Curcumin and α/ß-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB.

Liver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cirrhosis. However, several studies suggest that the toxicity generated by metabolism of these antagonists would hinder its use in cirrhotic patients. In addition, liver fibrosis may be associated with a decrease of the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and the overregulation of the proinflammatory pathway of nuclear factor kappa B (NF-κB). Therefore, in the present work, the capacity of doxazosin (α1 antagonist), carvedilol (nonselective beta-adrenoceptor blocker with alpha 1-blocking properties), and curcumin (antioxidant and anti-inflammatory compound) to reverse liver cirrhosis and studying the possible modulation of Nrf-2 and NF-κB were evaluated. Hamsters received CCl4 for 20 weeks, and then treatments were immediately administered for 4 weeks more. The individual administration of doxazosin or carvedilol showed less ability to reverse cirrhosis in relation to concomitantly curcumin administration. However, the best effect was the combined effect of doxazosin, carvedilol, and curcumin, reversing liver fibrosis and decreasing the amount of collagen I (Sirius red stain) without affecting the morphology of hepatocytes (hematoxylin and eosin stain), showing normal hepatic function (glucose, albumin, AST, ALT, total bilirubin, and total proteins). In addition, carvedilol treatment and the combination of doxazosin with curcumin increased Nrf-2/NF-κB mRNA ratio and its protein expression in the inflammatory cells in the livers, possibly as another mechanism of hepatoprotection. Therefore, these results suggest for the first time that α/ß adrenergic blockers with curcumin completely reverse hepatic damage, possibly as a result of adrenergic antagonism on HSC and conceivably by the increase of Nrf-2/NF-κB mRNA ratio.

Effects of doxazosin mesylate versus nifedipine on blood pressure variability in hypertensive patients: a randomized crossover study (SIMILAR).

OBJECTIVE: Blood pressure variability (BPV) is a powerful predictor of end-organ damage, cardiovascular events and mortality independently of the BP level. Calcium channel blockers may offer an advantage over other first-line antihypertensive drugs by preventing increased BPV. But the effect of alpha-receptor blockers on BPV in hypertensive patients is still unclear. METHODS: In this crossover trial, 36 hypertensive patients were randomly assigned to two groups, receiving doxazosin mesylate gastrointestinal therapeutic system (GITS) (4 mg/day) or nifedipine GITS (30 mg/day) for 12 weeks, followed by a 2-week washout period then a 12-week crossover phase. At baseline and after 12-week treatment, 24-hour ambulatory BP monitoring was performed. BPV was evaluated through standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) of systolic BP (SBP) and diastolic BP (DBP) during daytime, nighttime and over 24 hours. RESULTS: After 12-week treatment, both doxazosin and nifedipine significantly decreased SBP and DBP (P < 0.05), whereas no between-group differences were shown (P>0.05). Systolic BPV (24-hour SD, CV, and ARV; daytime SD; nighttime SD and CV) and diastolic BPV (24-hour SD and ARV) were significantly lowered by nifedipine (P < 0.05); doxazosin resulted in significant reductions of systolic BPV (24-hour SD, CV and ARV; daytime SD; nighttime SD) and diastolic BPV (nighttime SD and CV) (P < 0.05). Doxazosin was revealed to be as effective as nifedipine for reducing BPV (P > 0.05) except for 24-hour SBP ARV. CONCLUSIONS: Doxazosin mesylate GITS had similar therapeutic effects on BP, BP SD, and BP CV lowering as nifedipine GITS in patients with mild-to-moderate essential hypertension.

Is Sexual Function Better Preserved After Water Vapor Thermal Therapy or Medical Therapy for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia?

BACKGROUND: Men often experience deterioration of sexual function after the use of α-blockers and 5-α reductase inhibitors for the treatment of lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia. Thus, an alternative treatment with water vapor thermal therapy (Rezum System, Boston Scientific, Marlborough, MA, USA) which is an efficacious minimally invasive surgical treatment that preserves sexual function was examined. AIM: To compare sexual function over 3 years after continuous daily treatment with pharmaceutical agents in the Medical Therapy of Prostatic Symptoms (MTOPS) study vs a single thermal therapy procedure (Rezum study) in subjects with matched criteria for LUTS severity and prostate size. METHODS: We used sexual function data from sexually active cohorts in the MTOPS study (1,209) randomized to doxazosin, finasteride, combination drugs and placebo, and sexually active men who received thermal therapy (86). MTOPS study participants completed the Brief Male Sexual Function Inventory; men in the Rezum trial completed the International Index of Erectile Function and Male Sexual Health Questionnaire. MAIN OUTCOME MEASURE: Estimated mean changes from baseline for sexual function variables were compared using a linear mixed repeated measures model with fixed effects for treatment and follow-up visits. RESULTS: With continued daily drug use, men experienced significant worsening of sexual desire, erectile and ejaculatory function with finasteride and combination drug therapy, and reduced desire and erectile function with doxazosin. Thermal therapy was not associated with significant negative changes in sexual function throughout 3 years after treatment. CLINICAL IMPLICATIONS: Water vapor thermal therapy can result in greater LUTS improvements than either doxazosin or finasteride alone, whereas combination drug therapy may equal that of this Rezum procedure, but all drug therapies did have a significant negative impact on sexual function in contrast to the preservation of libido, erectile, and ejaculatory function after thermal therapy. STRENGTH & LIMITATIONS: The report includes high-quality data from 2 large randomized controlled trials in subjects with similar baseline inclusion criteria for LUTS severity and prostate size. It is the first longitudinal assessment of sexual function domains restricted to sexually active men treated with drugs or a single minimally invasive surgical treatment with the Rezum procedure. A limitation of the study is the use of 2 different, although validated sexual function inventories (Brief Male Sexual Function Inventory and International Index of Erectile Function). CONCLUSION: A single water vapor thermal therapy procedure for targeted prostate tissue ablation for LUTS/ benign prostatic hyperplasia had no deleterious effect on 4 sexual function domains compared with appreciable worsening of sexual function after long-term single or combination drug use. McVary KT, Rogers T, Mahon J, et al. Is Sexual Function Better Preserved After Water Vapor Thermal Therapy or Medical Therapy for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia? J Sex Med 2018;15:1728-1738.

Three-Year Treatment Outcomes of Water Vapor Thermal Therapy Compared to Doxazosin, Finasteride and Combination Drug Therapy in Men with Benign Prostatic Hyperplasia: Cohort Data from the MTOPS Trial.

PURPOSE: We evaluated the long-term outcomes of treatment of lower urinary tract symptoms due to benign prostatic hyperplasia to compare a 1-time water vapor thermal therapy procedure with daily medical therapy in cohorts from the MTOPS (Medical Therapy of Prostatic Symptoms) study. MATERIALS AND METHODS: Results in the treatment arm of a randomized, controlled trial of thermal therapy using the Rezum® System were compared to MTOPS subjects treated with doxazosin and/or finasteride. Evaluations were restricted to medical therapy subjects, representing 1,140 of the original 3,047 (37.4%), with a prostate volume of 30 to 80 cc and an International Prostate Symptom Score of 13 or greater to include men who met key criteria of the Rezum and MTOPS trials. Outcomes were compared during 3 years for symptom changes and clinical progression rates. RESULTS: Thermal therapy improved symptom scores by approximately 50% throughout 36 months (p <0.0001). Symptom improvement was greater than with either drug alone but similar to that of combination drugs (p ≤0.02 and 0.73, respectively). The peak flow rate improved 4 to 5 ml per second after thermal therapy and doxazosin while thermal therapy was superior to finasteride and combination drugs for 24 and 12 months (p <0.001 and <0.01, respectively). Observed rates of clinical progression during 3 years corroborate these outcomes with approximately 5 times greater progression for any medical therapy vs a single thermal therapy procedure. CONCLUSIONS: A single water vapor thermal therapy procedure provided effective and durable improvements in symptom scores with lower observed clinical progression rates compared to daily long-term use of pharmaceutical agents.

All sorts of tests, only one question: an unexpected cause of hypertension.

A 48-year-old woman presented to the Accident and Emergency department with a 4 month history of headaches, nausea and dizziness. She was found to have severe hypertension and hypokalaemia. Extensive investigations did not find any secondary cause for hypertension. The patient was discharged with oral doxazosin therapy which controlled the blood pressure. Before the follow-up appointment at the hypertension clinic, the patient and her husband identified that her headaches coincided with liquorice tea consumption of up to three cups per day. This information was not obtained in the clinical assessment. The patient is now headache and medication free after cessation of liquorice tea. Liquorice ingestion is often a forgotten reversible cause of hypertension. A good history is key to this diagnosis.

Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary Bladder during Modeled Infravesical Obstruction.

The therapeutic effect of doxazosin (40 µg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P0, markedly increased maximal (premicturitional) pressure Pmax, and increased amplitude of spontaneous oscillations of intravesical pressure ΔPdet in filled bladder. Doxazosin produced no significant effect on Pmax rise during IVO, but prevented elevation of P0 and increment of ΔPdet in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.

[Treatment of Benign Prostatic Hyperplasia by Longbishu Capsule Combined Doxazosin Mesylate Tablet].

Objective To observe the efficacy and safety of Longbishu Capsule (LBS) com- bined Doxazosin Mesylate Tablet (DMT) in treating benign prostatic hyperplasia (BPH). Methods Total- ly 360 BPH with Shen deficiency blood stasis syndrome (SDBSS) were randomly assigned to group A, B, and C, 120 cases in each group. Patients in Group A took LBS placebos combined DMT. Those in Group B took LBS combined DMT. Those in Group C took LBS combined DMT placebos. The dose for LBS was 3 pills each time, 0. 3 g/pill, twice per day. The dose of DMT was 1 tablet each time, 2 mg/tablet, once per day. The therapeutic course for all was 12 months. A total of 113 cases in Group A were recruited in FAS analysis, 115 cases in Group B, and 116 cases in Group C. Main efficacy indicators [International Prostate Symptom Score (IPSS) , maximum urinary flow rate (Qmax) , Quality of Life (QOL) ] , and sec- ondary efficacy indicators [postvoid residual urine volume (PVR) and prostate volume (PV) , symptoms scores of Chinese medicine (CM) I were observed in each group. The efficacy was analyzed in the three groups by taking average age of subjects (66 years) as the hierarchy factor (50 ≤age ≤66 and <66 0. 05). There was no statistical difference in clinical efficacy among post-treatment groups (P >0. 05). The efficacy in subjects more than 66 years old of Group B was superior to that of Group A and C with statistical difference (P <0. 05). Conclusions LBS, DMT, or LBS combined DMT was safe and effective for treating BPH. LBS combined DMT was suit- able for patients complicated with abnormal PVR or aged over 66 years.

[Longbishu Capsule combined with mesylate doxazosin: an efficacious therapy for benign prostatic hyperplasia].

OBJECTIVE: To assess the clinical effect and safety of the Chinese medicine Longbishu Capsule combined with mesylate doxazosin in the treatment of benign prostatic hyperplasia (BPH) of the kidney deficiency and blood stagnation type. METHODS: This was a randomized, double-blind, double-simulation control study. We equally assigned 60 men diagnosed with BPH of the kidney deficiency and blood stagnation type to an experimental and a control group, the former treated with mesylate doxazosin plus Longbishu Capsule and the latter with mesylate doxazosin plus placebo. We compared the International Prostate Symptom Score (IPSS), quality of life (QOL), Chinese symptom score (CSS), maximal urinary flow rate (Qmax), and prostate volume between the two groups of patients before and after 6 months of medication. RESULTS: After treatment, there were 5 cured cases, 13 markedly effective cases, 9 effective cases, 1 ineffective case, and 2 eliminated cases in the experimental group, as compared with 2 cured cases, 8 markedly effective cases, 10 effective cases, 7 ineffective cases, and 3 eliminated cases in the control group. The total effectiveness rate was obviously higher in the former (96.4%) than in the latter (74.1%). IPSS, Qmax, and CSS were improved in both of the groups after medication, even more significantly in the experimental than in the control group (IPSS: 15.22 ± 2.98 vs 18.15 ± 5.88, P <0.05; Qmax: [13.56 ± 2.26] ml/s vs [11.78 ± 2.97] ml/s, P <0.05; CSS: 6.18 ± 2.13 vs 9.52 ± 3.15, P <0.05). Because of the difference in the QOL score between the two groups at the baseline (P = 0.038 <0.05), no more comparison was made in this aspect after treatment. CONCLUSION: The combination of Longbishu Capsule with mesylate doxazosin is safe and effective for the treatment of BPH.

Effect of Longbishu capsule () plus doxazosin on benign prostatic hyperplasia: a randomized controlled trial.

OBJECTIVE: To investigate the effect of Longbishu Capsule (, LBS), doxazosin, and combination therapy on benign prostatic hyperplasia (BPH). METHODS: A randomized, double-blind, multi-center parallel trial was conducted involving 360 patients in hospitals in Beijing (108 cases), Heilongjiang (90 cases), Sichuan (90 cases), Shanghai (72 cases), China. They were randomly assigned with central randomization method to group A (LBS placebo plus doxazosin), group B (LBS plus doxazosin) or group C (LBS plus doxazosin placebo), 120 cases for each group. The international prostate symptom score, maximum urinary flow rate, postvoid residual urine volume and prostate volume were measured for evaluating the efficacy of the three treatments. RESULTS: At baseline, there was no significant difference in the measured variables among the three groups. After 12-month treatment, the three groups showed significant improvements in IPSS and maximum urinary flow rate from baseline (P<0.01). Although postvoid residual urine volume was not significantly different from the baseline in group A (P>0.05), it significantly decreased in group B and C (P<0.05). The incidence of adverse events were similar among the three groups. CONCLUSIONS: The treatment of LBS alone or LBS plus doxazosin was able to significantly improve IPSS in patients with BPH. The treatments may reduce the increase in prostate volume and postvoid residual urine volume as well.

Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration.

A systems pharmacological approach that capitalizes on the characterization of intracellular signaling networks can transform our understanding of human diseases and lead to therapy development. Here, we applied this strategy to identify pharmacological targets for the treatment of Stargardt disease, a severe juvenile form of macular degeneration. Diverse GPCRs have previously been implicated in neuronal cell survival, and crosstalk between GPCR signaling pathways represents an unexplored avenue for pharmacological intervention. We focused on this receptor family for potential therapeutic interventions in macular disease. Complete transcriptomes of mouse and human samples were analyzed to assess the expression of GPCRs in the retina. Focusing on adrenergic (AR) and serotonin (5-HT) receptors, we found that adrenoceptor α 2C (Adra2c) and serotonin receptor 2a (Htr2a) were the most highly expressed. Using a mouse model of Stargardt disease, we found that pharmacological interventions that targeted both GPCR signaling pathways and adenylate cyclases (ACs) improved photoreceptor cell survival, preserved photoreceptor function, and attenuated the accumulation of pathological fluorescent deposits in the retina. These findings demonstrate a strategy for the identification of new drug candidates and FDA-approved drugs for the treatment of monogenic and complex diseases.

Uroterapia en el tratamiento de la incontinencia urinaria / The role of urotherapy in the management of urinary incontinence

El objetivo de este trabajo es presentar nuestros resultados del abordaje de la incontinencia diurna refractaria al tratamiento médico mediante uroterapia. Para ello, se han revisado retrospectivamente las historias de los niños sometidos a este tipo de tratamiento en nuestro centro. Los criterios de inclusión fueron niños con incontinencia diurna refractarios al tratamiento farmacológico, incontinencia de la risa, vejiga hipoactiva y niños en los que se detectó en la cistomanometría una hiperactividad del detrusor y/o incoordinación vesicoesfinteriana. Doce pacientes completaron el seguimiento, con una media de edad de 8,5 años. La indicación más frecuente fue la incontinencia con hiperactividad del detrusor (58,33%). Los resultados fueron satisfactorios en el 83,3% de los casos, con desaparición de los síntomas en 8 pacientes sin tratamiento médico asociado, y 2 más con tratamiento asociado para la eneuresis nocturna. Sólo dos pacientes no presentaron mejoría. La uroterapia es una parte importante del abordaje de la disfunción del tracto urinario inferior en la edad pediátrica. Cabe destacar la importancia de la correcta selección de pacientes y la aplicación adecuada de las diferentes intervenciones, entre las que el biofeedback con imágenes animadas desempeña un papel fundamental(AU)

The aim of this essay is to present our initial results in applying urotherapy to patients with urinary incontinence not responding to pharmacological treatment. We performed ach art review of all the patients treated with urotherapy in our institution. We included all children with incontinence refractory to pharmacological treatment, giggle incontinence, underactive bladder, overactive bladder and dysfunctional voiding. 12 patients completed follow up. Mean age was 8.5 years. The most frequent finding in cystomanometry was detrusor over activity (58.33%). We achieved full response in 83.3% of our patients, 8 of them without any pharmacological treatment, and another 2 with associated administration of desmopressin. Only two patients did not respond to therapy. Urotherapy is an important part of management of lower urinary tract dysfunction in children. Careful selection of the patients and adequate use of every intervention are crucial for its effectiveness(AU)

Papel de los alfa-antagonistas en el síndrome de micción no coordinada en la infancia / Role of alpha antagonists in uncoordinated micturition syndrome in childhood

Introducción. El síndrome de micción no coordinada se caracteriza por un cuadro de disfunción de vaciado vesical debido a la contracción activa del esfínter externo durante el vaciado. Su diagnóstico se basa en los resultados flujoméricos y electromiográficos y el tratamiento está enfocado a mejorar la relajación del esfínter durante la micción, siendo el biofeedback el tratamiento de elección. Dado que aún existen centros sin esta posibilidad, la alternativa son los alfa-bloqueantes, sin mucha literatura al respecto. Objetivo. Determinar la eficacia de los alfa-bloqueantes como tratamiento alternativo al biofeedback en ausencia de este como posibilidad terapéutica. Material y métodos. Presentamos un total de 17 casos de síndrome de Hinman que se encuentran en seguimiento en la consulta de urología pediátrica. Realizamos un estudio retrospectivo. Valoramos la edad y sintomatología al diagnóstico, la presencia de patología urológica asociada, los resultados flujométricos pre y posttratamiento, el tipo (..) (AU)

Introduction. Dysfunctional voiding syndrome in children is characterized by a pattern of dysfunctional bladder emptying due to an active contraction of the external sphincter during micturition. Diagnosis is based on electromyographic and flow metry results. The treatment is focused on relaxing the external sphincter during micturition where biofeedback is the treatment of choice. By the moment there are still centres without this possibility, alpha blockers are an alternative. Objective: To determine the efficacy of alpha blockers as an alternative to biofeedback as a therapeutic possibility. Material and methods: We included a total of 17 children with dysfunctional voiding syndrome and carried out a retrospective study. We registered age, symptoms at diagnosis, presence of associated urologic problems, flow metry results pre and post-treatment, type of treatment used and its effectiveness comparing patients treated with alpha blockers and those who are starting to deal with biofeedback. Results. There were 12 girls and 5 boys. The mean age at diagnosis (..) (AU)

Identification of potential therapeutic targets in hypertension-associated bladder dysfunction.

OBJECTIVE: To investigate differential gene expression profiles in the bladder of spontaneously hypertensive rat (SHR), as the underlying mechanisms involved in hypertension-associated bladder dysfunction remain to be clarified. MATERIALS AND METHODS: SHR and normotensive Wistar-Kyoto (WKY) rats were distributed initially in three groups: group 1 received doxazosin (30 mg/kg/day); group 2 received nifedipine (30 mg/kg/day); and group 3 received the vehicle orally for 4 weeks. The alterations in gene expression levels of candidate genes identified by microarray analysis with potential biological relevance were verified by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Voiding frequency was significantly higher, and mean voided volume was significantly lower in untreated SHRs than untreated WKY rats. Microarray analysis revealed that 25 of the differentially expressed genes in untreated SHRs compared to untreated WKY rats were related to G(s), G(i), G(q) and G(12/13) signalling, calcium handling, ion transport and smooth muscle-related genes. Furthermore, RT-PCR data, in accord with the microarray analysis, indicated that untreated SHRs had lower mRNA expression levels of Adcy2, Adcy3, Rgs2, Rgs3, Rgs4 and Arhgdia, and higher mRNA expression levels of Arhgef1, Arhgef11, Arhgef12, Geft, Rock1 and Rock2 than untreated WKY rats. The differential alterations in the micturition patterns and in the expression of several genes related to G-protein signalling pathway observed in SHRs were attenuated by treatment with doxazosin, but not nifedipine. CONCLUSION: Our data suggest that differential alterations in the expression of several genes related to G(s), G(q) and G(12/13) signalling pathways in the SHR bladder might be important in hypertension-associated bladder dysfunction.

[Kidney-tonifying and dampness-expelling Chinese herbal medicine combined with doxazosin for the treatment of chronic epididymitis].

OBJECTIVE: To study the clinical effects of kidney-tonifying and dampness-expelling Chinese herbal medicine combined with doxazosin in the treatment of chronic epididymitis. METHODS: A total of 64 patients with chronic epididymitis were equally randomized into a treatment and a control group, the former treated with kidney-tonifying and dampness-expelling Chinese herbal decoction combined with doxazosin, and the latter given doxazosin only, both for 4 weeks. The clinical symptoms were measured by Chronic Epididymitis Symptom Index (CESI), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) before and after the treatment, and the therapeutic effects were evaluated. RESULTS: After 4 weeks of medication, the total mean scores on CESI, pain, and quality of life (QOL) were significantly decreased in both the treatment and the control groups (P < 0.05), even more significantly in the former than in the latter (P < 0.05), and so were the scores on SAS and SDS (P < 0.05), but with no significant differences between the two groups (P > 0.05). CONCLUSION: Either doxazosin alone or kidney-tonifying and dampness-expelling Chinese herbal decoction combined with doxazosin is obviously effective on chronic epididymitis, but the combined medication produces an even better efficacy.

Assessment of therapeutic drug efficiency.

The efficiency of drug therapy should be evaluated by not only its directed action on specific organ or target parameter, but also its effects on general regulatory and adaptive status.

[Medication combined with local hyperthermia: a desirable therapy for chronic prostatitis pain symptoms].

OBJECTIVE: To compare the effect of the combined therapy of medication with local hyperthermia with that of the simple local hyperthermia therapy in the treatment of pain symptoms of chronic prostatitis (CP). METHODS: Seventy-six CP patients aged 18-48 (mean 29.2 +/- 3.8) years, with the disease course of 3.5-180 (mean 8.0 +/- 1.2) months and NIH-CPSI pain score > or = 14, were equally randomized into a treatment group and a control. The former was treated by applying the CRS-2280E extraorgan short-wave capacitance field hyperthermia system to the prostate once an hour every other day for 7 times, combined with anal administration of 1 Qianliean suppository and oral doxazosin 4 mg before bedtime every night for 2 weeks, while the latter underwent simple local hyperthermia. All the patients were scored on NIH-CPSI and the therapeutic results were compared between the two groups. RESULTS: The pre- and post-treatment NIH-CPSI scores were (23.9 +/- 3.8) and (5.2 +/- 3.1) (P < 0.01) in the treatment goup and (24.5 +/- 4.3) and (11.6 +/- 3.4) (P < 0.01) in the control; the pre- and post-treatment scores on NIH-CPSI pain symptoms were (16.5 +/- 1.9) and (3.1 +/- 2.2) (P < 0.01) in the former and (15.9 +/- 1.7) and (8.2 +/- 2.0) (P < 0.01) in the latter. The total score on NIH-CPSI and that on NIH-CPSI pain symptoms were both significantly higher in the treatment group than in the control (P < 0.01). Within the treatment group, the score on NIH-CPSI pain symptoms was even more significantly improved in patients with the first attacks than in those already treated by other means (P < 0.01). No adverse effects were observed in either of the groups. CONCLUSION: Both the combined therapy of medication with local hyperthermia and simple local hyperthermia are effective, safe and tolerable in the treatment of CP pain symptoms, and the former is even more desirable, particularly for those with the first attacks of the symptoms.

[Comparison of different drugs on the treatment of benign prostate hyperplasia].

OBJECTIVE: To compare the differences of the efficacy and different therapeutic drugs on the treatment of benign prostatic hyperplasia (BPH) in order to ensure the optimal indication for different BPH patients. METHODS: A randomized, parallel-controlled, multicenter clinical trial was conducted. From September 2002 to December 2003 906 BPH patients were enrolled into 7 therapeutic groups, including selective-adrenoceptor antagonist (terazosin, doxazosin tamsulosin and naftopidil), 5 alpha-reductase inhibitor (finasteride and epristeride) and natural product (cernilton). International Prostate Symptom Score (IPSS) and Quality of Life (QOL), uroflowmetry, total prostatic volume (TPV) and transitional zone volume and residual urine were used as efficacy criteria. RESULTS: According to the baseline, the IPSS and Qmax were significantly correlated to the prostatic volume and transitional zone volume (P < 0.01). At average follow-up of 6 months, significant improvements in IPSS, QOL, Qmax and residual urine volume were observed in each therapeutic group, and no difference in IPSS improvement was found among the groups. Prostatic volume and transitional zone volume were significant decreased in 5alpha-reductase inhibitor groups (P < 0.05). In patients with baseline TPV greater than 35.5 cm3, the improvement of Qmax was more significant than that in patients with TPV less than 35.5 cm3 in finasteride group (P < 0.01) (5.7 ml/s and 2.2 ml/s respectively), and more significant symptomatic improvements were also found in cernilton, doxazosin and naftopidil group. In each group, the improvement of symptom were more significant in patients with IPSS higher than 20 points (P < 0.01). CONCLUSIONS: Each drug observed in this study can improve the subjective and objective symptoms significantly for BPH patients, especially for patients with higher IPSS baseline. When using 5alpha-reductase inhibitor, prostatic volume can be decreased significantly and more obviously subjective and objective improvement can be found in the patients with TPV greater than 35.5 cm3.

[Benign prostatic hyperplasia: medical therapy]. / Prostatagrösse, PSA-Wert, Leidensdruck. Die Wegweiser für die medikamentöse Therapie.

Primary aims of the medical therapy for BPH are improvement of subjective symptoms and quality of life as well as the prevention of long-term complications such as acute urinary retention and renal failure. Secondary goal is inhibition of disease progression. The medical therapy should be tailored to each patient according to the individual complaints and risk of progression. Plant extracts, alpha-blockers and 5-alpha reductase inhibitors represent the most common prescribed substances. Recent data suggest beneficial effects for the use of antimuscarinic agents and phosphodiesterase type 5 inhibitors.

Pharmacologic expulsive treatment of ureteral calculi.

OBJECTIVE: To evaluate the role of nifedipine and the alpha(1)-adrenoreceptor antagonists tamsulosin, terazosin, and doxazosin in the expulsive treatment of ureteral calculi. DATA SOURCES: Literature was searched via MEDLINE (1966-February 2006) with subsequent bibliographic review. MeSH headings included ureteral calculi, nifedipine, doxazosin, and adrenergic alpha-antagonists. Key terms were ureteral calculi, nifedipine, tamsulosin, terazosin, and doxazosin. STUDY SELECTION AND DATA EXTRACTION: Trials evaluating nifedipine, tamsulosin, terazosin, and doxazosin for expulsion of ureteral stones were reviewed. All were published in English-language, peer-reviewed journals. DATA SYNTHESIS: Several trials have evaluated the effects of nifedipine and tamsulosin on ureteral stone passage rates and mean time to stone passage in stones no larger than 15 mm. In 28 day trials, the rates of ureteral stone passage were 35-70% in the control groups compared with 77.1-80% in patients treated with nifedipine and 79.3-100% in patients treated with tamsulosin. Average number of days to stone passage in the control groups was 4.6-20, and the time to stone passage was only 5-9.3 days in patients receiving nifedipine and 2.7-7.9 days in those receiving tamsulosin. The stone passage rates and time to stone passage appeared to be similar in one trial that compared tamsulosin with terazosin and doxazosin. Limited data suggest that these agents may have a role as adjuncts to shock wave lithotripsy. Adverse drug reactions were uncommon. CONCLUSIONS: Nifedipine, tamsulosin, terazosin, and doxazosin are safe and effective options in enhancing ureteral stone expulsion in selected patients with uncomplicated presentations.

Treatment and pharmacologic management of BPH in the context of common comorbidities.

Benign prostatic hyperplasia (BPH) is extremely common in the aging man and may cause significant lower urinary tract symptoms (LUTS) necessitating treatment. Drug treatment is the mainstay of treatment for symptomatic BPH and is directed at relaxing prostatic smooth muscle, reducing prostate volume, or a combination of these effects. The most commonly used drugs for this indication are alpha1-adrenergic receptor antagonists, which relax prostatic smooth muscle, and 5-alpha-reductase inhibitors, which reduce prostatic androgen levels and consequently prostate size. Invasive interventions include the gold standard, transurethral resection of the prostate (TURP), and several minimally invasive surgical options. Although effective in alleviating symptoms, TURP carries a higher risk of morbidity and complications, including sexual side effects (mainly ejaculatory dysfunction), than medical therapy or minimally invasive techniques. Treatment for BPH, whether medical or surgical, must take patients' comorbid conditions into consideration so that LUTS may be effectively relieved, with the smallest risk of exacerbating any concomitant conditions.