Α-adrenergic Blocker Research Articles

Коррекция нарушений мочеиспускания на основании результатов комплексного уродинамического обследования

Objective of the Paper: To assess the need for a urodynamic study in a patient with a spinal injury in the early recovery period. Key points. Patient N, 16 years old, was admitted to the department of medical rehabilitation with an injury of the cervical spine, fracture of the body of C4-C5 vertebrae, compression with displacement into the spinal canal, fracture-dislocation, incomplete rupture of the spinal cord at the level of C4, C5, below are the signs cystic-atrophic changes to the level of C7. According to ultrasound data: polycystic kidney disease. The patient was examined by a neuro-urologist, was assigned to perform complete blood count, urine test, biochemical blood test, ultrasound of the kidneys and bladder before and after emptying, bacteriological urine analysis, complex urodynamic study (CUDS). According to the results of the study, the diagnosis was made: Neurogenic bladder. Detrusor asensory overactivity. Detrusor-sphincter dyssynergia. Ishuriya paradox. Polycystic kidney disease. Autonomous dysreflexia. The patient was prescribed M-anticholinergic and α1-adrenergic blocker, as well as intermittent catheterization 6 times a day. After 2 months, in order to assess urodynamics, a second consultation with a neuro-urologist and a CUDS were carried out. Against the background of the therapy, there is a positive trend, dry gaps have increased. Conclusion. Correction of a neurogenic bladder in patients with spinal cord injury is an integral part of the rehabilitation process. A multidisciplinary approach with the involvement of a urologist improves the quality of patient rehabilitation. Keywords: neurogenic bladder, overactive detrusor, detrusor-sphincter dyssynergia, spinal cord injury, correction of urinary disorders, ischuria paradoxа.

Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress.

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Systematic review and meta-analysis: α-adrenergic receptor blockers in chronic prostatitis.

Prostatitis seriously endangers the health of men. While they have been widely used in recent years, there remains a lack of systematic evaluation of the clinical efficacy of α-receptor blockers (α-RBs)/α-adrenergic receptor blockers (α-ARBs) in its treatment. Based on this, this study was developed to systematically evaluate the clinical effect of α-ARB in the treatment of prostatitis. Randomized controlled trials (RCTs) studying α-RBs or α-ARBs, placebos, or other measures to treat prostatitis were searched in Cochrane Library, PubMed, Embase, and CBM databases from establishment to December 2020. The quality of included articles was evaluated using the Cochrane System Review Manual and Jadad tools, and a meta-analysis was performed using Review Manager 5.3 software. A total of six articles meeting the requirements were found and included 450 patients. Meta-analysis showed that the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score [mean difference (MD) =-1.76, 95% confidence interval (CI): (-3.35 to -0.17), and P=0.03], pain score [MD =-2.24, 95% CI: (-3.65 to -0.83), and P=0.002], voiding symptom score [MD =-1.21, 95% CI: (-2.06 to -0.35), and P=0.006], and quality of life score [MD =-1.40, 95% CI: (-1.48 to -1.33), and P<0.00001] for patients in the experimental group were lower in contrast to those in the control group after the treatment. The use of α-ARB could significantly improve the treatment effect of patients with prostatitis and improve their quality of life.

Alpha- and beta- adrenergic receptors regulate inflammatory responses to acute and chronic sleep fragmentation in mice.

Sleep is a recuperative process, and its dysregulation has cognitive, metabolic, and immunological effects that are largely deleterious to human health. Epidemiological and empirical studies have suggested that sleep fragmentation (SF) as result of obstructive sleep apnea (OSA) and other sleep abnormalities leads to pronounced inflammatory responses, which are influenced by the sympathetic nervous system (SNS). However, the underlying molecular mechanisms contributing to SNS regulation of SF-induced inflammation are not fully understood. To assess the effects of the SNS upon inflammatory responses to SF, C57BL/6j female mice were placed in automated SF chambers with horizontally moving bars across the bottom of each cage at specified intervals to disrupt sleep. Mice were first subjected to either control (no bar movement), acute sleep fragmentation (ASF), or chronic sleep fragmentation (CSF) on a 12:12-h light/dark schedule. ASF involved a bar sweep every 120 s for 24 h, whereas CSF involved a bar sweep every 120 s for 12 h (during 12 L; resting period) over a period of 4 weeks. After exposure to these conditions, mice received an intraperitoneal injection of either phentolamine (5 mg/kg BW; an α-adrenergic receptor blocker), propranolol (5 mg/kg BW; a β-adrenergic receptor blocker), or vehicle (saline). Serum corticosterone concentration, brain and peripheral cytokine (IL1β, TNFα, and TGFβ) mRNA expression, and body mass were assessed. ASF and CSF significantly elevated serum corticosterone concentrations as well as cytokine mRNA expression levels compared with controls, and mice subjected to CSF had decreased body mass relative to controls. Mice subjected to CSF and treated with phentolamine or propranolol had a greater propensity for a decrease in cytokine gene expression compared with ASF, but effects were tissue-specific. Taken together, these results suggest that both α- and β-adrenergic receptors contribute to the SNS mediation of inflammatory responses, and adrenergic antagonists may effectively mitigate tissue-specific SF-mediated inflammation.

The reliance on α-adrenergic receptor stimuli for blood pressure regulation in the chronically hypoxaemic fetus is not dependent on post-ganglionic activation.

Chronic hypoxaemia is associated with intrauterine growth restriction (IUGR) and a predisposition to the development of hypertension in adult life. IUGR fetuses exhibit a greater reliance on α-adrenergic activation for blood pressure regulation. The fetal blood pressure response to post-ganglionic blockade is not different between control and IUGR fetuses. The decrease in mean arterial pressure is greater in the IUGR sheep fetus after α-adrenergic receptor blockade at the level of the vasculature and this is inversely related to fetal . The increased reliance that the IUGR fetus has on α-adrenergic activation for maintenance of mean arterial pressure is not a result of increased post-ganglionic sympathetic activation. Intrauterine growth restriction (IUGR) is associated with an increased risk of cardiovascular disease in adult life. Placental restriction (PR) in sheep results in chronic hypoxaemia and early onset IUGR with increased circulating plasma noradrenaline concentrations. These IUGR fetuses exhibit a greater decrease in mean arterial pressure (MAP) during α-adrenergic blockade. We aimed to determine the role of post-ganglionic sympathetic activation with respect to regulating MAP in IUGR fetal sheep. PR was induced by carunclectomy surgery prior to conception. Fetal vascular catheterization was performed at 110-126days gestational age (GA) (term, 150 days) in nine control and seven PR-IUGR fetuses. The fetal blood pressure response to both a post-ganglionic and an α-adrenergic receptor blocker was assessed at 116-120days GA and/or 129-131days GA. The effect of both post ganglionic and α-adrenergic blockade on fetal blood pressure was then compared between control and IUGR fetuses at both GAs. There was no difference in the effect of post-ganglionic blockade on MAP in control and IUGR fetal sheep at either 116-120days GA or 129-131days GA. α-adrenergic receptor blockade decreased MAP to the same extent in both control and IUGR fetuses at 116-120days GA. At 129-131days GA, the drop in MAP in response to α-adrenergic receptor blockade was greater in IUGR fetuses than controls. There was a significant inverse relationship between the drop in MAP in response to α-adrenergic receptor blockade at both GAs with fetal . Thus, the increased dependence on α-adrenergic activation for blood pressure regulation in the chronically hypoxaemic IUGR fetus is not a result of increased post-ganglionic sympathetic activation.

Piloleiomyoma Presented by Multiple Cutaneous Nodules: a Case Report

Abstract Introduction. Piloleiomyoma is a rare benign tumor which is caused by erector pili muscle and makes up 5% of all leiomyomas. They can be solitary and multiple. Multiple lesions still pose challenges for clinicians since their treatment option is very limited. Case report. We report a case of a 25-year-old male patient who had painful papules and nodules on the neck and chest for three years. Multiple red-brown papules and nodules in the skin of regio mammaria dextra and regio submandibularis on the left were seen on physical examination. Histopathological examination of punch bi-were seen on physical examination. Histopathological examination of punch biopsy sample revealed well-circumscribed nodule composed of spindle cells. The case was reported as cutaneous leiomyoma (piloleiomyoma). The patient was given 5 mg/day amlodipin and kept under control. Conclusion. The ideal treatment option for piloleiomyoma is surgical excision, but the problem with that treatment is that the lesions have tendency to recur. Medicamentous therapy plays a limited role; however, calcium-channel blockers and α-adrenergic blockers may help in palliating or eliminating associated pain through inhibition of smooth muscle contraction.

Local α1-adrenergic blockers: An alternative for sheep cervix dilation?

To facilitate transcervical artificial insemination in sheep, the effects of local treatment with α1-adrenergic receptor antagonists on cervix dilation and hemodynamics were evaluated. Ewes (n = 7) were subjected to oestrous synchronisation every 40 days and assigned to treatments in a Latin square experimental design (seven animals × seven periods) with a factorial treatment arrangement (A × B), Factors A (prazosin or tamsulosin) and B (1, 2, or 4 mg/animal). Ewes of the six treatment groups (P1, P2, P4, T1, T2, and T4) were administered α1-adrenergic receptor antagonists while those of the control group (CG) were administered only α1-adrenergic antagonist carrier agent. Distance that the transcervical catheter penetrated without cervical resistance, mean arterial pressure, and uterine artery dopplerfluxometry were evaluated before and after 30 min, 1, 2, 4, 8, and 10 h of treatment. Catheter penetration distance was greater in ewes of the T4 and P4 groups (P < 0.01), with there being a positive correlation between dose and distance (r = 0.243). The penetration distance was similar (P = 0.84) for treated groups, with the greatest penetration occurring 2, 4, and 6 h after treatment (P < 0.01). The passage into the uterine lumen was greater (P = 0.013) in ewes of the P4 (17.9 %) and T4 (19.6 %) groups. There were no effects on blood pressure or uterine blood flow (P> 0.05). These preliminary results indicate there are benefits of treatment with 4 mg/animal of tamsulosin or prazosin in catheter passage through the sheep cervix 2–6 h after administration without hemodynamic effects.

Endothelium-derived dopamine modulates EFS-induced contractions of human umbilical vessels.

Electrical field stimulation (EFS) induces contractions of both snake aorta and human umbilical cord vessels (HUCV) which were dependent on the presence of the endothelium. This study aimed to establish the nature of the mediator(s) responsible for EFS‐induced contractions in HUCV. Rings with or without endothelium from human umbilical artery (HUA) or vein (HUV) were mounted in organ bath chambers containing oxygenated, heated Krebs‐Henseleit's solution. Basal release of dopamine (DA), noradrenaline, and adrenaline was measured by LC‐MS‐MS. Cumulative concentration‐response curves were performed with dopamine in the absence and in the presence of L‐NAME or of dopamine antagonists. EFS studies were performed in the presence and absence of L‐NAME, the α‐adrenergic blockers prazosin and idazoxan, and the dopamine antagonists SCH‐23390 and haloperidol. Tyrosine hydroxylase (TH) and dopa‐decarboxylase (DDC) were studied by immunohistochemistry and fluorescence in situ hybridizations. Basal release of dopamine requires an intact endothelium in both HUA and HUV. TH and DDC are present only in the endothelium of both HUA and HUV as determined by immunohistochemistry. Dopamine induced contractions in HUA only in the presence of L‐NAME. Dopamine‐induced contractions in HUV were strongly potentiated by L‐NAME. The EFS‐induced contractions in both HUA and HUV were potentiated by L‐NAME and inhibited by the D2‐like receptor antagonist haloperidol. The α‐adrenergic antagonists prazosin and idazoxan and the D1‐like receptor antagonist SCH‐23390 had no effect on the EFS‐induced contractions of HUA and HUV. Endothelium‐derived dopamine is a major modulator of HUCV reactivity in vitro.

Brain-wide mapping of c-fos expression in the single prolonged stress model and the effects of pretreatment with ACH-000029 or prazosin

Post-traumatic stress disorder (PTSD) is a mental health condition that is triggered by a stressful event, with symptoms including exaggerated startle response, intrusive traumatic memories and nightmares. The single prolonged stress (SPS) is a multimodal stress protocol that comprises a sequential exposure to physical restraint, forced swimming, predator scent and ether anesthesia. This procedure generates behavioral and neurobiological alterations that resemble clinical findings of PTSD, and thus it is commonly used to model the disease in rodents. Here, we applied c-fos mapping to produce a comprehensive view of stress-activated brain regions in mice exposed to SPS alone or to SPS after oral pretreatment with the serotonin-noradrenaline receptor dual modulator ACH-000029 or the α1-adrenergic blocker prazosin. The SPS protocol evoked c-fos expression in several brain regions that control the stress-anxiety response, including the central and medial amygdala, the bed nucleus of the stria terminalis, the pallidum, the paraventricular hypothalamus, the intermediodorsal, paraventricular and central medial thalamic nuclei, the periaqueductal gray, the lateral habenula and the cuneiform nucleus. These effects were partially blocked by pretreatment with prazosin but completely prevented by ACH-000029. Collectively, these findings contribute to the brain-wide characterization of neural circuits involved in PTSD-related stress responses. Furthermore, the identification of brain areas regulated by ACH-000029 and prazosin revealed regions in which SPS-induced activation may depend on the combined or isolated action of the noradrenergic and serotonergic systems. Finally, the dual regulation of serotonin and α1 receptors by ACH-000029 might represent a potential pharmacotherapy that can be applied in the peri-trauma or early post-trauma period to mitigate the development of symptoms in PTSD patients.

Effect of α-adrenergic blockers silodosin in the management of distal ureteric calculus

Background: Urinary calculus disease is one of the 3 most common urological diseases. It affects about 12% of the world population and has become a worldwide health problem. Of all the urinary tract stones 20% are ureteral stones, of which 70% are found in the distal ureter. The objective of the study is to study the effect of silodosin in the passage of calculi in the distal ureter compared to non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium) and oral fluids.Methods: This study included a total of 90 patients between the study period from October 2016 to October 2018. 45 patients were chosen randomly and advised to take plenty of oral fluids and treated with NSAIDs and the other 45 patients were treated with silodosin 8 mg HS for one month along with oral fluids and NSAIDs. After 1 month if the stone was passed successfully, it was confirmed with ultrasonography, if failed, advised for surgery.Results: Majority of the patients were in the age group of 20-45 yrs. The mean size of the calculus was 5.60 cm on the right side and 5.71 cm on the left side. Out of the 45 patients who were on treatment with silodosin 35 patients had passed the calculi and 10 patients had no results with a success rate of 77.7%. In the 45 patients who were not on silodosin, 8 patients passed the calculi and 37 patients did not pass the calculi. 21 patients among the 45 underwent urethrorenoscopy.Conclusions: Silodosin is an effective and safe drug in the management of calculi in the distal ureter.

Efficacy of α-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial.

ContextPretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).ObjectiveTo determine which type of α-adrenergic receptor blocker provides the best efficacy.DesignRandomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898)SettingMulticenter study including 9 centers in The Netherlands.Patients134 patients with nonmetastatic PPGL.InterventionPhenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized.Main Outcome MeasuresPrimary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score.ResultsMedian cumulative time outside blood pressure targets was 11.1% (interquartile range [IQR]: 4.3–20.6] in the phenoxybenzamine group compared to 12.2% (5.3–20.2)] in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8–58.0) and 50.0 (35.3–63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days.ConclusionsThe duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.

The influence of adrenergic blockade in rats with apical periodontitis under chronic stress conditions

ObjectiveTo investigate the influence of chronic stress and adrenergic blockade in a rat model of apical periodontitis. MethodsThirty-two Wistar rats were submitted to an animal model of periapical lesion and randomly divided into 4 groups (n = 8): no stress (NS); stress + saline solution (SS); stress + β-adrenergic blocker (Sβ); stress + α-adrenergic blocker (Sα). The SS, Sβ and Sα groups were submitted to an animal model of chronic stress for 28 days and received daily injections of saline solution, propranolol (β adrenergic blocker) and phentolamine (α adrenergic blocker), respectively. After 28 days the animals were euthanized and the following analyses were carried out: a) serum corticosterone levels through Radioimmunoassay; b) measurement of serum levels of IL-1B, IL-6, IL-10 and IL-17 by enzyme-linked immunosorbent assay (ELISA); c) volume of periapical bone resorption by micro-computed tomography; d) histomorphometric analysis by staining with hematoxylin and eosin; e) expression of β-AR, α-AR, receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) by immunohistochemistry; f) tartrate-resistant acid phosphatase (TRAP) staining; g) ex-vivo cytokine release followed by the stimulation with LPS in superfusion system, by ELISA. ResultsSS group displayed significantly higher corticosterone levels than NS group (non-stressed). Higher IL-1β serum level was observed in the NS group (p < .05); compared to all stressed groups. Other cytokines were present in similar amounts in the serum of all groups. All groups presented similar periapical lesions. All groups presented moderate inflammatory infiltrate, without statistically significant differences between them. No differences were observed regarding β-AR, α-AR, Rank-L and OPG expression. The number of TRAP-positive cells was significantly decreased in the groups that received daily injections of adrenergic blockers. The IL-1β release followed LPS stimulation was significantly suppressed when the superfusion media contained propranolol (p < .05). Perfusion containing phentolamine induced a greater release of IL-10. TGF-β was significantly suppressed by phentolamine perfusion in the NS group (p < .05). ConclusionsChronic stress can significantly change the inflammatory cytokines release. Rank-L/OPG system and periapical lesion volume were not affected following the current method applied. The administration of adrenergic blockers was not able to modulate the inflammatory response but presented effectivity in reducing the number of osteoclasts in the periapical region.

Urology Residency Directors' Awareness of Association between α-Adrenergic Antagonists and Floppy Iris Syndrome and Practice Patterns Regarding Prophylactic α-Adrenergic Antagonists

Purpose The use of prophylactic α-adrenergic receptor antagonists prior to surgery is associated with reduced postoperative urinary retention. However, α-adrenergic receptor antagonists have been associated with intraoperative floppy iris syndrome (IFIS). Studies have shown that IFIS is correlated with higher rates of cataract surgery complications. The purpose of this study is to investigate United States urology residency program directors' (1) awareness of the association between α-adrenergic receptor antagonists and IFIS and (2) practice patterns regarding the use of prophylactic α-adrenergic receptor antagonists prior to surgery. Materials and Methods An anonymous, online survey was sent to the program director of each of the 138 urology residency programs accredited by the Accreditation Council for Graduate Medical Education. The survey assessed program directors' knowledge regarding the association between α-adrenergic receptor antagonists and IFIS, and practice patterns regarding the use of prophylactic α-adrenergic receptor antagonists prior to surgery. Results Sixty-nine of the 138 (50%) residency directors responded. Forty percent of respondents believe that tamsulosin (Flomax) does not increase the risk of IFIS. Fifty-two percent of respondents prescribe or consider prescribing prophylactic α-adrenergic blockers prior to surgery, with tamsulosin being the most preferred α-adrenergic blocking agent. Of the prescribing urologists, only 58% counsel most of their patients regarding the association between the prescribed drug and IFIS, 28% never ask patients whether they have had cataract surgery, and 56% would change the drug or dosage used if they learned that a patient had not yet had cataract surgery. Conclusion The results of this study demonstrate the potential to decrease the risk of IFIS through education of urologists regarding the association of α-adrenergic antagonists with IFIS.

Dual Effect of Doxazosin: Anticancer Activity on SH-SY5Y Neuroblastoma Cells and Neuroprotection on an In Vitro Model of Alzheimer's Disease

Several studies have demonstrated the antitumor effect of doxazosin, an α1-adrenergic blocker, against glioma and breast, bladder and prostate cancers. Doxazosin is also being evaluated as a treatment for posttraumatic stress disorder (PTSD) and alcoholism, and α1-adrenergic blockers have been linked to neuroprotection in neurodegenerative disorders, such as Alzheimer's Disease (AD). Cancer and AD have an inverse relationship in many aspects, with several factors that contribute to apoptosis inhibition and proliferation being increased in cancers but decreased in AD. Neuroblastoma (NB) is a pediatric tumor derived from embryonic neural-crest cells, with an overall cure rate of 40%, despite aggressive treatment. Thus, due to the need of new therapeutic strategies against NB and neurodegenerative disorders and the inverse relationship between these diseases, we investigated whether doxazosin may serve as an antitumor and neuroprotective agent. We analyzed the drug's effects on undifferentiated and retinoic acid-differentiated SH-SY5Y human NB cells and on an in vitro model of organotypic hippocampal cultures exposed to amyloid-β. Doxazosin showed antitumor effect on undifferentiated NB cells by induction of apoptosis, necrosis, cell cycle arrest and decrease of p-EGFRTyr1048 levels. On differentiated cells, doxazosin was less cytotoxic and increased p-EGFRTyr1048, p-AktSer473 and p-GSK-3βSer9 levels. Moreover, the drug was able to protect hippocampal slices from amyloid-β toxicity through prevention of GSK-3β activation and of Tau hyperphosphorylation. Therefore, our results show that doxazosin has antitumor activity against undifferentiated NB and is neuroprotective on an in vitro model of Alzheimer's disease.

38] Efficacy of silodosin on the outcome of semi-rigid ureteroscopy for management of large distal ureteric calculi: single-blinded placebo-controlled randomised trial

ObjectiveTo evaluate the efficacy of administration of silodosin, as a new α-adrenergic blocker (AAB), on the success rate of semi-rigid ureteroscopy (URS) for the management of large distal ureteric stones.

Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones

Urinary stone disease is a common presentation in the emergency department, and α-adrenergic receptor blockers, such as tamsulosin, are commonly used to facilitate stone passage. To determine if tamsulosin promotes the passage of urinary stones within 28 days among emergency department patients. We conducted a double-blind, placebo-controlled clinical trial from 2008 to 2009 (first phase) and then from 2012 to 2016 (second phase). Participants were followed for 90 days. The first phase was conducted at a single US emergency department; the second phase was conducted at 6 US emergency departments. Adult patients were eligible to participate if they presented with a symptomatic urinary stone in the ureter less than 9 mm in diameter, as demonstrated on computed tomography. Participants were randomized to treatment with either tamsulosin, 0.4 mg, or matching placebo daily for 28 days. The primary outcome was stone passage based on visualization or capture by the study participant by day 28. Secondary outcomes included crossover to open-label tamsulosin, time to stone passage, return to work, use of analgesic medication, hospitalization, surgical intervention, and repeated emergency department visit for urinary stones. The mean age of 512 participants randomized to tamsulosin or placebo was 40.6 years (range, 18-74 years), 139 (27.1%) were female, and 110 (22.8%) were nonwhite. The mean (SD) diameter of the urinary stones was 3.8 (1.4) mm. Four hundred ninety-seven patients were evaluated for the primary outcome. Stone passage rates were 50% in the tamsulosin group and 47% in the placebo group (relative risk, 1.05; 95.8% CI, 0.87-1.27; P = .60), a nonsignificant difference. None of the secondary outcomes were significantly different. All analyses were performed according to the intention-to-treat principle, although patients lost to follow-up before stone passage were excluded from the analysis of final outcome. Tamsulosin did not significantly increase the stone passage rate compared with placebo. Our findings do not support the use of tamsulosin for symptomatic urinary stones smaller than 9 mm. Guidelines for medical expulsive therapy for urinary stones may need to be revised. ClinicalTrials.gov Identifier: NCT00382265.

Laboratory practical to study the differential innervation pathways of urinary tract smooth muscle.

In the mammalian lower urinary tract, there is a reciprocal relationship between the contractile state of the bladder and urethra. As the bladder fills with urine, it remains relaxed to accommodate increases in volume, while the urethra remains contracted to prevent leakage of urine from the bladder to the exterior. Disruptions to the normal contractile state of the bladder and urethra can lead to abnormal micturition patterns and urinary incontinence. While both the bladder and urethra are smooth-muscle organs, they are differentially contracted by input from cholinergic and sympathetic nerves, respectively. The laboratory practical described here provides an experiential approach to understanding the anatomy of the lower urinary tract. Several key factors in urinary tract physiology are outlined, e.g., the bladder is contracted by activation of the parasympathetic pathway via cholinergic stimulation on muscarinic receptors, whereas the urethra is contracted by activation of the sympathetic pathway via adrenergic stimulation on α1-adrenoceptors. This is achieved by measuring the force generated by bladder and urethra smooth muscle to demonstrate that acetylcholine contracts the smooth muscle of the bladder, whereas adrenergic agonists contract the urethral smooth muscle. An inhibition of these effects is also demonstrated by application of the muscarinic receptor antagonist atropine and the α1-adrenergic receptor blocker phentolamine. A list of suggested techniques and exam questions to evaluate student understanding on this topic is also provided.

Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats

Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α1-adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, α1-adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, α1/α2-adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α2-adrenoceptors are not under stimulation, but not in the other vascular beds investigated.

Genetic variants in 5p13.2 and 7q21.1 are associated with treatment for benign prostatic hyperplasia with the α-adrenergic receptor antagonist

Background: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment.Methods: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment.Results: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p = .01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p = .0388) and rs4646437 in CYP3A4 at 7q21.1 (p = .0325), associated with drug effect. (4) Allele “G” for rs16902947 was found to be risk alleles for BPH risk (OR= 2.357, 95%CI 1.01–1.48). The “A” allele of rs4646437 was associated with lower IPSS at baseline (β= −0.4232, p= .03255).Conclusions: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

THE EFFECT OF COMBINED α1-ADRENERGIC BLOCKERS AND PDE-5 INHIBITORS THERAPY ON IPSS, IIEF-5, QMAX AND PVR PATIENTS BPH WITH LUTS AND ERECTILE DYSFUNCTION

Purpose: Assess the efficacy of combined α1-adrenergic blocker (tamsulosin 0,4 mg) and PDE5 inhibitor (tadalafil 5 mg) therapy compared to tadalafil or tamsulosin alone in treating patient BPH with LUTS and ED. Material and methods: A randomised, double blind experimental study assessed 36 sexually active men with ED and LUTS suggestive of BPH. All patients were randomized to 3 groups: tamsulosin 0,4 mg (n=12), tadalafil 5mg (n=12), and combination of tamsulosin 0,4 mg and tadalafil 5 mg (n= 12), once daily for 6 weeks. Changed in IPSS scores and QoL index, IIEF-5 scores, Qmax, PVR and blood pressure were assessed and compared to baseline. Complication and serious adverse event were also monitored. Outcomes were assessed using ranked analysis of variance (ANOVA) and Kruskall-Wallis depends on data distribution and homogenity.Results: Tamsulosin 0,4 mg once daily for 6 weeks were significantly improved IPSS score and QoL index and Qmax from baseline. Tadalafil 5 mg once daily for 6 weeks were significantly improved IPSS score, QoL index and IIEF-5 index from baseline. Combined tamsulosin and tadalafil therapy were significantly improved IPSS score, QoL index, IIEF-5 index and Qmax from baseline. Significantly better improvement on IIEF-5 dan Qmax from baseline were observed on the combination of tamsulosin and tadalafil compared to monotherapy with tamsulosin or tadalafil after 6 weeks in patients BPH with LUTS and erectile dysfunction. There was no significant decreased in systolic and diastolic blood pressure from combined treatment compared to single treatment.Conclusions: Combined tamsulosin and tadalafil therapy was significantly better in improving IIEF aObjective: Assess the efficacy of combined α1-adrenergic blocker (tamsulosin 0.4 mg) and PDE5 inhibitor (tadalafil 5 mg) therapy compared to tadalafil or tamsulosin alone in treating patient Benign Prostate Hyperplasia (BPH) with lower urinary tract symptom (LUTS) and erectile dysfunction (ED). Material &amp; methods: A randomised, double blind experimental study assessed 36 sexually active men with ED and LUTS suggestive of BPH. All patients were randomized to 3 groups: tamsulosin 0.4 mg (n=12), tadalafil 5mg (n=12), and combination of tamsulosin 0.4 mg and tadalafil 5 mg (n= 12), once daily for 6 weeks. Changed in IPSS scores and QoL index, IIEF-5 scores, Qmax, PVR and blood pressure were assessed and compared to baseline. Complication and serious adverse event were also monitored. Outcomes were assessed using ranked analysis of variance (ANOVA) and Kruskall-Wallis depends on data distribution and homogenity. Results: Tamsulosin 0.4 mg once daily for 6 weeks were significantly improved IPSS score, QoL index and Qmax from baseline. Tadalafil 5 mg once daily for 6 weeks were significantly improved IPSS score, QoL index and IIEF-5 index from baseline. Combined tamsulosin and tadalafil therapy were significantly improved IPSS score, QoL index, IIEF-5 index and Qmax from baseline. Significantly better improvement on IIEF-5 dan Qmax from baseline were observed on the combination of tamsulosin and tadalafil compared to monotherapy with tamsulosin or tadalafil after 6 weeks in patients BPH with LUTS and erectile dysfunction. There was no significant decreased in systolic and diastolic blood pressure from combined treatment compared to single treatment. Conclusion: Combined tamsulosin and tadalafil therapy was significantly better in improving IIEF and Qmax, but not significantly better in improving IPSS and PVR compared to monotherapy with tamsulosin or tadalafil alone. Combined therapy was well tolerated without serious adverse effect.nd Qmax, but not significantly better in improving IPSS and PVR compared to monotherapy with tamsulosin or tadalafil alone. Combined therapy was well tolerated without serious adverse effect.