Α1-receptor Blockers Research Articles

Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.

The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α1 receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin. A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values. Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP. Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.

Lifestyle habits to prevent the development of benign prostatic hyperplasia: Analysis of Japanese nationwide datasets.

Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health concern in the aging population. The purpose of this study is to identify modifiable factors, which would prevent or delay BPH development. The association between BPH marker drugs and climate-, socioeconomic-, health condition-, and lifestyle habits-related variables was investigated by analyzing nationwide datasets which were collected in 2018, aggregated by prefecture (administrative unit), and published by Japanese ministries. Uroselective α1 receptor blockers and dutasteride were used as marker drugs referring to BPH prevalence. Correlation analysis, multiple linear regression analysis, and binomial logistic regression analysis were conducted with 47 Japanese prefectures as the unit. The variables which showed |r| > 0.5 by correlation analysis were exercise habits (r=-0.5696), smoking habits (r=0.6116), and daily drinking (r=0.6001) for uroselective α1 receptor blockers, and antihypertensive medication (r=0.5971), smoking habits (r=0.6598), a small amount of drinking (r=-0.5292), and serum alanine aminotransferase (r=0.6814) for dutasteride. Multiple linear regression equations were constructed by including these variables (R 2 =0.5453 for uroselective α1 receptor blockers and R 2 =0.5673 for dutasteride). Binomial logistic regression analysis found a significant association between climate in the resident area and BPH development. This ecological study, analyzing Japanese nationwide datasets, demonstrates that healthy lifestyle habits, especially avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption, are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are suggested as risk factors of BPH development.

A randomized placebo-controlled study: Phellodendron Bawei tablets combined with standard management can improve storage symptoms, sleep quality, and medication compliance in patients with benign prostatic hyperplasia compared to placebo with standard management.

BackgroundBenign prostatic hyperplasia (BPH) is a common micturition disorder in middle-aged and elderly males, and it is one of the most common urology-related diseases worldwide. However, standard therapeutic drugs (α1-receptor blockers + 5α reductase inhibitors) do not provide anti-inflammatory or anti-infective effects. The Phellodendron Bawei tablet is a proprietary Chinese medicine with anti-inflammatory and anti-infective effects. Here, we analyzed whether the combination of standard therapeutic drugs and Phellodendron Bawei tablets has more advantages than placebo with standard management in improving the lower urinary tract symptoms (LUTs), sleep quality, sexual function, and medication compliance in patients with BPH.MethodsThis study was a prospective, double-blind, single-center, 6-month clinical trial in patients with BPH. Male patients, 45–75 years old, a history of moderate-to-severe BPH/LUTs for more than 6 months, moderate-to-severe LUTs [International Prostate Symptom Score (IPSS) ≥8], maximum urine flow rate (Qmax) of <15 mL/s, and prostate volume (PV) of >30 mL. All patients were randomly divided into two cohorts at baseline. The standard management (SM) group was treated with tamsulosin + finasteride + placebo, while the experimental group was treated with tamsulosin + finasteride + Phellodendron Bawei tablets. The clinical indicators were as follows: Age, body mass index (BMI), blood prostate-specific antigen (PSA), PV, Qmax, IPSS; IPSS voiding subscore (IPSS-V), IPSS storage subscore (IPSS-S), and IPSS quality of life (IPSS-QOL)], five-item version of the International Index of Erectile Function (IEFF-5) score, Athens Insomnia Scale (AIS) score, and the Medication Adherence Questionnaire (MAQ). And adverse drug reactions were observed. Student’s t-test was used to analyze results.ResultsWe randomly divided 120 patients into two groups, with 60 patients in each group, and a total of 105 patients completed the study. IPSS-S (P=0.027) and AIS scores (P<0.001) improved more significantly in the Phellodendron Bawei tablets + SM group, and the MAQ score in this group was lower (P=0.003).ConclusionsPhellodendron Bawei tablets combined with α1-receptor blockers and 5α-reductase inhibitors can improve lower urinary tract symptoms associated with urine storage, sleep quality, and medication compliance in patients with benign prostatic hyperplasia compared to placebo with standard management.Trial RegistrationChinese Clinical Trial Registry ChiCTR2100046463.

Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy

AimsSeveral classes of concomitant medications have been shown to affect oncological outcomes in patients with prostate cancer (PCa). We assessed the association between the use of commonly prescribed concomitant medications and biochemical relapse-free survival (bRFS) in patients with localised PCa treated with radiotherapy and androgen deprivation therapy (ADT). Materials and methodsA secondary pooled analysis of two phase III randomised trials was carried out. In the first trial, patients with localised PCa with clinical stage T1b-T3, prostate-specific antigen <30 ng/ml and Gleason score ≤7 were treated with radical radiotherapy and 6 months of ADT starting 4 months before or concomitantly with radiotherapy. In the second trial, patients with high-risk PCa were treated with radical radiotherapy and 36 months of ADT with randomisation to three-dimensional conformal or intensity-modulated radiotherapy. Information on concomitant medications was collected from the medical record. Univariable and multivariable Cox regression was used to identify factors associated with bRFS. ResultsOverall, 486 patients were evaluable. The median follow-up was 125 months; 10-year bRFS was 83.7%. On univariable analysis, receipt of metformin was significantly associated with worse bRFS. Ten-year bRFS was 73% and 85% for patients with and without concomitant metformin (adjusted hazard ratio 2.11, 95% confidence interval 1.03–4.33). Similar evidence of an association was observed with sulfonamide-based α1-receptor blockers (adjusted hazard ratio 2.72, 95% confidence interval 1.31–5.66). However, no such association was seen with receipt of quinazoline-based α1-receptor blockers (adjusted hazard ratio 1.09, 95% confidence interval 0.42–2.82). There was no significant association between bRFS and receipt of all other medication classes considered. ConclusionsIn this population of patients with localised PCa treated with radiotherapy and ADT, receipt of concomitant metformin and sulfonamide-based α1-receptor blockers was associated with inferior biochemical outcome. Randomised trials are required to assess the true effect of these medications on oncological outcomes in localised PCa.

A Soluplus/Poloxamer 407-based self-nanoemulsifying drug delivery system for the weakly basic drug carvedilol to improve its bioavailability

Carvedilol (CAR), a β-adrenoceptor and α1-receptor blocker, has pH-dependent solubility, which greatly limits its oral bioavailability. In this work, a precipitation inhibitor-based self-nanoemulsifying drug delivery system (PI-SNEDDS) was developed by employing Soluplus and Poloxamer 407 to improve drug dissolution and to inhibit drug precipitation in the gastrointestinal tract. In vitro phase distribution and in vivo dissolution studies indicated that PI-SNEDDS significantly increased drug content in the oil phase of the nanoemulsions in the stomach and greatly inhibited the subsequent precipitation of CAR in the intestine compared with the carvedilol self-nanoemulsifying drug delivery system (CAR SNEDDS) and the carvedilol tablets. Moreover, a 1.56-fold increase in the relative bioavailability of CAR was observed for the CAR PI-SNEDDS (397.41%) compared to a CAR SNEDDS (254.09%) with commercial capsules as a reference. Therefore, our developed PI-SNEDDS is a promising vehicle for improving the dissolution and bioavailability of poorly soluble drugs with pH-dependent solubility.

SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (<0.9 nmol/L), plasma metanephrine <0.2 nmol/L (<0.5 nmol/L), 24h urine norepinephrine 987 µg (14 to 80), 24h urine epinephrine 0 (0.5 to 20 µg) and 24h urine dopamine 391 µg (65 to 400). Magnetic resonance imaging (MRI) revealed a 6.5 cm heterogenous and high-vascular mass in right adrenal gland topography. A strong positive uptake was evidenced in the metaiodobenzylguanidine (MIBG) scintigraphy. A selective α1-receptor blocker (prazosin) was started to control blood pressure and adrenergic symptoms. The patient underwent laparoscopic surgery and anatomopathological analysis revealed a 5.5 cm paraganglioma (PASS criteria= 3). The normal right adrenal gland was identified in the histopathology and there was no continuity between normal adrenal gland and neoplasia. After one year of follow-up, the patient is in complete remission. Genetic analysis by Sanger automated sequencing revealed no pathogenic variants in VHL and SDHD genes. We identified a heterozygous germline synonymous variant c.540 G>A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed.

Elucidation of Vasodilation Response and Structure Activity Relationships of N²,N⁴-Disubstituted Quinazoline 2,4-Diamines in a Rat Pulmonary Artery Model.

Pulmonary arterial hypertension (PAH) is a rare and progressive disease arising from various etiologies and pathogenesis. PAH decreases life expectancy due to pulmonary vascular remodeling, elevation of mean pulmonary arterial pressure, and ultimately progresses to heart failure. While clinical treatments are available to reduce the associated symptoms, a complete cure has yet to be found. Phosphodiesterase-5 (PDE-5) inhibition has been identified as a possible intervention point in PAH treatment. The functional vasodilation response to N2,N4-diamino quinazoline analogues with differing PDE-5 inhibitory activities and varying physicochemical properties were assessed in both endothelium-intact and denuded rat pulmonary arteries to gain greater insight into their mode of action. All analogues produced vasorelaxant effects with EC50s ranging from 0.58 ± 0.22 µM to ˃30 µM. It was observed that vasodilation response in intact vessels was highly correlated with that of denuded vessels. The ~10% drop in activity is consistent with a loss of the nitric oxide mediated cyclic guanosine monophosphate (NO/cGMP) pathway in the latter case. A moderate correlation between the vasodilation response and PDE-5 inhibitory activity in the intact vessels was observed. Experimental protocol using the alpha-adrenergic (α1) receptor agonist, phenylephrine (PE), was undertaken to assess whether quinazoline derivatives showed competitive behavior similar to the α1 receptor blocker, prazosin, itself a quinazoline derivative, or to the PDE-5 inhibitor, sildenafil. Competitive experiments with the α1-adrenergic receptor agonist point to quinazoline derivatives under investigation here act via PDE-5 inhibition and not the former. The pre-incubation of pulmonary arterial rings with quinazoline test compounds (10 μM) reduced the contractile response to PE around 40–60%. The most promising compound (9) possessed ~32 folds higher selectivity in terms of vasodilation to its mammalian A549 cell cytotoxicity. This study provides experi0 0mental basis for PDE-5 inhibition as the mode of action for vasodilation by N2,N4-diamino quinazoline analogues along with their safety studies that may be beneficial in the treatment of various cardiovascular pathologies.

The role of sex in intraoperative floppy-iris syndrome

To compare the incidence of intraoperative floppy-iris syndrome (IFIS) between male and female patients undergoing phacoemulsification cataract surgery, evaluate risk factors for its appearance in each sex, and assess any differences in the final visual outcomes. 2nd Department of Ophthalmology, Aristotle University of Thessaloniki, Greece. Comparative retrospective case-control study. Cataract patients with recorded IFIS of any severity occurring over 4years in a tertiary care ophthalmic center during phacoemulsification surgery were identified and enrolled in a multivariate analysis. The study comprised 3811 eyes of 3213 patients. Of the 1678 female patients (1937 eyes) undergoing cataract surgery, IFIS was observed in 25 eyes (1.29%), whereas the incidence of IFIS in male eyes during the same period was statistically significantly higher (97 [5.17%] of 1874 eyes) (P<.0001). No statistically significant difference in age was found between male patients (72.92years±6.5 [SD]) and female patients (72.04±7.1years) (P=.56). An intake of α1-receptor blockers was identified in 70 (72.2%) of 97 male IFIS cases and in none of the 25 female IFIS cases (P<.0001). The posterior capsule rupture rate was significantly higher in 7 (28%) of the 25 female IFIS cases compared with 9 (9.28%) of the 97 male IFIS cases (P=.02). The posterior capsule rupture incidence and final corrected distance visual acuity (with spectacles) were shown to correlate with the IFIS severity grade only in female patients (P<.001 and P=.02, respectively). Although the incidence of IFIS is rarer in female patients, it might significantly affect an increase in the intraoperative events rate and affect the final visual outcome correlating with the severity grade of its appearance. Predisposing risk factors differ between the sexes and surgeons should always be aware of the potentially catastrophic consequences of unforeseen IFIS.

Effect of α-receptor blockers on lower urinary tract symptoms, sexual function and quality of life in young and middle-aged men with benign prostatic hyperplasia.

The purpose of the present study was to compare the effectiveness of two common α1-receptor blockers, alfuzosin and tamsulosin, on lower urinary tract symptoms, sexual function, and quality of life in young and middle-aged people with benign prostatic hyperplasia. We recruited 80 young and middle-aged patients with benign prostatic hyperplasia and divided them into two groups that received either the non-selective α1-receptor blocker alfuzosin or the selective α1A-receptor blocker tamsulosin for 18 consecutive days. After intervention, maximum urinary flow, bladder compliance, maximum detrusor pressure, maximum urethral pressure, 72 h urination frequency and urination frequency at night, average urinary volume, residual urinary volume, urinary symptom distress score were significantly better in the tamsulosin group than in the alfuzosin group. Also, sperm density, sperm motility, sperm activity, and sperm DNA fragmentation index were significantly better in the tamsulosin group compared to the alfuzosin group. Finally, international index of erectile function-5 scores, increased libido and erection, retrograde ejaculation, and the quality of life were significantly better in the tamsulosin group compared to the alfuzosin group. Overall, tamsulosin effectively relieved the lower urinary tract symptoms, improved semen quality, and increased sexual life and quality of life in young and middle-aged patients with benign prostatic hyperplasia.

Effects of Calcineurin Inhibitors on Rat Thoracic and Abdominal Aortae Contractibility and Vasodilatation

Context: Calcineurin inhibitors (CNIs) therapy such as cyclosporine (CsA) and tacrolimus (Tac) are associated with hypertension. Objective: Compare the differential effect of these two agents on thoracic and abdominal aortae. Methods: Thirteen weeks old male Sprague-Dawley rats were treated with CsA (15 mg/kg), Tac (0.15 mg/kg) and vehicle for 15 days. At the end of study, rats were anesthetised, and blood pressure (BP) and heart rate (HR) were measured. Both thoracic (TA) and abdominal (AA) aortae were assessed for the contractibility responses with α1 agonist phenylephrine (PE) against terazosin, a α1 receptor blocker. In addition, vascular relaxation was assessed using endothelium-dependent, Acetylcholine-induced and endothelium-independent sodium nitroprusside-induced pathways in PEconstricted TA and AA. Results: Elevated arterial BP was noted in Tac group, however, HR did not showed any changes in Tac and CsA groups as compared to controls. PEinduced contractibility of TA but not AA was increased significantly and equally by CsA (EC50, 55 ± 7.06 nM) and Tac (EC50, 50 ± 6.6 nM) treatment as compared to control (104 ± 14 nM). ACh-induced endothelium-dependent relaxation was attenuated by both CsA (TA: Imax 66 ± 8.79 %, AA: Imax 74 ± 11.38 %) and Tac (TA: Imax 39 ± 9.55 %, AA: Imax 70 ± 20.06 %), however its intensity was higher in TA by Tac group (controls: 97-98 ± 2.6-2 %). Similarly, SNP-induced endothelium-independent vascular relaxation was also affected by CsA and Tac treatment, TA (IC50 control, 47 ± 11.2 nM, vs. CsA, 214 ± 27.9 nM and Tac, 191 ± 30.8 nM, p< 0.05) and AA (IC50 control, 164 ± 45.1 nM, vs. CsA, 424 ± 53.4 nM and Tac, 520 ± 104.1 nM, p< 0.05). Conclusions: Our functional data confirms that CNIs have differential effects on rat TA and AA via either alternation of vascular relaxations or contractions.

The analysis of transduction mechanisms associated with an acute action of homocysteine on isolated rat femoral artery.

The present study was undertaken in order to examine transduction mechanism involved in the single application of 100 μM homocysteine (Hcy) on isolated rat femoral artery (RFA) rings equilibrated on the basal tone; to establish if a single application of 100 μM Hcy alters contractile effect of phenylephrine (Phe), or oppositely the relaxant effect of acetylcholine (ACh) or bradykinin (BK) after 60-min-long incubation of 100 μM Hcy; and finally to identify morphological changes on the vascular wall after a 24-h-long incubation of 100 μM Hcy. Hcy produced contractile response of intact RFA, which was increased after endothelial denudation, while decreased by urapidil (an α1 receptor blocker), nifedipine (a voltage-gated L-type Ca++ channel blocker) or indomethacin (a cyclooxygenase inhibitor). The initial RFA contraction evoked by Phe was further increased by the single addition of Hcy, which was not the case when ouabain (an inhibitor of Na+/K+-ATPase) was preincubated. After 60-min-long incubation of Hcy relaxant actions of ACh and BK were unaltered, equieffective and equipotent. A 24-h-long incubation of RFA rings with Hcy produced an impairment of vascular endothelium, expressed as a minor or more pronounced interruption of endothelial cells.

Abstract 482: Amyloid-β Peptides Induce a Signal Transduction via Activation of the α1-Adrenoreceptor in Vsmc and Cardiomyocytes

Hypertension is associated with increased risk of Alzheimer disease (AD) that features Amyloid-β peptide (Aβ) deposition in brain (neuritic plaques) and in blood vessels (cerebral amyloid angiopathy). Recently, it was shown by others that Aβ peptides exert a chronotropic effect in neonatal cardiomyocytes, similar to α1-adrenoreceptor autoantibodies (α-AB) as we described earlier. We hypothesized that Aβ peptides elicit a signal transduction pathway in vascular cells, induced by activation of the α1-adrenoreceptor. Aβ peptides (10-35) and (25-35) induced a positive chorontropic effect in the cardiac contraction assay (CCA) after long term activation up to 4 hours (28.84±1.04 bpm and 28.96±1.08 bpm). The effect was attenuated by the α1-receptor blockers urapidil and prazosin (1.72±0.4 bpm and -0.76±1.16 bpm). β1, β2, AT1, or AT2 receptor blockers had no effect on the positive chronotropic effect of Aβ (10-35) and (25-35). Using confocal microscopy and phosphospecific immunoblotting we observed that both peptides induced ERK 1/2 phosphorylation in Chinese hamster ovary (CHO) cells, overexpressing the α1A adrenoreceptor (CHO-α1-AR), but not in wildtype CHO. pERK was also induced in vascular smooth muscle cells (VSMC) and cardiomyocytes. Both Aβ peptides induced an intracellular Ca2+ signal in VSMC. The positive chronotropic response to Aβ (25-35) in the CCA was blocked with a peptide corresponding to the 1st extracellular loop of the α1-AR, the identical epitope to which α1-AB binds. Our data show that Amyloid-β peptides induce a signal transduction cascade via the α1-adrenoreceptor in VSMC and cardiomyocytes. These data might help explain the newly discovered association between hypertension and Alzheimer disease. The role of Aβ peptides in vascular medicine deserves further study.

Progress in inflammatory cardiomyopathy

Viral myocarditis can cause severe myocardial injury and even acute heart failure, then evolve into dilated cardiomyopathy, known as inflammatory cardiomyopathy. Immune reaction plays a key role in the transformation from viral myocarditis into dilated cardiomyopathy, including virus RNA continuous replication,immune-mediated injury, cellular apoptosis, other cellular immune response , myocardial antibodies and other humoral immune response. In the clinical treatment, besides anti-heart failure and cardiac nutrition, the use of ribavirin, α1-receptor blockers, β-receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors and spironolactone should be emphasized. Key words: Inflammatory cardiomyopathy; Immune; Myocarditis

The Efficacy of Prostatic Massage Combined with α1 Receptor Blocker in the Treatment of Type III Prostatitis

Objective To observe the efficacy of prostatic massage combined with α1 receptor blocker in the treatment of type Ⅲ prostatitis. Methods 86 cases were randomly divided into two groups. The treatment group（ n =45 ） were given twice-weekly prostatic massage in combination with α1 receptor blocker（ terazosin 2mg per night） for 6 weeks. Thc control group（n =41 ）were only given terazosin 2mg per night for 6 weeks. AII the patients were asked to complete the National Institutes of Healthe Chronic Prostatitis Symptom Index（NIH-CPSI） before and after the treatment. Results 86 cases were evaluated after the treatment. The NIH-CPSI scores of the two groups decreased from （ 29.5 ± 4.2 ） to （ 9.6 ± 3.8）, from （ 28.9 ± 3.4） to （ 14.6 ± 3.6） respectively, with statistically significant differences from pretreatment（ t = 12.131、6.999, all P 〈 0.05 ）as well as between the combined therapy group and the control group（t = 4.649, P 〈 0.05）. There were no serious side effects during the therapy. Conclusion Prostatic massage combined with α1 receptor blocker can relieve the symptoms in type Ⅲ prostatitis patients and improve their life quality. The combined therapy can produce better efficacy than terazosin used alone. Key words: Prostatitis; Terazosin; Massage

Effectiveness of tamsulosin hydrochloride and its mechanism in improving nocturia associated with lower urinary tract symptoms/benign prostatic hyperplasia

To evaluate the action mechanism of α(1)-receptor blockers in improving nocturia, we have studied effectiveness of tamsulosin hydrochloride (TAM) in the patients with nocturia associated with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). LUTS/BPH patients with nocturia (nocturnal frequency ≥2 times per day) were administered TAM (0.2 mg/day) for 8 weeks. A frequency volume chart (FVC), the International Prostate Symptom Score (I-PSS), quality of life (QOL) index, post-void residual, and uroflowmetry were recorded before and after TAM administration for the patients. The parameters affected by TAM were examined. The FVC and I-PSS of the 160 patients analyzed revealed significant clinical improvements in the nocturnal frequency. On the basis of the FVC, the patients were divided into two groups: the responder group comprising 97 patients with significantly improved nocturnal frequency and the non-responder group comprising 63 patients with less improvement in the nocturnal frequency. Significant differences between groups were observed in the following parameters: the hours of undisturbed sleep (HUS), the interval between the time of sleeping and the first instance of nocturnal voiding, the volume of urine in the first nocturnal voiding episode, nocturnal urine volume, nocturnal polyuria index, daytime urine volume, maximum and average flow rates, and post-void residual. TAM improved the QOL of LUTS/BPH patients by significantly reducing the nocturnal frequency and increasing HUS; moreover, it improved nocturia by decreasing the nocturnal urine volume.

α1-receptor blockers combined with acupuncture treatment efficacy analysis of elderly patients with acute urinary retention

Objective To explore acupuncture and al-receptor blocker treatment efficacy of elderly patients with acute urinary retention. Methods Use of forward-looking monitoring and retrospective survey methodology, Choose January 1,2006 to January 1,2009 of acute urinary retention in 82 cases of elderly inpatients,Chronological order according to treatment group,39 cases were divided into control group,43 cases; Transurethral catheterization in both groups, stay catheter. The control group was treated with α1-receptor blocker hytrin (terazosin) and the application of antibiotics; the treatment group based on the above plus acupuncture therapy. Results The treatment group was 94.87% in the control group response rate was 76.74%, the two groups,P<0.05, the difference was significant. Conclusion al-receptor blockers combined with acupuncture treatment of elderly patients with acute urinary retention al-receptor blocker than simply good effects, synergistic effect, shortening the indwelling catheter time, avoid repeated urinary catheterization and reduce hospital infection, worthy to be popularized. Key words: Acupuncture; al-receptor blocker; Elderly; Acute retention of urine

Blockade of adrenoreceptors inhibits the splenic response to stroke

Recent studies have highlighted the involvement of the peripheral immune system in delayed cellular degeneration after stroke. In the permanent middle cerebral artery occlusion (MCAO) model of stroke, the spleen decreases in size. This reduction occurs through the release of splenic immune cells. Systemic treatment with human umbilical cord blood cells (HUCBC) 24 h post-stroke blocks the reduction in spleen size while significantly reducing infarct volume. Splenectomy 2 weeks prior to MCAO also reduces infarct volume, further demonstrating the detrimental role of this organ in stroke-induced neurodegeneration. Activation of the sympathetic nervous system after MCAO results in elevated catecholamine levels both at the level of the spleen, through direct splenic innervation, and throughout the systemic circulation upon release from the adrenal medulla. These catecholamines bind to splenic α and β adrenoreceptors. This study examines whether catecholamines regulate the splenic response to stroke. Male Sprague–Dawley rats either underwent splenic denervation 2 weeks prior to MCAO or received injections of carvedilol, a pan adrenergic receptor blocker, prazosin, an α1 receptor blocker, or propranolol, a β receptor blocker. Denervation was confirmed by reduced splenic expression of tyrosine hydroxylase. Denervation prior to MCAO did not alter infarct volume or spleen size. Propranolol treatment also had no effects on these outcomes. Treatment with either prazosin or carvedilol prevented the reduction in spleen size, yet only carvedilol significantly reduced infarct volume ( p < 0.05). These results demonstrate that circulating blood borne catecholamines regulate the splenic response to stroke through the activation of both α and β adrenergic receptors.

Perioperative management of late metastasis of pheochromocytoma in clavicle

Perioperative management of late metastasis of pheochromocytoma in clavicle

Effect of Prazosin on the Peripheral Vasculature during Rest Low, Mild, and Heavy Exercise Workloads.

INTRODUCTION: Metabolic inhibition of alpha-1 mediated vasoconstriction in exercising muscles is evident in both animal and human models. A majority of the studies investigating the role of alpha-1 receptors have infused exogenous α1-receptor agonists intra-arterially to activate these receptors. However the role of physiological activation of these receptors in humans is incompletely understood. PURPOSE: To test the hypothesis that as exercise intensity increases physiological activation of α1-receptors has a decreased role in the control of the peripheral vasculature in exercising muscles. METHODS: We compared the vasoconstrictor responses before and after oral ingestion of the α1-receptor blocker Prazosin (1mg/20kg of body weight) in healthy humans (n=5) during rest and dynamic knee-extensor exercise at roughly 40%, 60% and 80% of workloadmax. Neck pressure (NP) stimuli were used to unload carotid baroreceptors thus leading to sympathoexcitation. Ultrasound Doppler provided direct measurements of femoral blood flow (FBF) and intra-arterially measured blood pressures were used to calculate femoral vascular conductance (FVC). RESULTS: Prazosin resulted in significant increases FVC at rest when compared to the control protocol (+68 ± 6%). During exercise the Prazosin mediated increases in FVC decreased with increasing exercise intensities (+68 ± 4%, +39 ±4%, and +23 ± 6% respectively). In both conditions “functional sympatholyis” was occurring because the NP mediated vasoconstriction was attenuated in an exercise intensity dependent manner. During NP the % decreases in FVC were not significantly different between conditions. CONCLUSIONS: These data demonstrate that vasoconstriction elicited by physiological activation of ?1 -receptors with circulating endogenous agonists as a result of intense dynamic exercise is reduced as exercise intensity increases. Additionally there was a reduced response to sympathetically mediated vasoconstriction as a result of functionally unloading the carotid baroreceptors with NP stimuli in both conditions, i.e. functional sympatholysis was present. Furthermore the NP mediated vasoconstriction was attenuated to a similar degree in both conditions. Supported in part by NIH grant # HL-045547

Alfuzosin: an α1-receptor blocker for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia

α1-Receptor blockers have become first-line therapy for the medical management of lower urinary tract symptoms associated with benign prostatic hyperplasia. However, adverse effects such as cardiovascular intolerance can limit their use. This article focuses on alfuzosin, a clinically uroselective, α1-adrenergic antagonist that is available as a novel once-daily formulation that does not require dose titration. Alfuzosin is less vasoactive than other non-subtype selective α1-receptor blockers. In addition to effects on lower urinary tract symptoms, it is also used as an adjunct to urethral catheterisation in patients with acute urinary retention related to benign prostatic hyperplasia, and can improve sexual function and health-related quality of life in benign prostatic hyperplasia sufferers.