Locul medicaţiei alfablocante selective în tratamentul prostatitei cronice

Abstract Although the term “chronis prostatitis" has been used for different entities that cannot be easily separated, it has been estimated that up to half of all men suffer from symptoms of prostatitis at some point in their lives. Having these aspects in mind, the authors have tried, in this prospective study, to evaluate the impact of introducing selective alfa blockers in the treatment of chronic prostatitis(Tamsulosin and Alfuzosine).The including criterias were: age between 30 and 55; at least one episode of prostatitis in the past; a normal prostate size and a postvoid residual urine volume< 20 ml.Each patient has recived a file containing general recom andations and has filled out two questionforms (NIH-CPSID Chronic Prostatitis Symptom Index Domain), to evaluate the situation before and three months from the treatment after 3 month. Based on this we have evaluated the benefits of the treatment from the point of view of: pain, urinary symptoms and a better quality of life. The preliminary results show that urinary simptoms have been ameliorated and that almost all the patients have noticed the benefits of selective alfa blockers. The ondulant evolution of the illness raises numerous obstacles for urologists trying to find the ideal treatment for prostatitis Rezumat Pornind de la dificultăţile de diagnostic şi de tratament ale prostatitei cronice (unanim recunoscută in lumea urologică) şi de la estimarea că aproape jumătate din numărul bărbaţilor vor prezenta simptome de prostatită la un moment dat, am încercat să evaluăm într-un studiu prospectiv, aflat în desfăşurare, impactul medicaţiei alfablocante selective (Tamsulosin, Alfuzosin SR) asupra simptomatologiei acestei patologii. Au fost incluşi în studiu pacienţi cu vârsta între 30 şi 55 de ani, cu cel puţin un episod de prostatită în antecedente, dimensiunile prostatei (evaluate echografic) în limite normale, reziduu vezical d" 20ml. Fiecare pacient a primit un dosar care cuprinde o fişă cu recomandări generale şi două chestionare de evaluare (NIHCPSI) la început şi după 3 luni de la tratament. Schema de tratament a inclus: antibioterapie, tratament cu antiinflamatorii, alfablocantul selectiv (Tamsulosin sau Alfuzosin). Am introdus pentru pacienţii care admiteau un consum important de proteine animale şi tratament cu Allopurinol, dar lotul este încă prea mic pentru a trage concluzii. Pe baza chestionarelor am evaluat atât beneficiile tratamentului sub raportul durerii (totalul punctelor 1, 2, 3, 4), al simptomelor urinare (totalul punctelor 5 şi 6), cât şi impactul asupra calităţii vieţii (7, 8, 9). Rezultatele preliminare ale studiului nostru la lotul respectiv indică benefică asocierea alfablocantelor, în special pentru ameliorarea simptomelor urinare. Considerăm, totodată, că evoluţia ondulantă a bolii ridică numeroase obstacole în calea stabilirii unui tratament ideal în prostatita cronică

Predictive factors for complications in rigid and semirigid retrograde ureteroscopy

Clinica de Urologie şi Transplant Renal, Spital Clinic “Dr. CI Parhon” Iaşi, Al V-lea Congres de Urologie, Dializă şi Transplant Renal din Republica Moldova cu participare internaţională (1-13 iunie 2011)Background. Currently, ureteroscopy is a worldwide procedure with varied number of diagnostic and therapeutic possibilities, including treatment of stones, upper urinary tract tumors, strictures, placement of difficult ureteral stents, and diagnosis of filling defects or haematuria of unknown origin. However, the technique has complications including bleeding, fever and sepsis, ureteral perforation, false passage, urinoma, strictures and, rarely, ureteral avulsion. PURPOSE. Our purpose was to evaluate the ureteroscopies with long hospitalization and to analyse the preoperative predictive factors for the complications. METHODS. We retrospectively reviewed all 342 files of the patients who underwent retrograde ureteroscopy for different reasons between january 2005 and december 2009. Data were abstracted on period of hospitalization, indications for the procedure (urolithiasis – site, number and size, reno-ureteral haematuria, filling defects), bioumoral status, outcome and complications of the method. RESULTS. The mean hospitalization time was 6,53 ± 2,09 days, with a preoperative period of 3,37 ± 1,74 days and a postoperatory time of 2,16 ± 1,08 days. Only 40 patients (11,7%) have exceled this postoperatory period due to a complicated outcome, meanwhile the preoperative time was tidely corelated with the diagnostic imaging methods. The success rate of all therapeutic procedures was 84,74% and the overall and major complication rates was 23,09% and 4,97%. The analysis of preoperative factors showed that preoperative bacteriuria is statistically correlated with postoperatory complications, such as fever and sepsis (p<0.001), and persistent haematuria is linked to stone size and ureteral stent size placed at the end of the procedure (8Ch) without having statistical significance. CONCLUSIONS. Our experience suggests that carefully performed retrograde ureteroscopy is a superb tool for the urologist, either for diagnostic or therapeutic purposes. However, when performing an ureteroscopy, one should always bear in mind the possibility of serious complications, including ureteral avulsion or perforation

NMDA Receptors on Non-Dopaminergic Neurons in the VTA Support Cocaine Sensitization

The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic plasticity in the mesolimbic dopamine (DA) circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA) DA neurons, and its association with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressing Cre recombinase under the control of the endogenous dopamine transporter gene (NR1(DATCre) mice).Using an additional NR1(DATCre) mouse transgenic model, we demonstrate that while the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remain intact in NR1(DATCre) mice. Since VTA DA neurons projecting to the prefrontal cortex and amygdala express little or no detectable levels of the dopamine transporter, it has been speculated that NMDA receptors in DA neurons projecting to these brain areas may have been spared in NR1(DATCre) mice. Here we demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA neurons, including those exhibiting undetectable DAT expression levels in our NR1(DATCre) transgenic model, and that application of an NMDAR antagonist within the VTA of NR1(DATCre) animals still blocks sensitization to cocaine.These results eliminate the possibility of NMDAR mediated neuroplasticity in the different DA neuronal subpopulations in our NR1(DATCre) mouse model and therefore suggest that NMDARs on non-DA neurons within the VTA must play a major role in cocaine-related addictive behavior

Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours

Selective Deletion of PTEN in Dopamine Neurons Leads to Trophic Effects and Adaptation of Striatal Medium Spiny Projecting Neurons

The widespread distribution of the tumor suppressor PTEN in the nervous system suggests a role in a broad range of brain functions. PTEN negatively regulates the signaling pathways initiated by protein kinase B (Akt) thereby regulating signals for growth, proliferation and cell survival. Pten deletion in the mouse brain has revealed its role in controlling cell size and number. In this study, we used Cre-loxP technology to specifically inactivate Pten in dopamine (DA) neurons (Pten KO mice). The resulting mutant mice showed neuronal hypertrophy, and an increased number of dopaminergic neurons and fibers in the ventral mesencephalon. Interestingly, quantitative microdialysis studies in Pten KO mice revealed no alterations in basal DA extracellular levels or evoked DA release in the dorsal striatum, despite a significant increase in total DA tissue levels. Striatal dopamine receptor D1 (DRD1) and prodynorphin (PDyn) mRNA levels were significantly elevated in KO animals, suggesting an enhancement in neuronal activity associated with the striatonigral projection pathway, while dopamine receptor D2 (DRD2) and preproenkephalin (PPE) mRNA levels remained unchanged. In addition, PTEN inactivation protected DA neurons and significantly enhanced DA-dependent behavioral functions in KO mice after a progressive 6OHDA lesion. These results provide further evidence about the role of PTEN in the brain and suggest that manipulation of the PTEN/Akt signaling pathway during development may alter the basal state of dopaminergic neurotransmission and could provide a therapeutic strategy for the treatment of Parkinson's disease, and other neurodegenerative disorders

Real-Space Mesh Techniques in Density Functional Theory

This review discusses progress in efficient solvers which have as their foundation a representation in real space, either through finite-difference or finite-element formulations. The relationship of real-space approaches to linear-scaling electrostatics and electronic structure methods is first discussed. Then the basic aspects of real-space representations are presented. Multigrid techniques for solving the discretized problems are covered; these numerical schemes allow for highly efficient solution of the grid-based equations. Applications to problems in electrostatics are discussed, in particular numerical solutions of Poisson and Poisson-Boltzmann equations. Next, methods for solving self-consistent eigenvalue problems in real space are presented; these techniques have been extensively applied to solutions of the Hartree-Fock and Kohn-Sham equations of electronic structure, and to eigenvalue problems arising in semiconductor and polymer physics. Finally, real-space methods have found recent application in computations of optical response and excited states in time-dependent density functional theory, and these computational developments are summarized. Multiscale solvers are competitive with the most efficient available plane-wave techniques in terms of the number of self-consistency steps required to reach the ground state, and they require less work in each self-consistency update on a uniform grid. Besides excellent efficiencies, the decided advantages of the real-space multiscale approach are 1) the near-locality of each function update, 2) the ability to handle global eigenfunction constraints and potential updates on coarse levels, and 3) the ability to incorporate adaptive local mesh refinements without loss of optimal multigrid efficiencies.Comment: 70 pages, 11 figures. To be published in Reviews of Modern Physic

Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum

Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2), thyrotropin-releasing hormone (TRH), brain derived neurotrophic factor (BDNF), c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx)-1, and heme oxygenase-1 (Hmox-1). These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to provide some insight into the neuroadaptive potentials of the brain when repeatedly exposed to drugs of abuse

Tuneable vibration absorber using acceleration and displacement feedback

This study is concerned with the analysis and design of a tuneable vibration absorber, which is composed by a flexible beam with a clamping block in the middle and two masses symmetrically mounted at the two ends. The free length of the beam is used to accommodate piezoelectric strain actuators. The two masses at the ends are equipped with inertial accelerometers. This arrangement is used to generate two independent acceleration feedback control loops that produce virtual mass effects, which shift the absorbing frequency of the device. Another arrangement is also studied where the two accelerometer outputs are time-integrated twice in order to implement displacement feedback loops that change the beam stiffness to shift the characteristic frequency of the device. The two feedback approaches are first analysed theoretically, using a mobility-impedance model, and then experimentally on a prototype absorber unit. The stability of the feedback loops is studied using the Nyquist criterion in order to estimate the limits on the tuneable range of frequencies which are set by the maximum stable feedback gains. The study indicates that the stability margins for the acceleration feedback loops substantially depend on the application of an appropriate low-pass filter. On the contrary, the implementation of displacement feedback gives better stability margins

Theoretical an Experimental Analysis of a Tuneable Vibration Absorber using Acceleration and Displacement Feedback

This study is concerned with the analysis and design of a tuneable vibration absorber, which is composed by a flexible beam with a clamping block in the middle and two masses symmetrically mounted at two ends. The free length of the beam is used to accommodate piezoelectric strain actuators. The two masses at the ends are equipped with inertial accelerometers. Firstly, this arrangement is used to generate two independent acceleration feedback control loops that produce virtual mass effects, which consequently shift the absorbing frequency of the device. Secondly, the accelerometer output is time-integrated twice in order to implement displacement feedback loops that generate virtual changes in the beam stiffness to shift the characteristic frequency of the device. The two feedback approaches are first analysed theoretically, using a mobility-impedance approach, and then experimentally on a prototype absorber unit. The stability of the feedback loops is studied using the Nyquist criterion in order to estimate the limits on the tuneable range of frequencies which are set by the maximum stable feedback gain. The study indicates that the stability margins for the acceleration feedback loops substantially depend on the application of an appropriate low-pass filter. This is due to unfavourably large amplitudes of the sensor-actuator frequency response functions at higher frequencies. In contrast, implementation of displacement feedback naturally yields a favourable roll-off at higher frequencies and gives better stability margins. The maximum feedback gain is however limited at low-frequencies due to the frequency response of the analogue double-integrator. Nevertheless, the use of an integrator with a cut-off frequency low enough results in good stability margins that allow for a relatively large shift of the characteristic frequency of the absorber by the active displacement feedbackcontrol