influences brain electrophysiological features. Cortical spreading depression (CSD) is a phenomenon that can be altered by changes in brain excitability. CSD propagation was presently characterized in adult mate and female rats from a normal Wistar strain and from a genetically audiogenic seizure-prone strain, the Wistar audiogenic rat (WAR), both previously submitted (RAS(+)), or not (RAS(-)), to repetitive acoustic stimulation, to provoke audiogenic kindling in the WAR-strain. A gender-specific change in CSD-propagation was found. Compared to seizure-resistant animals, in the RAS- condition, mate and female WARs, respectively, presented CSD-propagation impairment and facilitation, characterized, respectively, by lower and higher propagation velocities (P<0.05). In contraposition, in the RAS(+) condition, mate and female WARs displayed, respectively, higher and tower CSD-propagation rates, as compared to the corresponding controls. In some Wistar and WAR females, we determined estrous cycle status on the day of the CSD-recording as being either estrous or diestrous; no cycle-phase-related differences in CSD-propagation velocities were detected. In contrast to other epilepsy models, such as Status Epilepticus induced by pilocarpine, despite the CSD-velocity reduction, in no case was CSD propagation blocked in WARs. The results suggest a gender-related, estrous cycle-phase-independent modification in the CSD-susceptibility of WAR rats, both in the RAS(+) and RAS(-) situation. (C) 2008 Elsevier B.V. All rights reserved.

Histopathology of the Hematopoietic Bone Marrow in the Temporomandibular Joint of Rats Subjected to Undernutrition and to Mandibular Condyle Fracture

Undernutrition can cause important functional and morphological alterations in the hematopoietic bone marrow (HBM). Degeneration of the HBM in malnourished individuals has been observed in the long bones, but none has been described in the cranial bones. Mandibular condyle fracture can lead to determine nutritional effects due to the high catabolism needed for the bone healing added to the difficulties of mastication. The aim of this study is to describe the histological aspect of HBM in the fractured mandibular condyle and in the temporal bone of malnourished rats. Thirty adult rats suffered unilateral mandibular condyle fracture and were divided into well-nourished (FG) and malnourished (MG) groups. In the MG the animals received a hypoproteic diet during the experiment. Histological sections of the temporomandibular joint were stained to visualize and quantify the HBM in this region at 24h, and 7, 15, 30, and 90 days post-fracture. At 24 hours, FG and MG showed hypocellularity and ischemic degeneration in the mandibular condyle and in the temporal bone. At 7 days, FG exhibited high cellularity in comparison with MG in the condyle; the temporal bone of both groups presented hypocellularity and degeneration. At 30 and 90 days, FG exhibited similar characteristics to those of the control; MG maintained the degeneration level mainly in the temporal bone. Malnutrition prejudices the regeneration of the HBM during a fracture healing in the temporomandibular joint. This fact contributes to a complete modification of the bone structure as well as to an impairment of the healing process.

Cyclic Fatigue Resistance of Rotary Nickel-Titanium Instruments Submitted to Nitrogen Ion Implantation

Introduction: The aim of this study was to assess cyclic fatigue resistance in rotary nickel-titanium instruments submitted to nitrogen ion implantation by using a custom-made cyclic fatigue testing apparatus. Methods: Thirty K3 files, size #25, taper 0.04, were divided into 3 experimental groups as follows: group A, 12 files exposed to nitrogen ion implantation at a dose of 2.5 x 10(17) ions/cm(2), accelerating voltage of 200 kV, currents of 1 mu A/cm(2), 130 degrees C temperature, and vacuum conditions of 10 x 10(-6) torr for 6 hours; group B, 12 nonimplanted files; and group C, 6 files submitted to thermal annealing for 6 hours at 130 degrees C. One extra file was used for process control. All files were submitted to a cyclic fatigue test that was performed with an apparatus that allowed the instruments to rotate freely, simulating rotary instrumentation of a curved canal (40-degree, 5-mm radius curve). An electric motor handpiece was used with a contra-angle of 16:1 at an operating speed of 300 rpm and a torque of 2 N-cm. Time to failure was recorded with a stopwatch in seconds and subsequently converted to number of cycles to fracture. Data were analyzed with the Student t test (P < .05). Results: Ion-implanted instruments reached significantly higher cycle numbers before fracture (mean, 510 cycles) when compared with annealed (mean, 428 cycles) and nonimplanted files (mean, 381 cycles). Conclusions: Our results showed that nitrogen ion implantation improves cyclic fatigue resistance in rotary nickel-titanium instruments. Industrial implementation. of this surface modification technique would produce rotary nickel-titanium instruments with a longer working life. (J Endod 2010;36:1183-1186)

Bacterial Adhesion on Smooth and Rough Titanium Surfaces After Treatment With Different Instruments

Background: Newly formed biofilm after implant debridement may challenge the long-term stability of peri-implant therapy. This in vitro study aimed to assess the roughness and adherence of Streptococcus sanguinis after treatment of smooth and rough titanium surfaces with an erbium-doped: yttrium, aluminum, and garnet (Er:YAG) laser, metal and plastic curets, and an air-powder abrasive system. Methods: Forty titanium disks with smooth-machined surfaces and 40 with sand-blasted and acid-etched surfaces were divided into the following treatment groups: Er:YAG laser; plastic curet; metal curet, and air-powder abrasive system. The surface roughness (roughness average [Raj) before and after treatments was determined using a profilometer. S. sanguinis (American Type Culture Collection 10556) was grown on treated and untreated specimens, and the amounts of retained bacteria on the surfaces were measured by the culture method. Rough and smooth surfaces with and without a suspension of S. sanguinis were also analyzed using scanning electron microscopy (SEM). Results: For smooth surfaces, the roughest surfaces were produced by metal curets (repeated - measures analysis of variance [ANOVA] and Tukey test; P<0.05). The rough-surface profile was not altered by any of the treatments (repeated-measures ANOVA; P>0.05). Rough surfaces treated with metal curets and air-powder abrasion showed the lowest level of bacteria] adhesion (two-way ANOVA and Tukey test; P<0.05). SEM analysis revealed distinct surface profiles produced by all devices. Conclusions: Metal curets are not recommended for smooth titanium surface debridement due to severe texture alteration. Rough surfaces treated with a metal curet and the air-powder abrasive system were less susceptible to bacterial adhesion, probably due to texture modification and the presence of abrasive deposits. J Periodontol 2009;80: 1824-1832.

Cysteine Cathepsins in Human Dentin-Pulp Complex

Introduction: Collagen-degrading matrix metalloproteinases (MMPs) are expressed by odontoblasts and present in dentin. We hypothesized that odontoblasts express other collagen-degrading enzymes such as cysteine cathepsins, and their activity would be present in dentin, because odontoblasts are known to express at least cathepsin D. Effect of transforming growth factor beta (TGF-beta) on cathepsin expression was also analyzed. Methods: Human odontoblasts and pulp tissue were cultured with and without TGF-beta, and cathepsin gene expression was analyzed with DNA microarrays. Dentin cathepsin and MMP activities were analyzed by degradation of respective specific fluorogenic substrates. Results: Both odontoblasts and pulp tissue demonstrated a wide range of cysteine cathepsin expression that gave minor responses to TGF-beta. Cathepsin and MMP activities were observed in all dentin samples, with significant negative correlations in their activities with tooth age. Conclusions: These results demonstrate for the first time the presence of cysteine cathepsins in dentin and suggest their role, along with MMPs, in dentin modification with aging. (J Endod 2010;36:475-481)

The Erosive Potential of 1% Citric Acid Supplemented by Different Minerals: An In Vitro Study

Purpose: The objective of the present in vitro study was to evaluate the effect of different minerals in combination with 1% citric acid on dental erosion. Materials and Methods: Ninety enamel samples were randomly allocated to nine groups (G1. pure 1% citric acid solution [control]. G2. with 1 mM Ca: G3 with 0 047 mM F, G4. with 1 mM Fe. G5. with 1 mM P, G6 with 1 mM Ca and 0 047 mM F. G7. with 1 mM Ca and 1 mM P: G8: with 1 mM Fe and 0.047 mM F, G9. with 1 mM Ca, 1 mM P. 0 047 rnM F and 1.0 mM Fe) The samples were subjected to six pH cycles, each consisting of immersion in pure or modified 1% citric acid (1 min) followed by storage in artificial saliva (59 min) Enamel wear was assessed using profilometry. Results: Data were analysed using analysis of variance and Tukey test (P < 0 05) Enamel loss (mean +/- SD) amounted to between 0 87 +/- 0 30 and 1 74 +/- 0 74 mu m but did not significantly differ among the groups Conclusions: The modification of 1% citric acid with different minerals did not have a protective effect on enamel erosion

Effect of ion supplementation of a commercial soft drink on tooth enamel erosion

Acidic soft drinks are potentially erosive for dental hard tissues. This in vitro study evaluated the effect of calcium, fluoride, iron and phosphate, supplemented alone or in combination to a commercial citric acid-based carbonated beverage on dental erosion. Ninety enamel samples (4 x 4 x 3 mm) were randomly allocated to nine groups (n = 10): G1 - pure beverage (control); G2 - with 1 mM Ca; G3 - with 0.047 mM F; G4 - with 1 mM Fe; G5 - with 1 mM P; G6 - with 1 mM Ca and 0.047 mM F; G7 - with 1 mM Ca and 1 mM P; G8 - with 1 mM Fe and 0.047 mM F; and G9 - with 1 mM Ca, 1 mM P, 0.047 mM F and 1.0 mM Fe. The samples were subjected to six pH cycles over a 24-h period. In each cycle, the samples were immersed in pure or modified beverage (1 min) and in artificial saliva (59 min). During the remaining period (18 h), the samples were maintained in artificial saliva. Enamel loss was assessed by profilometry (mm). Data were tested using ANOVA and Tukey`s tests (p < 0.05). Highest enamel losses were observed in the control group (G1) and in the groups containing Fe (G4 and G8). The groups containing Ca (G2 and G6) showed significantly less wear compared to control. In conclusion, the modification of an erosive soft drink with low concentrations of Ca with or without F may reduced its erosive potential.

Fatigue life and failure modes of crowns systems with a modified framework design

Objectives: To evaluate the effect of framework design on the fatigue life and failure modes of metal ceramic (MC, Ni-Cr alloy core, VMK 95 porcelain veneer), glass-infiltrated alumina (ICA, In-Ceram Alumina/VM7), and veneered yttria-stabilized tetragonal zirconia polycrystals (Y-TZP, IPSe.max ZirCAD/IPS e.max,) crowns. Methods: Sixty composite resin tooth replicas of a prepared maxillary first molar were produced to receive crowns systems of a standard (MCs, ICAs, and Y-TZPs, n = 10 each) or a modified framework design (MCm, ICAm, and Y-TZPm, n = 10 each). Fatigue loading was delivered with a spherical steel indenter (3.18 mm radius) on the center of the occlusal surface using r-ratio fatigue (30-300 N) until completion of 10(6) cycles or failure. Fatigue was interrupted every 125,000 cycles for damage evaluation. Weibull distribution fits and contour plots were used for examining differences between groups. Failure mode was evaluated by light polarized and SEM microscopy. Results: Weibull analysis showed the highest fatigue life for MC crowns regardless of framework design. No significant difference (confidence bound overlaps) was observed between ICA and Y-TZP with or without framework design modification. Y-TZPm crowns presented fatigue life in the range of MC crowns. No porcelain veneer fracture was observed in the MC groups, whereas ICAs presented bulk fracture and ICAm failed mainly through the veneer. Y-TZP crowns failed through chipping within the veneer, without core fractures. Conclusions: Framework design modification did not improve the fatigue life of the crown systems investigated. Y-TZPm crowns showed comparable fatigue life to MC groups. Failure mode varied according to crown system. (C) 2010 Elsevier Ltd. All rights reserved.