Amantadine Inhibits SARS-CoV-2 In Vitro.

Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis.

The cytoskeleton in 'couch potato-ism': Insights from a murine model of impaired actin dynamics.

Evidence for a critical pathophysiological role of aberrant cytoskeletal dynamics is being uncovered in a growing number of neuropsychiatric syndromes. A sedentary lifestyle as well as overt psychopathology is prevalent in patients with the metabolic syndrome. Using mice deficient in gelsolin (Gsn-/-), a crucial actin-severing protein, we here investigated reduced actin turnover as a potential common driver of metabolic disturbances, sedentary behavior, and an anxious/depressive phenotype. Gelsolin deficiency resulted in reduced lifespan. As compared to wildtype controls, Gsn-/- mice (~ 9 weeks) fed a high-fat diet (HFD) over a span of 12 weeks showed increased body weight gain, fat mass, hepatic steatosis, and adipocyte hypertrophy as well as a significantly reduced respiratory quotient. Moreover, increased rigidity of the actin cytoskeleton in mice on HFD induced mRNA expression of Acc1, Acc2, Fasn, and Lipe, key genes involved in fatty acid metabolism in the liver. Glucose tolerance and insulin sensitivity were worsened in Gsn-/- HFD relative to Gsn+/+ HFD mice. Hypertension in Gsn-/- mice was associated with reduced endothelial NO synthase (eNOS) mRNA expression and reduced eNOS protein trafficking to the plasma membrane. Furthermore, acetylcholine-induced cGMP production and relaxation of aortic rings were impaired by actin filament stabilization. Gsn-/- mice on HFD displayed reduced corticosterone concentrations and reduced energy expenditure as compared to Gsn+/+ HFD mice. Moreover, Gsn-/- HFD mice displayed an overall pattern of hypoactive and anxious/depressive-like behavior. In aggregate, our results demonstrate that impaired actin filament dynamics promote the development of key behavioral and physiological aspects of the metabolic syndrome.

Measuring the potency labelling of onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin (®)) in an LD50 assay.

The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin(®)) are compared in the Xeomin(®) batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox(®) and Xeomin(®) can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs.

Expression of the non-gastric H+/K+ ATPase ATP12A in normal and pathological human prostate tissue.

Altered cellular proton handling and cell volume regulation are hallmarks of tumorigenesis. To investigate a possible involvement of the non-gastric H(+)/K(+) ATPase ATP12A (ATP1AL1) in prostate cancer, we performed immunohistochemistry in formalin-fixed, paraffin-embedded histological sections from benign and malignant human prostate lesions. Normal prostate tissue displayed a membrane-bound ATP12A staining with focal accumulated pattern, whereas in the benign prostate hyperplasia (BPH) and cancerous prostate tissue (tumor grade I-III) the protein appears to be displaced in the luminal cells of the glandular epithelium. Hence, the expression pattern of ATP12A is markedly altered in BPH and prostate cancer. To test for altered gene expression of ATP12A we performed quantitative reverse transcriptase PCR (QRT-PCR) in normal (tumor-free) prostate tissue, BPH and tumor stages I-III using a prostate cancer cDNA array. However, no significantly different expression levels could be detected in the various disease states compared to normal tissue, which contrasts the findings from immunohistochemistry and points to the possibility of altered post-translational processing and/or sorting of the protein. We further show that ATP12A mRNA is expressed at different levels in PC-3 and LNCaP prostate cancer cells, with a significant ~26-fold higher expression in the latter cell type. Protein expression in these tumor cell lines was verified by Western blot.

Stress worsens endothelial function and ischemic stroke via glucocorticoids.

BACKGROUND AND PURPOSE: Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model. METHODS: 129/SV mice were treated with glucocorticoid receptor antagonist mifepristone (25 mg kg(-1)/d) or vehicle and exposed to 28 days of chronic stress consisting of exposure to rat, restraint stress, and tail suspension. Heart rate and blood pressure were continuously recorded by telemetry. Endothelial nitric oxide synthase mRNA and protein expression as well as superoxide production and lipid hydroperoxides were quantified. Endothelium-dependent vasorelaxation was measured in aortic rings. Ischemic lesion volume was quantified after 30 minutes filamentous middle cerebral artery occlusion and 72 hours reperfusion. RESULTS: Chronic stress caused a significant increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Animals exposed to chronic stress showed major increases in ischemic lesion size. These deleterious effects of stress were completely reversed by treatment with mifepristone. CONCLUSIONS: Chronic stress increases stroke vulnerability likely through endothelial dysfunction, which can be reversed by a glucocorticoid receptor antagonist.

Studies on the dissociation of botulinum neurotoxin type A complexes.

UNLABELLED: The neurotoxins produced by the various strains of the anaerobic bacterium Clostridium botulinum naturally occur associated with complexing proteins which serve to protect the neurotoxins from the harsh environment of the mammalian gastrointestinal tract during bacterial invasion of the host. Three different complex species with the discrete sizes 19S (900 kDa, LL complex), 16S (500 kDa, L complex) and 12S (300 kDa, M complex) may be isolated from C. botulinum type A cultures. However, to affect their target cells these complexes must dissociate releasing the free 150 kDa neurotoxin. This study assesses the stability of these Clostridium botulinum neurotoxin serotype A (BoNT/A) complexes and identifies factors which influence their dissociation. The knowledge gained with purified toxin complexes was subsequently employed to analyze the presence of such complexes in the freeze or spray-dried commercial BoNT/A products Botox and Dysport in comparison to the complexing protein free product Xeomin. Purified 900 kDa and 500 kDa toxin complex preparations show a pH and time dependent release of the 150 kDa neurotoxin with a half-life of less than a minute at pH values >7.0. At pH values of 6.25 or less, the complexes are stable. Furthermore, dilution of concentrated 900 kDa complexes leads to dissociation into 500 kDa, neurotoxin containing complexes. Addition of sodium chloride as contained in isotonic saline leads to further disruption of these complexes resulting in the release of the free 150 kDa neurotoxin. Examination of the commercial botulinum neurotoxin products Botox and Dysport using the same analytical procedures leads to the same conclusion: the dilution, drying and reconstitution processes of these products lead to a complete dissociation of 900 kDa complexes and 85% or more of neurotoxin are present in free form. CONCLUSION: BoNT A toxin complexes have evolved to quickly respond to specific environmental changes by efficient release of the neurotoxin. During pharmaceutical production and reconstitution of BoNT A products, the same principles effect the quantitative dissociation of 900 kDa complexes and release of free neurotoxin prior to injection into target tissues.

Addition of lidocaine suppositories to periprostatic nerve block enhances pain control in prostate biopsies: a placebo-controlled randomized trial.

PURPOSE: The aim of this study was to evaluate the efficacy of a combined topical and local anesthesia consisting of a transrectal lidocaine suppository followed by periprostatic nerve block (PNB) in comparison to the combination of transrectally applied lidocaine gel followed by PNB and PNB alone as methods of reducing pain during transrectal prostate biopsy. PATIENTS AND METHODS: 100 patients were randomized to four groups and received either a placebo suppository or 10 ml of 2% lidocaine gel or a suppository containing 60 or 120 mg of lidocaine 1 h before biopsy. Additionally, every patient received a PNB using 5 ml 2% lidocaine. After performing an extensive transrectal ultrasound-guided biopsy, pain was evaluated using a visual pain scale. RESULTS: The mean pain score in the placebo group was 3.4, in the lidocaine gel group it was 3.7, and in the 60 or 120 mg lidocaine suppository groups it was 2.4 and 2.5, respectively. No patient showed vegetative symptoms like sweating or symptomatic hypotonia and no patient had severe pain. CONCLUSION: The addition of lidocaine suppositories to PNB as a form of combined anesthesia showed a significantly better pain reduction than the addition of lidocaine gel to PNB or PNB alone.

Impact of actin filament stabilization on adult hippocampal and olfactory bulb neurogenesis.

Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis.

Lack of gelsolin promotes perpetuation of atrial fibrillation in the mouse heart.

PURPOSE: Gelsolin (gsn) is involved in the reorganization of the cytoskeleton, thereby modulating cardiomyocytal L-type Ca(2+) channels. We investigated global cardiac electrophysiological characteristics in a gsn-deficient (gsn(-/-)) mouse strain. METHODS: Using transvenous catheterization, atrial and ventricular stimulation were performed in 15 male mice [eight gsn(-/-), seven wild-type (gsn(+/+))]. Surface ECG, standard electrophysiological parameters, and inducibility of atrial fibrillation (AF) were evaluated. RESULTS: The surface ECG showed shorter PQ (37.8 +/- 4.6 versus 42.9 +/- 2.7 ms; P = 0.02), but longer QRS (16.5 +/- 1.8 versus 13.9 +/- 1.2 ms; P = 0.005) and QT intervals (38.5 +/- 2.2 versus 35.6 +/- 2.4 ms, P = 0.03) in gsn(-/-). Gsn(-/-) exhibited significantly higher susceptibility to induction of prolonged AF episodes > or =60 s [six of eight gsn(-/-) versus one of seven gsn(+/+); P = 0.04]. Sustained AF episodes > or =10 min were observed in 50% of the gsn-deficient animals. CONCLUSIONS: Gsn deficiency results in perpetuation of inducible episodes of atrial fibrillation. Altered L-type Ca(2+) currents and disturbed Ca(2+) handling known to be associated to gsn deficiency likely contribute to this effect.

[The influence of bone quality and the fixation procedure on the primary stability of cementless implanted tibial plateaus]. / Der Einfluss der Knochenmineraldichte und des Verankerungsverfahrens auf die Primärstabilitat von zementfrei implantierten Tibiakomponenten.

BACKGROUND: An overview of prospective studies on cementless and cemented primary knee joint endoprosthetics carried out between 1988 and 2004 reveals that the aseptic tibial loosening rate of cemented prostheses implanted with fixed meniscal bearings amounts to 2-6% within a period of 4-14 years, while cementless implanted prostheses show loosening rates of up to 28% within a period of 4-10 years. If these results arise from a lack of proper initial osseointegration as a result of insufficient primary stability, and how this is influenced by the tibial bone quality and the tibial fixation procedure has not yet been investigated. MATERIALS AND METHODS: Tibial plateaus were press-fit implanted, both screwed and unscrewed, into each of six pairs of tibial heads from corpses. Stability testing was conducted applying eccentric axial load, shear and torsion. RESULTS: The average amounts of relative movement at the medial and lateral plateau are clearly different in the screwed version and the unscrewed version when loaded axially, but the difference was significant (p = 0.016) only at the medial plateau. Relative movements under shear and torsion showed no significant differences. The bone density of the tibial metaphyses had no significant effect on the primary stability of the cementless implanted tibial plateau. CONCLUSION: When using cementless knee endoprostheses, the fixation of the tibial plateau with screws--in addition to a flawless press-fit and form-fit customization of the tibial head--appears indispensable for guaranteeing proper osseointegration under physiological axial loads.

Comparison of lidocaine suppositories and periprostatic nerve block during transrectal prostate biopsy.

The aim of this randomized prospective and partially double-blind study was to evaluate the efficacy of transrectal lidocaine applied as suppositories in comparison to periprostatic infiltration as methods of reducing pain during transrectal prostate biopsy. 100 patients were randomized to four groups and received either a suppository containing 60 mg of lidocaine 2 h before biopsy, a 120-mg lidocaine suppository 1 h before biopsy, a 120-mg lidocaine suppository 2 h before biopsy, or they were anaesthetized with a periprostatic infiltration of 5 ml 2% lidocaine. In all patients the same 10-core transrectal biopsy technique was performed. Pain was evaluated using a visual pain scale ranging from 0 to 10 points. The mean pain score in the 60-mg (2 h), 120-mg (1 h), and 120-mg (2 h) lidocaine suppository groups was 3.63, 3.56, and 3.58 respectively. The mean pain score of patients receiving periprostatic infiltration was 1.80. No patient showed vegetative symptoms like sweating or hypotonia. No patient had severe pain. Eight of the 9 patients with no pain were in the periprostatic injection group. Thus, all lidocaine suppositories showed a good analgesic effect although a significantly better pain reduction was achieved by periprostatic lidocaine infiltration.

The use of Duloxetine in the treatment of male stress urinary incontinence.

Stress urinary incontinence (SUI) is a known complication after prostate surgery. To date no pharmacologic treatment is available. Currently Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is available for women with SUI. This study investigates the effect of Duloxetine on men with SUI after prostate surgery. 56 patients were included in our study. 49 after radical prostatectomy and 7 after TURP. All patients were initially treated with pelvic floor exercises. Thereafter 40 mg Duloxetine was administered twice daily. When taking Duloxetine, the average use of incontinence pads decreased from 3.3 to 1.5 per day. 14 patients needed no and 18 a single pad per day. Most patients reported mild and temporary side effects, 13 patients assessed them to be moderate and 9 being severe. The results of this off-label use show that Duloxetine is effective in men with SUI after prostate surgery even if standard pelvic floor exercises have failed.

Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury.

Acetylation/deactylation of histones is an important mechanism to regulate gene expression and chromatin remodeling. We have previously demonstrated that the HDAC inhibitor trichostatin A (TSA) protects cortical neurons from oxygen/glucose deprivation in vitro which is mediated--at least in part--via the up regulation of gelsolin expression. Here, we demonstrate that TSA treatment dose-dependently enhances histone acetylation in brains of wildtype mice as evidenced by immunoblots of total brain lysates and immunocytochemical staining. Along with increased histone acetylation dose-dependent up regulation of gelsolin protein was observed. Levels of filamentous actin were largely decreased by TSA pre-treatment in brain of wildtype but not gelsolin-deficient mice. When exposed to 1 h filamentous occlusion of the middle cerebral artery followed by reperfusion TSA pre-treated wildtype mice developed significantly smaller cerebral lesion volumes and tended to have improved neurological deficit scores compared to vehicle-treated mice. These protective effects could not be explained by apparent changes in physiological parameters. In contrast to wildtype mice, TSA pre-treatment did not protect gelsolin-deficient mice against MCAo/reperfusion suggesting that enhanced gelsolin expression is an important mechanism by which TSA protects against ischemic brain injury. Our results suggest that HDAC inhibitors such as TSA are a promising therapeutic strategy for reducing brain injury following cerebral ischemia.

Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9.

AIMS: Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic ligand bacterial DNA in the myocardium. We therefore studied the role of TLR9 in myocardial inflammation and cardiac contractility. METHODS AND RESULTS: Wild-type (WT, C57BL/6) and TLR9-deficient (TLR9-D) mice and isolated cardiomyocytes were challenged with synthetic bacterial DNA (CpG-ODN). Myocardial contractility as well as markers of inflammation/signalling were determined. Isolated cardiomyocytes incorporated fluorescence-marked CpG-ODN. In WT mice, CpG-ODN caused a robust response in hearts demonstrated by increased levels of tumour necrosis factor (TNF-alpha), interleukin (IL)-1beta, IL-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappaB activity. This inflammatory response was absent in TLR9-D mice. Under similar conditions, contractility measurements of isolated ventricular cardiomyocytes demonstrated a TLR9-dependent loss of sarcomeric shortening after CpG-ODN exposure. This observation was iNOS dependent as the application of a specific iNOS inhibitor reversed sarcomeric shortening to normal levels. CONCLUSION: Our data suggest that bacterial DNA contributes to myocardial cytokine production and loss of cardiomyocyte contractility via TLR9.

5-HT receptor regulation of neurotransmitter release.

Serotoninergic neurons in the central nervous system impinge on many other neurons and modulate their neurotransmitter release. This review focuses on 1) the function of presynaptic 5-hydroxytryptamine (5-HT) heteroreceptors on axon terminals of central cholinergic, dopaminergic, noradrenergic, or GABAergic neurons and 2) the role of GABAergic interneurons expressing 5-HT heteroreceptors in the regulation of acetylcholine, dopamine, or noradrenaline release. In vitro studies on slices or synaptosomes and in vivo microdialysis experiments have shown that 5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(2C), 5-HT(3), and/or 5-HT(4) heteroreceptors mediate this modulation. 5-HT(1B) receptors on neocortical cholinergic, striatal dopaminergic, or hippocampal GABAergic axon terminals are examples for release-inhibiting 5-HT heteroreceptors; 5-HT(3) receptors on hippocampal GABAergic or 5-HT(4) receptors on hippocampal cholinergic axon terminals are examples for release-facilitating 5-HT heteroreceptors. GABA released from GABAergic interneurons upon activation of facilitatory 5-HT receptors, e.g., 5-HT(2A) or 5-HT(3) receptors, mediates inhibition of the release of other neurotransmitters such as prefrontal neocortical dopamine or neocortical acetylcholine release, respectively. Conversely, attenuated GABA release in response to activation of inhibitory 5-HT heteroreceptors, e.g., 5-HT(1A) or 5-HT(1B) receptors on GABAergic interneurons is involved in paradoxical facilitation of hippocampal acetylcholine and striatal dopamine release, respectively. Such 5-HT heteroreceptors are considered potential targets for appropriate 5-HT receptor ligands which, by enhancing the release of a relevant neurotransmitter, can compensate for its hypothesized deficiency in distinct brain areas. Examples for such deficiencies are the impaired release of hippocampal or neocortical acetylcholine, striatal dopamine, and hippocampal or neocortical noradrenaline in disorders such as Alzheimer's disease, Parkinson's disease, and major depression, respectively.

The intraindividual agreement of the bone density of the human proximal tibia.

The interindividual variability in the biomechanical properties of cadaver bones has remained an unsolved problem in biomechanical investigation procedures. For this reason, it is postulated to use matched bone pairs from the same individual for comparative biomechanical tests. The rationale behind this procedure is based on the assumption that biomechanically similar behaviour is to be expected in an intraindividual rather than an interindividual comparison. Systematic studies confirming this thesis were performed on the human femur. However, investigations regarding the intraindividual properties of the proximal tibial metaphysis with respect to the underlying bone densities, have not yet been performed. In order to verify the hypothesis that matched proximal tibial metaphyses from the same donor imply corresponding bone density values, densitometric measurements (pQCT) were performed in 14 matched cadaver tibias (average age 61 years, 9 men, 5 women) which were fresh-frozen at -40 degrees C after removal. After statistical analysis of the bone density values, five tibial pairs were identified as differing on the basis of missing correlations and the existence of systematic differences within the pairwise data. In other words, only about 2/3 of the data in the random sample available was classified as comparable. As the bone density measured by pQCT technique significantly correlates with the biomechanical properties of the bone, it can be concluded from the test result available that matched human tibiae show no concurring bone density values in 1/3 of cases. Thus the pairing of corpse tibiae does not necessarily imply suitability for comparative biomechanical experiments.

Supervision, transference and countertransference.

The author discusses supervision, transference and countertransference as seen in the context of the clinical case of a patient who had been first seen as a training analysis case and who later, in a fortuitous way, was treated by the supervisor of the training analysis. The supervisor, who in the first instance did not recognize the patient, discusses the reasons for this unusual experience in terms of the presence and absence of transference during the analysis of this patient as a training case and the problems inherent in the task of supervising. The patient's feelings towards the first and the second analyst and the vicissitudes of transference and countertransference during the supervision of the training analysis and its influence on the presentation of the analytical sessions by the student are also detailed and discussed. The question of recorded supervision presentations and their possible influence on the dynamics of supervision is raised.

Prostate biopsy in Central Europe: results of a survey of indication, patient preparation and biopsy technique.

OBJECTIVE: We surveyed urologists in Austria, Germany and Switzerland regarding their standard approach to prostate biopsy. METHODS: Participants of Austrian and German urological meetings were asked to fill out a survey form; additionally, this was mailed to all Swiss urologists. RESULTS: 304 surveys are available for analysis. 97% of participants perform a biopsy if digital rectal examination is abnormal. 63% use 4 ng/ml PSA (prostate-specific antigen) as cut-off. Age-related reference ranges are used by 54%, free PSA by 57%. 22% use PSA density, 55% PSA velocity. Overall 61% require a written consent, with 85, 86 and 25% in Austria, Germany and Switzerland. 96% of the urologists prescribe a quinolone antibiotic with a wide range regarding the start and end of drug therapy. 77% offer some kind of anaesthesia. Periprostatic injection of a local anaesthetic drug is used by 36%, lidocaine gel by 27%. 91% perform the biopsies transrectally under ultrasound guidance. Digitally guided biopsies are used by 11%. Only 3 participants perform perineal biopsies. The mean number of cores per biopsy session is 9.2, the maximum number of cores is 15.3 as a mean. Participants will stop performing any further biopsies if the patient already had a mean of 3.5 biopsy sessions. CONCLUSIONS: The majority of urologists in Central Europe prescribe a quinolone antibiotic and recommend some type of analgesia. The majority has abandoned the sextant technique and increases the number of cores in the case of rebiopsy. Biopsies are stopped after a mean of 3.5 sessions.

The NAD(P)H oxidase inhibitor apocynin improves endothelial NO/superoxide balance and lowers effectively blood pressure in spontaneously hypertensive rats: comparison to calcium channel blockade.

The vascular NAD(P)H oxidase contributes to endothelial dysfunction and high blood pressure in the spontaneously hypertensive rat by enhancing superoxide production. We investigated the effects of apocynin, a NAD(P)H oxidase inhibitor, on blood pressure and vascular radical and nitric oxide formation in SHR and compared its effects to the calcium channel blocker nifedipine. Apocynin (over four weeks) lowered systolic blood pressure significantly and as effectively as nifedipine. Both apocynin and nifedipine significantly reduced superoxide production. In parallel, vascular nitric oxide production and ecNOS activity was significantly increased by apocynin treatment. Therefore, apocynin may be an effective antihypertensive drug in essential hypertension.