Non-antibacterial methods for the prevention and treatment of recurrent lower urinary tract infections

Urinary tract infections are widespread throughout the world and occupy one of the leading places among infectious diseases. Antibacterial methods are the basis of modern treatment standards. At the same time, a widespread increase in antibiotic resistance of the main uropathogens is currently observed. In clinical practice, recurrent lower urinary tract infections are increasingly common. Following this, the main task of the doctor is to maximize the recurrence-free interval. Given the obvious negative collateral effect of long-term antibiotic prophylaxis, specialists are increasingly turning to alternative methods. Non-antibacterial preventive measures are aimed at key links in the pathogenesis of the disease, such as counteracting the penetration and adhesion of uropathogens, as well as stimulating the immune system of the macroorganism. The available physicians' toolkit includes pharmacological agents (d-mannose, methenamine hippurate, estrogens, non-steroidal anti-inflammatory drugs, probiotics, intravesical glycosaminoglycans, immunostimulants and vaccines), natural uroantiseptics (medicinal herbs and cranberry products), as well as behavioural therapy. The main advantages of non-antibacterial methods for the treatment and prevention of lower urinary tract infections are environmental friendliness. It is associated with the absence of a negative effect on the commensal flora, as well as a reduction in the risk of developing antibiotic resistance. The current guidelines provide very limited information on the application of this approach to treatment. Published studies indicate the high potential of non-antibacterial methods, some of which are comparable in effectiveness to standard therapy. However, the quality of studies and the lack of drug use standards do not allow including this approach in the existing guidelines. The need for new, high-quality clinical trials is evident

Possibilities of peripheral magnetic neuromodulation in the treatment of lower urinary tract symptoms in men

Introduction. Lower urinary tract symptoms (LUTS) are common in men and are associated with a significant decrease in quality of life. To date, there is no universal approach to the treatment of LUTS, which determines the need to search for new methods for influencing the lower urinary tract.Purpose of the study. To test the hypothesis that the use of peripheral magnetic neuromodulation (PMN) in male patients with LUTS will reduce the severity of LUTS.Materials and methods. Sixty-eight men with LUTS were enrolled in a prospective, randomized study. Patients were randomized in a 1:1 ratio for PMN or drug therapy with an alpha-1-blocker (tamsulosin). The primary endpoint was a reduction the LUTS severity such as urinary frequency during the day, nocturia and urgency as assessed using the IPSS questionnaire and urination diary. Improvements in urodynamic parameters such as maximum urine flow rate (Q max), mean urine flow rate (Q ave), and residual urine volume (PVR) were the secondary endpoint of the study. The results were evaluated on equal terms (10 days and 1 month) in both groups.Results. Sixty-seven (98.5%) subjects were included in the final base. Ten days after the start of therapy in the magnetic stimulation group, symptom relief was noted by 21 people (61.7%), the mean IPSS score showed a decrease from 18.1 ± 2.1 to 16.9 ± 3.2 points (p = 0.037). The number of urinations per day decreased from 14 (6 - 20) to 10 (6 - 14) times (p < 0.001). Objective indicators of urodynamics did not change in both groups. At a period of 1 month, PMN occurred in 22 (64.7%) patients, the IPSS score was 16.6 ± 3.7 points (p = 0.032), the number of urinations 9 (6 - 14) times (p < 0.001). Objective indicators have not changed. In the tamsulosin group, IPSS score changed from 19.27 ± 5.08 to 15.4 ± 4.85 (p < 0.001), Q max 14.36 ± 2.82 ml/s increased to 15.94 ± 2.71 ml/s (p = 0.032), while the Q ave did not change (p = 0.17). The number of urinations decreased from 13 (6 - 19) times to 10 (6 - 14) times (p <0.001).Conclusion. The study demonstrated the promise of PMN in men with LUTS in terms of improving the quality of life. The proposed method may be preferable for patients dissatisfied with drug therapy. Further placebo-controlled studies are required to help determine the role of PMN in the management of patients with LUTS

A dynamical approach to the spatiotemporal aspects of the Portevin-Le Chatelier effect: Chaos,turbulence and band propagation

Experimental time series obtained from single and poly-crystals subjected to a constant strain rate tests report an intriguing dynamical crossover from a low dimensional chaotic state at medium strain rates to an infinite dimensional power law state of stress drops at high strain rates. We present results of an extensive study of all aspects of the PLC effect within the context a model that reproduces this crossover. A study of the distribution of the Lyapunov exponents as a function of strain rate shows that it changes from a small set of positive exponents in the chaotic regime to a dense set of null exponents in the scaling regime. As the latter feature is similar to the GOY shell model for turbulence, we compare our results with the GOY model. Interestingly, the null exponents in our model themselves obey a power law. The configuration of dislocations is visualized through the slow manifold analysis. This shows that while a large proportion of dislocations are in the pinned state in the chaotic regime, most of them are at the threshold of unpinning in the scaling regime. The model qualitatively reproduces the different types of deformation bands seen in experiments. At high strain rates where propagating bands are seen, the model equations are reduced to the Fisher-Kolmogorov equation for propagative fronts. This shows that the velocity of the bands varies linearly with the strain rate and inversely with the dislocation density, consistent with the known experimental results. Thus, this simple dynamical model captures the complex spatio-temporal features of the PLC effect.Comment: 17 pages, 18 figure

High order amplitude equation for steps on creep curve

We consider a model proposed by one of the authors for a type of plastic instability found in creep experiments which reproduces a number of experimentally observed features. The model consists of three coupled non-linear differential equations describing the evolution of three types of dislocations. The transition to the instability has been shown to be via Hopf bifurcation leading to limit cycle solutions with respect to physically relevant drive parameters. Here we use reductive perturbative method to extract an amplitude equation of up to seventh order to obtain an approximate analytic expression for the order parameter. The analysis also enables us to obtain the bifurcation (phase) diagram of the instability. We find that while supercritical bifurcation dominates the major part of the instability region, subcritical bifurcation gradually takes over at one end of the region. These results are compared with the known experimental results. Approximate analytic expressions for the limit cycles for different types of bifurcations are shown to agree with their corresponding numerical solutions of the equations describing the model. The analysis also shows that high order nonlinearities are important in the problem. This approach further allows us to map the theoretical parameters to the experimentally observed macroscopic quantities.Comment: LaTex file and eps figures; Communicated to Phys. Rev.

Сomparison of biomechanical properties of non-absorbable and partially absorbable mesh implants used in surgery for urinary incontinence and genital prolapse: experimental study

Introduction. The amount of non-absorbable synthetic material used in the surgical treatment of pelvic organ prolapse and stress urinary incontinence has been shown to directly correlate with the risks of mesh-associated complications. Previously, we developed a partially absorbable implant. Currently, there are insufficient data on the use of partially absorbable implants in female pelvic floor reconstruction, which requires comparative biomechanical and pathomorphological studies.Objective. To compare the biomechanical properties of a new generation partially absorbable implants and nonabsorbable polypropylene mesh implants during animal model.Materials & methods. Thirty-nine rabbits weighing 3200 ± 250 g were randomised into three groups depending on the implanted endoprosthesis: group 1 (n = 15) — “Axilen” implant (polydioxanone 98%, polypropylene 2%), group 2 (n = 15) — “Axilen Rapid” implant (polyglycapron 98%, polypropylene 2%), group 3 (n = 9) — “Urosling 1” implant. After implantation, rabbits of all 3 groups were divided into 3 subgroups according to the withdrawal period from the experiment: 14 days, 60 days, and 180 days. The biomaterial obtained was subjected to two studies: evaluation of the macroscopic view of the explanted mesh endoprosthesis with the formed capsule and the surrounding tissues, study of the biomechanical properties of the formed connective tissue capsule with the implant.Results. According to macroscopic evaluation, there was a less significant tissue reaction to partially absorbed implants. A comparative analysis of biomechanical indices revealed no statistically significant difference in rupture elongation at all follow-up periods among the presented groups. Tensile strength, at 60 and 180 days, was not statistically different between the groups described. At 14 days, there was a statistically significant difference in tensile strength between groups 1 and 3 (p = 0.003).Conclusion. During biomechanical animal experiments, the connective tissue capsule formed on the partially absorbable implant was not inferior to the similar parameter of the non-absorbable sample in its tensile strength, which explains a great potential for the use of partially absorbable implants in reconstructive surgery of pelvic organ prolapse and stress urinary incontinence

New-generation synthetic implants for the surgical correction of pelvic organ prolapse and stress urinary incontinence: design and testing

Introduction. Up to 50.0% of postpartum women experience stress urinary incontinence (SUI) and pelvic organ prolapse (POP). One of the most common and pathogenetically substantiated methods for surgical correction of severe SIU and POP is prosthetic reconstruction of the pelvic floor, involves the use of monofilament polypropylene surgical meshes through vaginal or laparoscopic access.. However, this way is associated with specific problems, i.e., primarily mucosal erosions, and pelvic pain. This has served as a trigger for the development of new materials that reduce the likelihood of such side effects.Objective. To develop the new-generation synthetic implants for surgical correction of stress urinary incontinence and pelvic organ prolapse.Materials and methods. The main development stages: 1. design of an experimental sample of a synthetic implant (evaluation of basic, physical and mechanical properties). 2. test of an experimental sample obtained in vitro.Results. A bioresorbable polypropylene ligature delivery system was developed and manufactured in two variants: for the POP correction (mesh tape with a width of 13 – 15 mm) and for the SUI correction (mesh tape with a width of 10 – 11 mm).Conclusion. Based on the results of the in vitro tests, we can conclude that the synthetic implants developed are able to provide physiological longitudinal (axial) support of the necessary pelvic floor sections and reduce the risk of postoperative complications. Further in vivo studies are required to assess the response of living tissue to the implantation of this type of synthetic implants

Effects of crack tip geometry on dislocation emission and cleavage: A possible path to enhanced ductility

We present a systematic study of the effect of crack blunting on subsequent crack propagation and dislocation emission. We show that the stress intensity factor required to propagate the crack is increased as the crack is blunted by up to thirteen atomic layers, but only by a relatively modest amount for a crack with a sharp 60$^\circ$ corner. The effect of the blunting is far less than would be expected from a smoothly blunted crack; the sharp corners preserve the stress concentration, reducing the effect of the blunting. However, for some material parameters blunting changes the preferred deformation mode from brittle cleavage to dislocation emission. In such materials, the absorption of preexisting dislocations by the crack tip can cause the crack tip to be locally arrested, causing a significant increase in the microscopic toughness of the crack tip. Continuum plasticity models have shown that even a moderate increase in the microscopic toughness can lead to an increase in the macroscopic fracture toughness of the material by several orders of magnitude. We thus propose an atomic-scale mechanism at the crack tip, that ultimately may lead to a high fracture toughness in some materials where a sharp crack would seem to be able to propagate in a brittle manner. Results for blunt cracks loaded in mode II are also presented.Comment: 12 pages, REVTeX using epsfig.sty. 13 PostScript figures. Final version to appear in Phys. Rev. B. Main changes: Discussion slightly shortened, one figure remove

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Acute cholecystitis – early laparoskopic surgery versus antibiotic therapy and delayed elective cholecystectomy: ACDC-study

<p>Abstract</p> <p>Background</p> <p>Acute cholecystitis occurs frequently in the elderly and in patients with gall stones. Most cases of severe or recurrent cholecystitis eventually require surgery, usually laparoscopic cholecystectomy in the Western World. It is unclear whether an initial, conservative approach with antibiotic and symptomatic therapy followed by delayed elective surgery would result in better morbidity and outcome than immediate surgery. At present, treatment is generally determined by whether the patient first sees a surgeon or a gastroenterologist. We wish to investigate whether both approaches are equivalent. The primary endpoint is the morbidity until day 75 after inclusion into the study.</p> <p>Design</p> <p>A multicenter, prospective, randomized non-blinded study to compare treatment outcome, complications and 75-day morbidity in patients with acute cholecystitis randomized to laparoscopic cholecystectomy within 24 hours of symptom onset or antibiotic treatment with moxifloxacin and subsequent elective cholecystectomy. For consistency in both arms moxifloxacin, a fluorquinolone with broad spectrum of activity and high bile concentration is used as antibiotic. Duration: October 2006 – November 2008</p> <p>Organisation/Responsibility</p> <p>The trial was planned and is being conducted and analysed by the Departments of Gastroenterology and General Surgery at the University Hospital of Heidelberg according to the ethical, regulatory and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and the Good Clinical Practice guideline (GCP).</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00447304</p

Dialysis delivery of an adenosine A 2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep

In vivo microdialysis in C57BL/6J (B6) mouse was used to test the hypothesis that activating adenosine A 2A receptors in the pontine reticular formation (PRF) increases acetylcholine (ACh) release and rapid eye movement (REM) sleep. Eight concentrations of the adenosine A 2A receptor agonist 2- p- (2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; CGS) were delivered to the PRF and ACh in the PRF was quantified. ACh release was significantly increased by dialysis with 3 μm CGS and significantly decreased by dialysis with 10 and 100 μm CGS. Co-administration of the adenosine A 2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 30 nm) blocked the CGS-induced increase in ACh release. In a second series of experiments, CGS (3 μm) was delivered by dialysis to the PRF for 2 h while recording sleep and wakefulness. CGS significantly decreased time in wakefulness (−51% in h 1; −54% in h 2), increased time in non-rapid eye movement (NREM) sleep (90% in h 1; 151% in h 2), and increased both time in REM sleep (331% in h 2) and the number of REM sleep episodes (488% in h 2). The enhancement of REM sleep is consistent with the interpretation that adenosine A 2A receptors in the PRF of the B6 mouse contribute to REM sleep regulation, in part, by increasing ACh release in the PRF. A 2A receptor activation may promote NREM sleep via GABAergic inhibition of arousal promoting neurons in the PRF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66018/1/j.1471-4159.2006.03700.x.pd