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Antibiotics (Basel, Switzerland) Nov 2022is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. utilizes several interplayed systems to regulate its...
is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, could sense the adrenergic hormones in the surroundings that enhance its virulence. The current study aimed to evaluate the ability of α-adrenoreceptor antagonist prazosin to mitigate the virulence of serovar Typhimurium. The prazosin effect on biofilm formation and the expression of , , , and T3SS-type II encoding genes was evaluated. Furthermore, the prazosin intracellular replication inside macrophage and anti-virulence activity was evaluated in vivo against . . The current finding showed a marked prazosin ability to compete on SdiA and QseC and downregulate their encoding genes. Prazosin significantly downregulated the virulence factors encoding genes and diminished the biofilm formation, intracellular replication inside macrophages, and in vivo protected mice. To sum up, prazosin showed significant inhibitory activities against QS, T3SS, and bacterial espionage, which documents its considered anti-virulence activities.
PubMed: 36358239
DOI: 10.3390/antibiotics11111585 -
Molecular Pain 2021Neuropeptide W (NPW) messenger ribonucleic acid (mRNA) and NPBW1 and/or NPBW2 mRNA are expressed in the descending pain inhibitory system. In the present study, we...
Neuropeptide W (NPW) messenger ribonucleic acid (mRNA) and NPBW1 and/or NPBW2 mRNA are expressed in the descending pain inhibitory system. In the present study, we examined whether NPW microinjected into the descending pain inhibitory system, such as the periaqueductal gray (PAG), locus coeruleus (LC), and rostral ventromedial medulla (RVM), produces an analgesic effect using a rat formalin test. Microinjections of NPW into the PAG ipsilateral and contralateral to the formalin-injected side, LC ipsilateral and contralateral to the formalin-injected side, and RVM produced an analgesic effect. In the RVM study, the analgesic effect was antagonized by WAY100135, a 5-HT antagonist, and enhanced by prazosin, an α1 antagonist, and SB269970, a 5-HT antagonist. Naloxone, an opioid antagonist, also antagonized the effect of NPW in the RVM study. In the ipsilateral LC study, the analgesic effect was antagonized by WAY100135, idazoxan, an α2 antagonist, and naloxone and was enhanced by prazosin and SB269970. In the contralateral LC study, the analgesic effect was antagonized by prazosin, idazoxan, SB269970, and naloxone. The analgesic effect was antagonized by WAY100135, SB269970, idazoxan, and naloxone in the ipsilateral and contralateral PAG studies. These findings strongly suggest that NPBW1/W2 activation by NPW microinjection into the RVM, LC, and PAG affect the descending pain modulatory system and produce anti-nociceptive and pro-nociceptive effects in the rat formalin test.
Topics: Analgesics; Animals; Formaldehyde; Injections; Ligands; Locus Coeruleus; Male; Medulla Oblongata; Neuropeptides; Pain; Periaqueductal Gray; Rats, Sprague-Dawley; Receptors, Neuropeptide; Rats
PubMed: 33573476
DOI: 10.1177/1744806921992187 -
PloS One 2016Glucocorticoids (GC) elicit skeletal muscle capillary rarefaction, which can subsequently impair blood distribution and muscle function; however, the mechanisms have not...
Glucocorticoids (GC) elicit skeletal muscle capillary rarefaction, which can subsequently impair blood distribution and muscle function; however, the mechanisms have not been established. We hypothesized that CORT would inhibit endothelial cell survival signals but that treatment with the alpha-1 adrenergic receptor inhibitor prazosin, which leads to angiogenesis in skeletal muscle of healthy rats, would reverse these effects and induce angiogenesis within the skeletal muscle of corticosterone (CORT)-treated rats. Male Sprague Dawley rats were implanted subcutaneously with CORT pellets (400 mg/rat), with or without concurrent prazosin treatment (50mg/L in drinking water), for 1 or 2 weeks. Skeletal muscle capillary rarefaction, as indicated by a significant reduction in capillary-to-fiber ratio (C:F), occurred after 2 weeks of CORT treatment. Concurrent prazosin administration prevented this capillary rarefaction in CORT-treated animals but did not induce angiogenesis or arteriogenesis as was observed with prazosin treatment in control rats. CORT treatment reduced the mRNA level of Angiopoietin-1 (Ang-1), which was partially offset in the muscles of rats that received 2 weeks of co-treatment with prazosin. In 2W CORT animals, prazosin treatment elicited a significant increase in vascular endothelial growth factor-A (VEGF-A) mRNA and protein. Conversely prazosin did not rescue CORT-induced reductions in transforming growth factor beta-1 (TGFβ1 and matrix metalloproteinase-2 (MMP-2) mRNA. To determine if CORT impaired shear stress dependent signaling, cultured rat skeletal muscle endothelial cells were pre-treated with CORT (600nM) for 48 hours, then exposed to 15 dynes/cm2 shear stress or maintained with no flow. CORT blunted the shear stress-induced increase in pSer473 Akt, while pThr308 Akt, ERK1/2 and p38 phosphorylation and nitric oxide (NO) production were unaffected. This study demonstrates that GC-mediated capillary rarefaction is associated with a reduction in Ang-1 mRNA within the skeletal muscle microenvironment and that concurrent prazosin treatment effectively increases VEGF-A levels and prevents capillary loss.
Topics: Angiogenesis Inducing Agents; Angiopoietin-1; Animals; Biomarkers; Capillaries; Endothelial Cells; Gene Expression; Glucocorticoids; Male; Mice; Models, Animal; Muscle, Skeletal; Myoblasts; Prazosin; Protective Agents; Rats; Stress, Mechanical; Thrombospondin 1; Vascular Endothelial Growth Factor A
PubMed: 27861620
DOI: 10.1371/journal.pone.0166899 -
European Urology Focus Jan 2022Sexual dysfunction is a common side effect of medical therapy for benign prostatic hyperplasia (BPH), whereas prostatic urethral lift (PUL) offers safe and effective...
BACKGROUND
Sexual dysfunction is a common side effect of medical therapy for benign prostatic hyperplasia (BPH), whereas prostatic urethral lift (PUL) offers safe and effective relief of lower urinary tract symptoms while preserving sexual function.
OBJECTIVE
To compare the long-term impact on sexual health of PUL or daily medical therapy of doxazosin or finasteride alone or in combination in BPH patients.
DESIGN, SETTING, AND PARTICIPANTS
This was a comparative analysis of sexual function outcomes from PUL studies (L.I.F.T. [n=107], Crossover [n=42], and MedLift [n=39]) and the Medical Therapy of Prostatic Symptoms (MTOPS) trial. The men included were sexually active with International Prostate Symptom Score ≥13, Qmax ≤12ml/s, and prostate volume 30-80 cm. MTOPS subjects completed the Brief Male Sexual Function Inventory, while PUL subjects completed the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Mean percentage changes from baseline in erectile, ejaculatory, and sexual satisfaction domains were compared at 12, 24, 36, and 48 mo.
RESULTS AND LIMITATIONS
PUL significantly improved erectile function through 24 mo, and ejaculatory function and sexual satisfaction across all time points. Medical therapy did not improve sexual function at any time point. Finasteride significantly decreased erectile function at 48 mo, and combined therapy significantly reduced ejaculatory function at 12 and 24 mo. Comparatively, PUL was superior to finasteride in preserving erectile function at 24 and 48 mo, and superior to doxazosin and combined therapy at 12 mo. PUL outperformed all three medical therapies at all time points in improving ejaculatory function and sexual satisfaction. Limitations include the use of distinct patient-reported questionnaires and narrowed data on comorbidities that influence male sexual function.
CONCLUSIONS
Indirect comparison reveals that PUL is superior to BPH medical therapy in preserving erectile and ejaculatory function and sexual satisfaction.
PATIENT SUMMARY
In our non-head-to-head study, only patients undergoing PUL for an enlarged prostate experienced improvements in sexual health. Conversely, patients on medical therapy experienced worsening of erectile and ejaculatory function.
Topics: Doxazosin; Erectile Dysfunction; Finasteride; Humans; Male; Prostate; Prostatic Hyperplasia
PubMed: 33436276
DOI: 10.1016/j.euf.2020.12.013 -
Iranian Journal of Psychiatry and... Sep 2016Prazosin is significantly effective to reduce sleep disturbance and trauma nightmare in patients with post-traumatic stress disorder (PTSD); however, results of...
BACKGROUND
Prazosin is significantly effective to reduce sleep disturbance and trauma nightmare in patients with post-traumatic stress disorder (PTSD); however, results of different studies were evaluated.
OBJECTIVES
The current randomized clinical trial aimed to assess the effects of prazosin on sleep parameters and nightmares among veterans with chronic PTSD.
MATERIALS AND METHODS
Thirty-two veterans with chronic war-induced PTSD and distressing nightmares were randomized into prazosin and placebo groups for eight weeks. The main symptoms were qualified using the recurrent distressing dreams item of the clinician administered PTSD scale (CAPS) and the daytime symptom severity was measured by PTSD checklist (PCL) and the objective sleep quality assessment by actigraphy.
RESULTS
Compared with placebo, prazosin had no significant effects on reduction of daytime symptoms (P = 0.69) and frequency and intensity of trauma-related nightmares. Also, there were no significant differences between pre- and post-treatment actigraphy measurements (P > 0.05).
CONCLUSIONS
The study findings showed that prazosin had no significant effect on reduction of PTSD symptoms as well as nightmares among veterans with chronic PTSD. Further clinical trials are needed to define the effect of prazosin on sleep physiology and whether such effects regarding the therapeutic response.
PubMed: 27822278
DOI: 10.17795/ijpbs-2603 -
Indian Journal of Pharmacology 2014To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity.
OBJECTIVES
To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity.
MATERIALS AND METHODS
Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed.
RESULTS
Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments.
CONCLUSION
Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection.
Topics: Acetaminophen; Adrenergic Antagonists; Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Carbazoles; Carvedilol; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Glutathione; Liver; Male; Malondialdehyde; Metoprolol; Prazosin; Propanolamines; Protective Agents; Rabbits
PubMed: 25538338
DOI: 10.4103/0253-7613.144937 -
Frontiers in Pharmacology 2015The SLC22A1 influx transporter is expressed on the basolateral membrane of hepatocytes and is involved in the excretion of numerous cations. Inhibition of SLC22A1 by...
The SLC22A1 influx transporter is expressed on the basolateral membrane of hepatocytes and is involved in the excretion of numerous cations. Inhibition of SLC22A1 by several antiretrovirals, such as the protease inhibitor darunavir, has not previously been determined. In order to better understand and predict drug-SLC22A1 interactions, a range of antiretrovirals were screened for SLC22A1-associated inhibition and transport. Stable SLC22A1-expressing KCL22 cells were produced previously by nucleofection. Control KCL22 cells were transfected with the empty vector pcDNA3.1. Accumulation of tetraethylammonium (5.5 μM, 30 min) was determined in SLC22A1-expressing and mock-transfected cells with and without 50 μM of SLC22A1 inhibitor prazosin, or 50 μM of each antiretroviral drug. SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were determined. Cellular accumulation of efavirenz and darunavir was also assessed in SLC22A1-expressing KCL22 cells and reversibility of this accumulation was assessed using prazosin. Tetraethylammonium accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (10.6 ± 0.8 μM vs. 0.3 ± 0.004 μM, p = 0.009) and was significantly reduced in SLC22A1-expressing cells when co-incubated with all antiretrovirals tested except atazanavir, lamivudine, tenofovir, zidovudine, and raltegravir. Particularly noticeable was the predominance of SLC22A1 inhibitors in the protease inhibitor and non-nucleoside reverse transcriptase inhibitor classes. Absolute SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were 21.8, 46.2, and 2.8 μM, respectively. Efavirenz accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (17% higher, p = 0.009) which was reversed using prazosin, whereas no difference was observed for darunavir (p = 0.86). These data inform the mechanistic basis for disposition, drug-drug interactions and pharmacogenetic candidate gene selection for antiretroviral drugs.
PubMed: 25914645
DOI: 10.3389/fphar.2015.00078 -
The Journal of Physiology Apr 2019The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilatation caused by CGRP (and possibly substance P) released from sensory-motor...
KEY POINTS
The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilatation caused by CGRP (and possibly substance P) released from sensory-motor nerves and vasoconstriction caused by noradrenaline, ATP and neuropeptode Y release from sympathetic nerves. Most studies on perivascular nerve-mediated vasodilatation are made in vitro. In the present study, we provide evidence indicating that in vivo electrical perivascular nerve stimulation in rat mesenteric small arteries causes a large β1-adrenoceptor-mediated vasodilatation, which contrasts with a smaller vasodilatation caused by endogenous CGRP that is only visible after inhibition of Y1 NPY receptors.
ABSTRACT
Mesenteric arteries are densely innervated and the nerves are important regulators of vascular tone and hence blood pressure and blood flow. Perivascular sensory-motor nerves have been shown to cause vasodilatation in vitro. However, less is known about their function in vivo. Male Wistar rats (10-12 weeks old; n = 72) were anaesthetized with ketamine (3 mg kg ) and xylazine (0.75 mg kg ) or pentobarbital (60 mg kg ). After a laparotomy, a section of second-order mesenteric artery was visualized in an organ bath after minimal removal of perivascular adipose tissue. The effects of electrical field stimulation (EFS) and drugs on artery diameter and blood flow were recorded with intravital microscopy and laser speckle imaging. EFS caused vasodilatation in arteries constricted with 1 μm U46619 in the presence of 140 μm suramin and 1 μm prazosin. The vasodilatation was inhibited by 1 μm tetrodotoxin and 5 μm guanethidine, although not by the 1 μm of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 μm Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilatation. Atenolol at a concentration 1 μm inhibited the vasodilatation, whereas 0.1 μm of the β -adrenoceptor selective antagonist ICI-118,551 had no effect. Increasing the extracellular [K ] to 20 mm caused vasodilatation but was converted to vasoconstriction in the presence of 1 μm BIBN4096bs, and constriction to 30 mm potassium was potentiated by BIBN4096bs. Atenolol but not BIBN4096bs increased contraction to EFS in the absence of suramin and prazosin. In mesenteric small arteries of anaesthetized rats, EFS failed to stimulate major dilatation via sensory-motor nerves but induced sympathetic β -adrenoceptor-mediated dilatation.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-1 Receptor Antagonists; Animals; Antinematodal Agents; Atenolol; Male; Mesenteric Arteries; Piperazines; Prazosin; Quinazolines; Rats; Rats, Wistar; Receptors, Adrenergic, beta-1; Suramin; Tissue Culture Techniques; Vasoconstriction; Vasodilation
PubMed: 30693527
DOI: 10.1113/JP277368 -
Journal of Clinical Sleep Medicine :... Jan 2015In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS). (Comparative Study)
Comparative Study Meta-Analysis
STUDY OBJECTIVE
In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS).
METHODS
Reference databases were searched for randomized controlled trials using IRT or prazosin for nightmares, sleep disturbance, and/or PTSS. Effect sizes were calculated by subtracting the mean posttest score in the control group from the mean posttest score in the treatment group, and dividing the result by the pooled standard deviation of both groups. Mixed effects models were performed to evaluate effects of treatment characteristics, as well as sample characteristics (veteran vs. civilian) on treatment efficacy.
RESULTS
Four studies used prazosin, 10 used IRT alone or in combination with another psychological treatment, and 1 included a group receiving prazosin and another group receiving IRT. Overall effect sizes of both treatments were of moderate magnitude for nightmare frequency, sleep quality, and PTSS (p < 0.01). Effect size was not significantly different with type of treatment (psychological vs. pharmacological) on nightmare frequency (p = 0.79), sleep quality (p = 0.65), or PTSS, (p = 0.52). IRT combined with CBT for insomnia showed more improvement in sleep quality compared to prazosin (p = 0.03), IRT alone (p = 0.03), or IRT combined with another psychological intervention, (p < 0.01).
CONCLUSION
Although IRT interventions and prazosin yield comparable acute effects for the treatment of nightmares, adding CBT for insomnia to IRT seems to enhance treatment outcomes pertaining to sleep quality and PTSS. More randomized clinical trials with long-term follow-up are warranted.
COMMENTARY
A commentary on this article appears in this issue on page 9.
Topics: Adrenergic alpha-1 Receptor Antagonists; Dreams; Female; Humans; Imagery, Psychotherapy; Male; Prazosin; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Time Factors; Treatment Outcome
PubMed: 25325592
DOI: 10.5664/jcsm.4354 -
Molecular Medicine Reports Feb 2018Ischemic heart disease (including coronary arterial atherosclerosis, or vascular cavity stenosis or occlusion) remains the leading cause of disease‑associated...
Ischemic heart disease (including coronary arterial atherosclerosis, or vascular cavity stenosis or occlusion) remains the leading cause of disease‑associated mortality worldwide. Prazosin, a receptor blocker of postsynaptic adrenaline, is essential in expanding peripheral arteries, which decreases peripheral vascular resistance, and regulates anti‑hypertensive action. However, the mechanisms underlying the effects of prazosin have not been fully elucidated. The aim of the present study was to investigate the protective effects of prazosin on myocardial cells against anoxia‑reoxygenation injury in a mouse model. The regulatory effects of prazosin on blood lipid levels and blood pressure were investigated in experimental mice. Furthermore, inflammation responses and oxidative stress in myocardial cells were analyzed in mice treated with prazosin. Apoptotic myocardial cells were investigated in experimental mice treated with prazosin. In addition, apoptotic gene expression levels were evaluated in myocardial cells. Extracellular signal‑regulated kinase (ERK) expression and phosphorylation was investigated in myocardial cells in mice with anoxia‑reoxygenation injury following prazosin treatment. The activity and expression levels of nuclear factor of activated T cells (NF‑AT), activator protein 1 (AP‑1) and necrosis factor (NF)‑κB were observed in myocardial cells. Furthermore, histological analyses were performed to investigate the benefits of prazosin treatment on anoxia‑reoxygenation injury. The results of the present study identified that prazosin decreased the expression levels of inflammatory factors, interleukin (IL)‑6, tumor necrosis factor (TNF)‑α, IL‑10 and IL‑1 in the serum of mice exhibiting hypoxia/reoxygenation injury. Oxidative stress was observed to be improved and the apoptosis rate was decreased in myocardial cells in anoxia‑reoxygenation injury model mice treated with prazosin. ERK expression and phosphorylation was upregulated, and expression levels of NF‑AT, AP‑1 and NF‑κB were downregulated in the myocardial cells of mice treated with prazosin. Blood lipid levels and blood pressure of the anoxia‑reoxygenation injury model mice were markedly improved following treatment with prazosin. Histological analysis indicated that the area, circumference fragmentation and segmentation of myocardial cells were significantly improved following prazosin treatment. Thus, these results indicate that prazosin treatment decreases inflammation responses, oxidative stress, and apoptosis of myocardial cells via regulation of the ERK signaling pathway. The findings indicate that prazosin may present as a potential therapeutic agent for the treatment of hypoxia/reoxygenation injury.
Topics: Animals; Apoptosis; Biomarkers; Blood Pressure; Cells, Cultured; Cytokines; Disease Models, Animal; Inflammation Mediators; Lipids; MAP Kinase Signaling System; Male; Mice; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidative Stress; Prazosin; Protective Agents
PubMed: 29207167
DOI: 10.3892/mmr.2017.8175