Ketamine in dentistry: a useful way for non-compliant pediatric patients.

The infant, like the young un-cooperative or odontophobic patient, constitute the most complex type of patient to be treated and it is frequent in modern society. The treatment of these patients is necessary to resolve the infectious-antalgic urgency and subsequently to build the patient/doctor relationship for continuing general dental care. Conscious sedation is the only way to approach this type of patient. Where therapeutic success with traditional sedation techniques is not achieved, as frequently happens in these patients, sedation with ketamine is the extreme ratio for the purpose of effective resolution of the dental problem, obviously carried out within facilities authorized for these anesthesiological modalities such as private outpatient surgery structures where, when necessary, it is possible to carry out the treatments also under general anesthesia as well as with ketamine.

Effects of the sander bite jumping appliance in patients with class ii malocclusion before growth peak.

Sander bite jumping appliance (BJA) is a functional appliance used to correct Class II malocclusion in growing patients. The aim of this study was to identify the dento-skeletal effects in patients treated with BJA before growth peak and to compare these effects with the ones obtained in a similar group treated with the Andresen activator (AA). Twenty subjects with class II relationship of the skeletal bases and cervical vertebrae maturation stage 1 or 2 were enrolled in the study and treated with BJA. This group were compared to 14 subjects treated with AA. Cephalometric analyses were carried out using landmarks derived from the analyses of Pancherz, Ricketts, Tweed and Steiner. After treatment with BJA Pg/OLp increase was 7.40±3.81 mm (P<0.001); Pg/OLp+Co/OLp significantly heightened from T0 to T1 (T0: 82.20±4.65 mm vs T1: 89.62±4.27, P<0.001). Overjet (is/OLp - ii/OLp) significantly decreased from T0 to T1 (T0: 7.40±2.31 mm vs T1: 3.05±1.34 mm, P<0.001). Molar relationship improved passing from 1.46±1.68 mm at T0 to -3.56±2.04 mm at T1 (P<0.001). No statistically significant differences were found between BJA and AA groups at T0 and T1. BJA treatment determined a Class II malocclusion correction in all patients. The correction of molar relationship was mainly due to the increase in mandibular length; the correction of the overjet was due to the increase in mandibular length, to the slight pro-inclination of the lower incisors and the mild retro-inclination of the upper incisors. No significant differences were found in effectiveness between BJA and AA.

Platelet rich plasma grafting technique combined with trans-sinusal post-extractive implants placement in the posterior maxilla: a technical report and brief literature review.

The atrophic posterior ridges are usually characterized by poor bone quality and quantity: this situation requires the use of bone regenerative techniques. Other alternative surgical approaches are investigated. Nowadays the use of trans-sinus implants offers some advantages due to its feasibility. Today, bone grafting may be practical, but depends on many factors, such as the type of bone graft used (autogenous, alloplastic, or xenograft), host response, age of the patient, various complications associated with grafting procedures, infection, and, most importantly, the time spent while the grafted material matures and is taken up by the bone. So, this case report describes the feasibility of an alternative surgical technique associated to PRP (Platelet Rich Plasma).

New trends in adjunctive treatment and diagnosis in medication-related osteonecrosis of the jaw: A 10-year review.

Medication-related osteonecrosis of the jaw (MRONJ) is a major disease under study for over the last twenty years. Different classifications have been proposed and many therapies for the different stages have been applied. The evolution of treatments lead to an increasingly conservative approach. Numerous adjuvant treatments have been proposed in the last decade. All these complementary treatments have been proposed mainly to resolve or reduce the painful stress, predominantly caused by bacterial infection, simplifying the wound healing process and improving patients' compliance. Nowadays "secondary" treatments, such as autologous platelet concentrates (APCs, more specifically PRP, PRGF or PRF), hyperbaric oxygen (HBO), Auto/tetracycline fluorescence-guided bone surgery (AF-GBS/TF-GBS), medical drugs like teriparatide or the combination between pentoxifylline and tocopherol, fluorodeoxyglucose positron emission tomography (FDG-PET), laser and/or low-laser therapy and ozone therapy are more or less well documented and known considering their clinical effectiveness. The aim of the present review is the evaluation of the quantity and quality of scientific studies concerning this specific topic.

The use of computer-guided flapless dental implant surgery (Nobel guide®) and immediate function to support a fixed full-arch prosthesis in fresh frozen homologous bone grafted patients: a retrospective cohort study with 5 to 8-year follow-up.

The introduction of computer-assisted and guided surgery has radically improved the possibility of using all available bone for implant support, reducing the need for extensive grafting procedures and allowing for better implant placement and restoration. Moreover, fresh frozen homologous bone (FFB) grafts have shown good osteoconductive properties and biocompatibility with results comparable to autologous bone patients. The purpose of this retrospective cohort study was to evaluate the survival and the success rate of implants and related fixed full arch prosthesis at the 5 to 8 years follow-up when performed with immediate function using a flapless surgical procedure and computer-aided technology (NobelGuide®, Nobel Biocare® AB, Goteborg, Sweden) in patients previously treated with FFB grafts; treated at the University of Verona with the NobelGuide® system from January 2007 to December 2012 with at least 5 years follow-up were reviewed. Survival implants and survival prosthesis' percentage reached 95% in a 5 to 8-year period. This study indicates that patients previously augmented with FFB graft for maxillary or mandibular bone atrophy can be safely treated with implant supported prosthesis based on the NobelGuide® protocol, with the aid of computer-generated guide.

The rule of hydrogen peroxide long term rinse during a particular alveolar bone healing after ONJ injuries in a patient with periodontal disease: a 4-year radiological follow up report of a mental nerve emergence migration.

Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ) is a pathology initially described in the early 2000s that has become increasingly common in clinical dentistry and maxillofacial practice due to the frequent use of bisphosphonates medical drugs (BPs) to treat various diseases such as osteoporosis, Paget's syndrome, osteomyelitis and in bone metastases secondary to tumors. Supragingival irrigation applied as monotherapy and in combination with root planning or BFs related bone necrosectomy revealed that supragingival irrigation with a variety of agents reduced the gingival microbial load and gingival inflammation. In this 4-year follow-up study we analyze the use of hydrogen peroxide (H2O2) as an antimicrobial agent for maintenance periodontal health, improving the longevity of teeth and oral cavity healing process.

Zygomatic implants supported rehabilitations in atrophic maxilla: sinus complications, radiological, periodontal and prosthodontic evaluations: a one year follow up retrospective longitudinal study.

The rehabilitation of maxillary bone atrophy represents one of the main challenges of modern oral implantology. The use of zygomatic implants in the prosthetic rehabilitation of the patient affected by severe maxillary bone atrophy is another therapeutic alternative, not exempt from complications. The present study included 19 patients with edentulous maxillae who were treated between 2013 to 2015 with at least two zygomatic implants at the Department of Maxillofacial Surgery, Verona, Italy. The purpose of this retrospective longitudinal study was to evaluate sinus complications and radiological, periodontal and prosthetic evaluations of zygomatic implants technique in severe atrophic. Implant-prosthetic rehabilitation of the upper jaw edentulous severely atrophic using zygomatic implants represents one safe and repeatable technique. In terms of implant survival from our study showed an implant CRS (common reporting standard) of 98.5% and a prosthetic CRS 100% with a mean follow-up period of 19.2 months (range). Both recorded data are superimposed on major reported studies in literature.

A randomised controlled trial of amnioexchange for fetal gastroschisis.

OBJECTIVE: Morbidity in fetuses affected by gastroschisis is mainly the result of bowel ischaemic and inflammatory processes. Experimental studies on animal models show that clearing amniotic fluid from the digestive secretions by amnioexchange procedures reduces the inflammatory process. We evaluated the benefit of the amnioexchange procedure for fetal gastroschisis in humans. DESIGN: Prospective, interventional, randomised study. SETTING: Eight referral centres for fetal medicine. POPULATION: Pregnant women carrying a fetus with gastroschisis. METHODS: We compared, in utero, amnioexchange with a sham procedure. The protocol included, in both arms, steroid injections at 30 weeks of gestation and the use of postnatal minimal enteral feeding. MAIN OUTCOME MEASURES: The primary outcome was a composite variable based on the duration of ventilation and parenteral nutrition. Secondary outcomes were the effectiveness and safety of the amnioexchange procedure, including the rate of perinatal death, time to full enteral feeding, primary closure, and late feeding disorders. RESULTS: Sixty-four patients were randomised. There was no difference in the composite criteria between the amnioexchange and control groups. Based on an intention-to-treat analysis, there were no significant between-group differences in pregnancy outcome or complications. When studying the relationship between digestive compounds and amniotic fluid inflammatory markers, a clear correlation was found between bile acid and both ferritin and interleukin 1ß (IL1ß). CONCLUSIONS: In humans, amnioexchange, as described in our protocol, is not an option for fetal care; however, we provide supplementary proof of the involvement of inflammation in the pathogenicity of gastroschisis and suggest that future research should aim at reducing inflammation. ClinicalTrials.gov: NCT00127946. TWEETABLE ABSTRACT: A prospective, interventional, randomised study shows no benefit of amnioexchange for fetal gastroschisis in humans.

Out-of-Hospital screening for HIV, HBV, HCV and Syphilis in a vulnerable population, a public health challenge.

We explored rates of Hepatitis B virus (HBV), Human Immunodeficiency Virus, Hepatitis C virus and Syphilis in a vulnerable population (mostly intravenous drug users, sex workers and homeless people) and focused on factors associated with failure to return for results (FTR) and with having a false perception (FP) of Immunization against HBV. We performed a prospective multicenter observational study in nine mobile (Out-of-Hospital) areas of screening located in Paris from 1 January 2014 through 31 December 2014. A total of 341 patients were recruited. The proportion of FTR for results was 38.75%. In multivariate analysis, unemployment was significantly associated with FTR (OR = 4.29; IC = [1.12; 16.39]), as well as having been screened in the past (OR = 4.32, IC = [1.70; 10.97]); 18.03% of patients had a FP of an Immunization against HBV. In multivariate analysis, having one's own place of residence protected against FP (OR = 0.33, [0.12; 0.95]), while being screened in the past enhanced the risk of FP (OR = 3.28, IC = [1.06; 10.11]). The rate of FTR is a problem and use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis. In addition, more information and comprehension of the results should be provided together with specific anti-HBV vaccination campaigns targeting these specific populations.

[Well-being in adulthood of patients with chronic conditions in childhood: The GEDEPAC-2 questionnaire]. / Bien-être à l'âge adulte des enfants atteints de maladies chroniques : le questionnaire GEDEPAC-2.

BACKGROUND: In France, chronic diseases affect 3 million children. In children with chronic conditions, long-term somatic outcome has been well described, but little is known about the psychosocial aspects of well-being. METHODS: Our aim was to build a self-administered questionnaire of global well-being in adults who had a chronic disease since or during childhood using a multidimensional and nonspecific approach. The questionnaire was constructed by a multidisciplinary group (epidemiologists, clinicians, sociologist, statistician). Items were built in compliance with reference data from the French general population (national surveys, free access) to allow comparative analysis adjusted for age and sex (and eventually other confounding factors) by indirect standardization (qualitative variables) or Z-scores (quantitative variables). RESULTS: The GEDEPAC-2 includes 108 items exploring 11 domains: education, employment, housing, material security, social links, civic engagement, leisure, environment, physical health/risky behavior, health-related quality of life and sex life. Factual questions and satisfaction scales jointly explore social well-being. Quality of life is analyzed in terms of physical quality of life, mental quality of life, fatigue and burden of treatment by 3 questionnaires validated in French (SF-12; MFI-20; Burden of Treatment Questionnaire). Experience of transition from pediatric to adult healthcare is described in 21 items. Paper and electronic versions were developed. CONCLUSION: Built in a multidimensional approach to well-being and in line with the available reference data, GEDEPAC-2 will facilitate the implementation of future studies on impact in adulthood of chronic disease in childhood.

Prostate cancer immunotherapy, particularly in combination with androgen deprivation or radiation treatment. Customized pharmacogenomic approaches to overcome immunotherapy cancer resistance.

Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation. Unlike afore said immune check point inhibitors, both cell-based (by the use of prostate specific antigen carriers autologous dendritic cells or even whole cancer cells) and recombinant viral vector vaccines are able to induce immune-mediated focused killing of specific antigen-presenting prostate cancer cells. Such vaccines, either used alone or concurrently/sequentially combined with above-mentioned conventional therapies, led to generally reach, in the field of various clinical trials, reasonable results particularly as regards the patient's overall survival. Adoptive trasferred T-cells, as adoptive T-cell passive immunotherapy, and monoclonal antibodies against specific antigen-endowed prostate cancer cells can improve immune micro-environmental conditions. On the basis of a preliminary survey about various immunotherapy strategies, are here also outlined their effects when combined with androgen deprivation therapy or radiation. What's more, as regard the immune-based treatment effectiveness, it has to be pointed out that suitable personalized epigenetic/gene profile-achieved pharmacogenomic approaches to target identified gene aberrations, may lead to overcome - as well as for conventional therapies - possible prostate cancer resistance to immunotherapy.

Urology pertinent neuroendocrine tumors: focusing on renal pelvis, bladder, prostate located sympathetic functional paragangliomas.

Urology pertinent neuroendocrine neoplasias are more and more driving to research attractive contributions mainly as regards the urinary tract paragangliomas, besides the prostate cancer neuroendocrine differentiation. About such visceral sympathetic paragangliomas, a considerable attention is aroused by those concerning the renal pelvis, urinary bladder and, particularly, the prostate gland. Essential catecholamine/adrenergic signal-mediated pathophysiological implications and outlined diagnostic approaches are here taken into consideration. Particularly, to reach an accurate functional diagnostic assessment, both plasma and urine catecholamine level tests are required together with ¹²³I or ¹³¹I-meta-iodobenzylguanidine (MIBG) scan while ¹³¹I-, instead of ¹²³I-, labeled MIBG, proving to be also useful to targeted radionuclide therapy of sympathetic paragangliomas. Nevertheless, a thorough diagnostic confirmation should be obtained by a proper histologic/ immunohistochemical study, so that it respectively highlighting the typical "zellballen" cell setting and neuroendocrine tumor cell specific biomarkers such as chromogranin-A, synaptophysin, neuron-specific enolase. Open/laparoscopic/robot-assisted surgical procedures are performed under α1 (doxazosin, prazosin) - and ß(propranolol)-adrenergic blockade to avoid the risk of an intraoperative adrenergic signal-triggered hypertensive crisis, what moreover may occur also during cystoscopy and biopsy in case of bladder or prostate paraganglioma. Given a conceivable likeness, about some adrenergic-mediated pathophysiological implications, between prostate paraganglioma and prostate cancer neuroendocrine transdifferentiation - although as regards two obviously different diseases - a reliable pathogenetic matter concerning prostate paraganglioma is requiring novel research approaches.

Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

Kidney transplant recipients carrying the CYP3A4*22 allelic variant have reduced tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations.

CYP3A4*22 is an allelic variant of the cytochrome P450 3A4 associated with a decreased activity. Carriers of this polymorphism may require reduced tacrolimus (Tac) doses to reach the target residual concentrations (Co). We tested this hypothesis in a population of kidney transplant recipients extracted from a multicenter, prospective and randomized study. Among the 186 kidney transplant recipients included, 9.3% (18 patients) were heterozygous for the CYP3A4*22 genotype and none were homozygous (allele frequency of 4.8%). Ten days after transplantation (3 days after starting treatment with Tac), 11% of the CYP3A4*22 carriers were within the target range of Tac Co (10-15 ng/mL), whereas among the CYP3A4*1/*1 carriers, 40% were within the target range (p = 0.02, OR = 0.19 [0.03; 0.69]). The mean Tac Co at day 10 in the CYP3A4*1/*22 group was 23.5 ng/mL (16.6-30.9) compared with 15.1 ng/mL (14-16.3) in the CYP3A4*1/*1 group, p < 0.001. The Tac Co/dose significantly depended on the CYP3A4 genotype during the follow-up (random effects model, p < 0.001) with the corresponding equivalent dose for patients heterozygous for CYP3A4*22 being 0.67 [0.54; 0.84] times the dose for CYP3A4*1/*1 carriers. In conclusion, the CYP3A4*22 allelic variant is associated with a significantly altered Tac metabolism and carriers of this polymorphism often reach supratherapeutic concentrations.

Drug-induced retroperitoneal fibrosis: short aetiopathogenetic note, from the past times of ergot-derivatives large use to currently applied bio-pharmacology.

Among the secondary forms of retroperitoneal fibrosis (RPF), that drug-induced shows very intriguing aspects given both the broad range of involved pharmaceuticals and the considerable interest arisen from the related pathogenetic mechanisms. The particular incidence, in the last four decades past century, of the RPF due to long-term use of ergot alkaloid derivatives (ergotamine, methysergide, pergolide, bromocriptine, cabergoline) and specific L-dopa derived agents, such as methyldopa, as well as to different analgesics, came progressively down given that their long-term use for either the prevention of migraine attacks or the therapy of chronic pathologies (Parkinson's disease, prolactinoma, pain management, etc) has been, year after year, supplanted or even made unavailable in many countries. More recently, instead, the occurrence of the RPF has been sometimes identified with the use of antitumoral chemotherapeutics, such as carboplatin and methotrexate, and, just lately, as an unusual side-effect of certain biological agents, about which it is timely to go into specific pathogenetic problems in more depth.

Molecularly targeted radiosensitization chances towards gene aberration-due organ confined/regionally advanced prostate cancer radioresistance.

Considering that the prostate cancer radioresistance occurs in a significant percentage--as 20-40% of prostate cancer (PCa) patients undergone external beam radiation therapy developing, within ten years, recurrent and more aggressive tumor--the resort to customized radiosensitizer measures, focusly targeting PCa radioresistance-linked individual molecular aberrations, can increase the successful outcomes of PCa radiotherapy.

Multiple health care visits related to a pediatric emergency visit for young children with common illnesses.

UNLABELLED: We aim to describe the number of health care visits before and after pediatric emergency department (PED) visits for common illnesses in a French tertiary pediatric hospital. This was a prospective cohort study with 501 children under 6 years of age who were evaluated and discharged from a tertiary care PED. Enrollment occurred on eight randomly selected study days between November 2010 and June 2011. The caregivers were then contacted via telephone 8 days later to obtain follow-up data, including information about return visits to health care facilities. Multiple visits were made by 206 (41 %) children, previous visits had occurred for 139 (28 %) children, and return visits had occurred for 94 (19 %) children. Previous and return visits were made at the PED as well as in general practitioners' offices and private pediatric offices. The median age of the subjects was 18 months. Fever was the most common complaint and was associated with more frequent multiple heath care visits. CONCLUSION: Multiple heath care visits for the same illness are frequent, especially for febrile children. Interestingly, this phenomenon concerns every type of health care facility, including the PED, general practitioners' offices, and private pediatric offices. Further studies should be performed to achieve a better understanding of this phenomenon and to test specific interventions, such as parental education and improvement of the information system.

Tissue engineering as innovative chance for organ replacement in radical tumor surgery.

BACKGROUND: Different pathological conditions such as congenital organ absence, severe organ injuries, end-stage organ failure and malignancy-related organ removal, have few effective therapeutic options a part from a whole organ transplant, that, however, often meets with a serious shortage of suitable donor organs. AIM: The purpose of this paper consists in highlighting what the novel tissue engineering approaches might help to solve such problems. EMERGING CONCEPTS: A recent approach in tissue/organ engineering, particularly to build bioartificial airways, is the procedure of decellularizing a whole donor organ to obtain a complex 3D-biomatrix-scaffold maintaining the intrinsic vascular network, that is subsequently recellularized with recipient's autologous organ-specific differentiated cells or/and stem cells, to build a potentially functional biological substitute. Such strategy has been clinically used to replace organ in trachea/broncus tumor patients. In another approach, mainly used to construct a bioartificial urinary bladder tissue, different types of either biodegradable synthetic polymers or naturally-derived matrices or even polymer/biomatrix-composite materials are used as scaffold for either cell-free or autologous cell-seeded tissue engineering procedures. So far, such technique has been mainly used to make an augmentation cystoplasty in patients with end-stage poorly compliant neuropathic bladder or in exstrophic bladder subjects. FUTURE PROSPECTS: Intriguing developments in biomaterial science, nanotechnologies, stem cell biology, and further improvements in bioreactor manufacturing will allow to generate, in the near future, tissue engineered organs that, as for structure/function so the native one-like, might represent the optimum solution to replace organs in tumor surgery.

Taxane- and epothilone-based chemotherapy: from molecule cargo cytoskeletal logistics to management of castration-resistant prostate carcinoma.

Challenges in the discovery of more potent agents to treat the castration-resistant prostate carcinoma (CRPC) reflect the frustrating condition due to development of its drug-resistance in addition to hormone-refractoriness. Although among the different CRPC therapy modalities, the chemotherapy regimens might seem conceptually outclassed as exhibiting a scant tumor cell-selectivity if compared with new molecular mechanism-based agents (so-called "smart drugs"), nevertheless, combo-therapies which combine the chemotherapeutic highly killing potential with specific mechanism-targeting products, seem to be effective antitumor measures. Thus, both microtubule (taxanes, epothilones, noscapine, Vinca-derivatives) and actin filament (pertenotoxins, cytochalasin D)-targeting agents may supply valuable outcomes in CRPC, either alone or in combination with "smart drugs" such as tyrosine- or multi-kinase receptor blockers, mTOR (mammalian target of rapamicin) inhibitors, monoclonal antibodies against various growth factor signaling receptors. Among the microtubule-inhibiting drugs, taxanes are able, by binding the tubulin, to cause polymerization and stabilization of the microtubules with following suppression of their dynamic properties at the mitotic spindle, that results in cancer cell cycle block at G2/M phase together with apoptosis. Cabazitaxel, a novel taxane-based agent, unlike other taxane compounds, exhibits low propensity for P-glycoprotein (Pgp)-mediated plasmalemmal drug efflux pump, thus, avoiding the development of taxane-resistance. Epothylones are a family of novel microtubule-targeting drugs, like taxane inhibiting microtubule dynamic behaviour at mitotic spindle and, therefore, preventing cancer cells from mitosis. Unlike docetaxel and paclitaxel, epothilones maintain their cytotoxic performance even in cancer overexpressing Pgp. Epothilone B-promoted radiosensitivity enhancement has been shown in radioresistant human prostate cancer cells, because such agent is able to delay DNA- strand break repair together with prolonging cell cycle block. To insightfully understand either microtubule or actin filament meshwork-targeting drug pharmacodynamics, functional cytoskeletal features such as cytoskeleton-related molecule cargo logistics, are preliminary taken into consideration.

Coadministration of low-dose serotonin/noradrenaline reuptake inhibitor (SNRI) duloxetine with α 2-adrenoceptor blockers to treat both female and male mild-to-moderate stress urinary incontinence (SUI).

BACKGROUND: Female urinary incontinence is a relatively common disorder affecting women in different age groups, with significant prevalence amounts of stress-related subtype (stress urinary incontinence, SUI). Various neurotransmitters/neuromodulators - particularly both the glutamatergic and GABA-ergic ones - are involved in micturition/urinary continence nerve centre-based control, where Onuf's nucleus plays an important functional role under the adiuvant serotoninergic/ noradrenergic influences. OBJECTIVES: To outline, deriving them from the literature review, the SUI therapeutic implications of SNRI (serotonin-noradrenaline reuptake inhibitors) particularly of the duloxetine, though displaying its full therapeutic dose (40 mg twice/day)-related side effects and, therefore, highlighting recent issues concerning novel drug administration modalities to avoid such adverse events. EMERGING KNOWLEDGES: Intriguing studies in SUI animal models have shown that co-administration of duloxetine low dose with α 2-adrenoceptor antagonists - given the α 2-adrenoceptor inhibition-induced enhancement of duloxetine effectiveness on the urethral rhabdospincter-can avoid the duloxetine-related adverse events though perspectively reaching, in perspective translational clinical applications, the awaited beneficial effects for women suffering from intrinsic rhabdosphincter deficiency-based mild-to-moderate SUI as well as, in men, to treat post-prostatectomy mild SUI.