Use, Misuse and Abuse of Testosterone and Other Androgens.

INTRODUCTION: For several decades, testosterone and its synthetic derivatives have been used for anabolic and androgenic purposes. Initially restricted to professional bodybuilders, these substances gradually became more popular with recreational weightlifters. Considering its increasing prevalence, the consumption of anabolic androgenic steroids (AAS) has become a matter of great concern. Although most side effects are mild and reversible, some of them can cause permanent damage or can be potentially life threatening. OBJECTIVES: To review and summarize medical literature regarding misuse and abuse of testosterone and other androgens, in order to provide evidence-based information on the main topics related to this subject, such as how to identify and how to deal with these patients, and to elucidate the multiple possible adverse effects secondary to this practice. METHODS: Key studies were retrieved from PubMed (1989-2021) with reference searches from relevant articles. Search terms included "hypogonadism", "anabolic androgenic steroids", "androgens", "misuse AND testosterone", "abuse AND testosterone", and "side effects AND testosterone". RESULTS: There is a significant lack of information in the peer-reviewed literature describing demographic data, implications for different organ systems and the management of current or former AAS users; however, androgen abuse has been already linked to a wide variety of cardiovascular diseases, metabolic, endocrine, neurological, psychiatric and liver disorders. Despite all this, most physicians still feel uncomfortable and hesitate to discuss the issue with patients. CONCLUSIONS: The chronic use of high doses of AAS is associated with adverse effects in several organ systems; however, there are still many gaps in our knowledge about the long-term consequences of this practice and how to deal with these patients. Healthcare professionals have a crucial role in combating this public health problem, recognizing and preventing the spread of androgen abuse.

Use, Misuse and Abuse of Testosterone and Other Androgens.

INTRODUCTION: For several decades, testosterone and its synthetic derivatives have been used for anabolic and androgenic purposes. Initially restricted to professional bodybuilders, these substances gradually became more popular with recreational weightlifters. Considering its increasing prevalence, the consumption of anabolic androgenic steroids (AAS) has become a matter of great concern. Although most side effects are mild and reversible, some of them can cause permanent damage or can be potentially life threatening. OBJECTIVES: To review and summarize medical literature regarding misuse and abuse of testosterone and other androgens, in order to provide evidence-based information on the main topics related to this subject, such as how to identify and how to deal with these patients, and to elucidate the multiple possible adverse effects secondary to this practice. METHODS: Key studies were retrieved from PubMed (1989-2021) with reference searches from relevant articles. Search terms included "hypogonadism", "anabolic androgenic steroids", "androgens", "misuse AND testosterone", "abuse AND testosterone", and "side effects AND testosterone". RESULTS: There is a significant lack of information in the peer-reviewed literature describing demographic data, implications for different organ systems and the management of current or former AAS users; however, androgen abuse has been already linked to a wide variety of cardiovascular diseases, metabolic, endocrine, neurological, psychiatric and liver disorders. Despite all this, most physicians still feel uncomfortable and hesitate to discuss the issue with patients. CONCLUSIONS: The chronic use of high doses of AAS is associated with adverse effects in several organ systems; however, there are still many gaps in our knowledge about the long-term consequences of this practice and how to deal with these patients. Healthcare professionals have a crucial role in combating this public health problem, recognizing and preventing the spread of androgen abuse. Linhares BL, Miranda EP, Cintra AR, et al. Use, Misuse and Abuse of Testosterone and Other Androgens. Sex Med Rev 2022;10:583-595.

Effect of co-administration of two different phosphodiesterase inhibitors and a ß3-adrenoceptor agonist in an experimental model of detrusor overactivity.

The purpose of this study was to evaluate in vitro the effect of the combination of BRL 37344 (ß3-adrenoceptor agonist) with tadalafil (phosphodiesterase type 5 inhibitor) or rolipram (phosphodiesterase type 4 inhibitor) in an experimental model of detrusor overactivity. The experiments were carried out in two phases using bladder strips of mice. In the first phase, on the top of 40 mM potassium-induced contraction, strips isolated from control mice were exposed to increasing concentrations of each study drug. In another series of experiments, prior to contraction, strips were incubated with either tadalafil or rolipram, followed by the addition of increasing concentrations of BRL 37344. In the second phase, the same protocols were performed with animals previously treated with L-NAME for 30 days. Chronic L-NAME administration leads to detrusor overactivity due to nitric oxide synthase inhibition. In phase one, preincubation with tadalafil enhanced relaxation response to BRL 37344 at two concentrations. Pretreatment with rolipram had no effect on BRL 37344-induced relaxation. In L-NAME-treated mice, rolipram induced more relaxation than the other drugs, enhancing relaxation response to BRL 37344 at almost all concentrations, but no synergistic effect with tadalafil was observed. The relaxant effect of BRL 37344 was enhanced by rolipram but not by tadalafil, suggesting that PDE4 inhibition, especially when associated with ß3-adrenoceptor stimulation, could represent a potential treatment for overactive bladder.

Impact of testicular sperm extraction and testicular sperm aspiration on gonadal function in an experimental rat model

ABSTRACT Purpose To assess the impact of sperm retrieval on the gonadal function of rats with impaired spermatogenesis by comparing testicular sperm extraction (TESE) to aspiration (TESA). The efficacy of these procedures to sperm obtainment was also compared. Materials and Methods A pilot study showed impaired spermatogenesis, but normal testosterone (T) production after a bilateral orchidopexy applied to 26 rats, which were randomly assigned into four groups: TESE (n=7), TESA (n=7), SHAM (n=6) and Control (n=6). The T levels were measured through comparative analysis after the orchidopexy. Results There was no statistical difference in the animal's baseline T levels after orchidopexy in comparison to the controls: the TESE and TESA groups, 6.66±4.67ng/mL; the SHAM group (orchidopexy only), 4.99±1.96ng/mL; and the Control, 4.75±1.45ng/mL, p=0.27. Accordingly, no difference was found in the postoperative T levels: TESE, 5.35±4.65ng/mL; TESA, 3.96±0.80ng/mL; SHAM, 3.70±1.27ng/mL; p=0.4. The number of sperm cells found through TESE (41.0±7.0) was significantly larger than that found through TESA (21.3±8.1, p=0.001). Moreover, higher tissue weight was found through TESE (0.09±0.02g versus 0.04±0.04g, p=0.04). Conclusions The testicular sperm capture performed in rats through extraction or aspiration, after orchidopexy, did not significantly decrease the T levels. The amount of sperm found through testicular sperm extraction was higher than that through testicular sperm aspiration.

Impact of testicular sperm extraction and testicular sperm aspiration on gonadal function in an experimental rat model.

PURPOSE: To assess the impact of sperm retrieval on the gonadal function of rats with impaired spermatogenesis by comparing testicular sperm extraction (TESE) to aspiration (TESA). The efficacy of these procedures to sperm obtainment was also compared. MATERIALS AND METHODS: A pilot study showed impaired spermatogenesis, but normal testosterone (T) production after a bilateral orchidopexy applied to 26 rats, which were randomly assigned into four groups: TESE (n=7), TESA (n=7), SHAM (n=6) and Control (n=6). The T levels were measured through comparative analysis after the orchidopexy. RESULTS: There was no statistical difference in the animal's baseline T levels after orchidopexy in comparison to the controls: the TESE and TESA groups, 6.66±4.67ng/mL; the SHAM group (orchidopexy only), 4.99±1.96ng/mL; and the Control, 4.75±1.45ng/ mL, p=0.27. Accordingly, no difference was found in the postoperative T levels: TESE, 5.35±4.65ng/mL; TESA, 3.96±0.80ng/mL; SHAM, 3.70±1.27ng/mL; p=0.4. The number of sperm cells found through TESE (41.0±7.0) was significantly larger than that found through TESA (21.3±8.1, p=0.001). Moreover, higher tissue weight was found through TESE (0.09±0.02g versus 0.04±0.04g, p=0.04). CONCLUSIONS: The testicular sperm capture performed in rats through extraction or aspiration, after orchidopexy, did not significantly decrease the T levels. The amount of sperm found through testicular sperm extraction was higher than that through testicular sperm aspiration.

Overactive bladder - 18 years - Part I.

Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals - including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years.

Overactive bladder - 18 years - Part II.

Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics - pillars of the overactive bladder pharmacotherapy - started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning - as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder - 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

Overactive bladder - 18 years - Part II

ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

Overactive bladder - 18 years - Part I

ABSTRACT Abstract: Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals – including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years.

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency.

PURPOSE: The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. MATERIALS AND METHODS: Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. RESULTS: The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. CONCLUSION: In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles. .

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide.

PURPOSE: Recently, the effect of phosphodiesterase inhibitors (PDE5i) in the lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia have been studied thoroughly. However, it remains unclear how the PDE5i improve LUTS. Therefore, the aim of the present study was to evaluate the potential of acute administration of the PDE5i sildenafil to improve detrusor overactivity (DO) induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), an nitric oxide sinthase (NOS) inhibitor, in rats. MATERIALS AND METHODS: Twenty-seven MALE adult Wistar Rats were divided into the following groups: (1) control, (2) L-NAME, (3) sildenafil alone, and (4) L-NAME + sildenafil. The NOS blocker L-NAME (20 mg/rat/day) was given in the drinking water. Sildenafil (100 µg/kg) was administrated intravenously (i.v.) acutely, diluted in cremophor, propylene glycol and water. All animals underwent to anesthetized cystometograms. RESULTS: The chronic and systemic administration of L-NAME markedly increased the number of non voiding contractions (2.62 (± 0.89)), and frequency of micturition (1.97 (± 0.78)), as well increased volume threshold (2.83 mL (± 1.64)) compared with control group, the number of non voiding contractions (1.17 (± 0.75)), frequency of micturition (1.08 (± 0.65)) and volume threshold (1.16 mL (± 0.38)), p < 0.001, p = 0.01, and p = 0.04, respectively. Sildenafil infusion decreased the number of micturition cycles significantly from the baseline to end point (-0.93 (± 0.34)) in nitric oxide (NO) deficient animals compared with sildenafil infusion alone (control) in animals with normal NO level (0.13 (± 0.25)), p = 0.03. CONCLUSION: Systemic reduction of nitric oxide causes detrusor overactivity and acute infusion of sildenafil reduces the number of micturition cycles in chronic NO-deficient rats.

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

Purpose Recently, the effect of phosphodiesterase inhibitors (PDE5i) in the lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia have been studied thoroughly. However, it remains unclear how the PDE5i improve LUTS. Therefore, the aim of the present study was to evaluate the potential of acute administration of the PDE5i sildenafil to improve detrusor overactivity (DO) induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), an nitric oxide sinthase (NOS) inhibitor, in rats. Materials and Methods Twenty-seven MALE adult Wistar Rats were divided into the following groups: (1) control, (2) L-NAME, (3) sildenafil alone, and (4) L-NAME + sildenafil. The NOS blocker L-NAME (20 mg/rat/day) was given in the drinking water. Sildenafil (100µg/kg) was administrated intravenously (i.v.) acutely, diluted in cremophor, propylene glycol and water. All animals underwent to anesthetized cystometograms. Results The chronic and systemic administration of L-NAME markedly increased the number of non voiding contractions (2.62 (± 0.89)), and frequency of micturition (1.97 (± 0.78)), as well increased volume threshold (2.83 mL (± 1.64)) compared with control group, the number of non voiding contractions (1.17 (± 0.75)), frequency of micturition (1.08 (± 0.65)) and volume threshold (1.16 mL (± 0.38)), p < 0.001, p = 0.01, and p = 0.04, respectively. Sildenafil infusion decreased the number of micturition cycles significantly from the baseline to end point (-0.93 (± 0.34)) in nitric oxide (NO) deficient animals compared with sildenafil infusion alone (control) in animals with normal NO level (0.13 (± 0.25)), p = 0.03. Conclusion Systemic reduction of nitric oxide causes detrusor overactivity and acute infusion of sildenafil reduces the number of micturition cycles in chronic NO-deficient rats. .

Urodynamic effects of the combination of tamsulosin and daily tadalafil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, placebo-controlled clinical trial.

OBJECTIVES: To evaluate the effect of association of tamsulosin/tadalafil taken daily compared with tamsulosin/placebo in the lower urinary tract with urodynamic study (UDS). METHODS: All patients underwent baseline UDS before randomization to tamsulosin 0.4 mg/tadalafil 5 mg (Group 1; n = 20) or tamsulosin 0.4 mg/placebo (Group 2; n = 20) once daily for 30 days. End-of-study UDS were performed on completion of the treatment period. The primary end point was to demonstrate changes in urodynamic variables in the voiding phase, detrusor pressure at maximum flow (PdetQmax), and maximum flow rate (Qmax), from baseline to week four. RESULTS: The primary outcome measure of this clinical trial, PdetQmax, showed a significant reduction in tamsulosin/tadalafil group (13 ± 17.0) compared to tamsulosin/placebo (-1.2 ± 14.35) group (P = 0.03). Qmax increased in both groups, tamsulosin/tadalafil (1.0 ± 2.4) and tamsulosin/placebo (1.4 ± 2.4), but the difference was not significant between treatment groups (P = 0.65). Total IPSS, storage, and voiding sub-score improved significantly in tamsulosin/tadalafil compared with tamsulosin/placebo group. CONCLUSIONS: The association of tamsulosin/tadalafil reduces detrusor pressure at maximum flow without changing the maximum flow rate during micturition and significantly improves lower urinary tract symptoms compared with the isolated use of tamsulosin.

Retrograde autologous priming in cardiopulmonary bypass in adult patients: effects on blood transfusion and hemodilution / Perfusato autólogo retrógrado no circuito de circulação extracorpórea em pacientes adultos: efeitos sobre a hemodiluição e transfusão de sangue

INTRODUCTION: Retrograde autologous priming (RAP) is a cardiopulmonary bypass (CPB) method, at low cost. Previous studies have shown that this method reduces hemodilution and blood transfusions needs through increased intra-operative hematocrit. OBJECTIVE: To evaluate RAP method, in relation to standard CPB (crystalloid priming), in adult patients. METHODS: Sixty-two patients were randomly allocated to two groups: 1) Group RAP (n = 27) of patients operated using the RAP and; 2) Control group of patients operated using CPB standard crystalloid method (n = 35). The RAP was performed by draining crystalloid prime from the arterial and venous lines, before CPB, into a collect recycling bag. The main parameters analyzed were: 1) CPB hemodynamic data; 2) Hematocrit and hemoglobin values; 3) The need for blood transfusions. RESULTS: It was observed statistically significant fewer transfusions during surgery and reduced CPB hemodilution using RAP. The CPB hemodynamic values were similar, observing a tendency to use lower CPB flows in the RAP group patients. CONCLUSION: This investigation was designed to be a small-scale pilot study to evaluate the effects of RAP, which were demonstrated concerning the CPB hemodilution and blood transfusions.

INTRODUÇÃO: Perfusato autólogo retrógrado (PAR) é uma técnica de circulação extracorpórea (CEC) com baixos custos. Estudos anteriores demonstraram que esta técnica reduz a hemodiluição e a necessidade de transfusões de sangue por meio do aumento do hematócrito intraoperatório. OBJETIVO: Avaliar técnica de PAR em relação à CEC técnica padrão (perfusato cristaloide) em pacientes adultos. MÉTODOS: Sessenta e dois pacientes foram aleatoriamente alocados em dois grupos: 1) Grupo PAR (n = 27), constituído por pacientes operados utilizando a técnica de PAR e; 2) Grupo Controle, constituído por pacientes operados utilizando técnica padrão de CEC com cristaloides (n = 35). A PAR foi realizada drenando-se o perfusato cristaloide das linhas arterial e venosa, antes da CEC, para uma bolsa coletora de recirculação. Os principais parâmetros analisados foram: 1) parâmetros hemodinâmicos da CEC; 2) valores de hematócrito e hemoglobina; e; 3) necessidade de transfusões de sangue. RESULTADOS: Observaram-se diferenças estatisticamente significativas de transfusão no intraoperatório e diminuição da hemodiluição em CEC utilizando PAR. Os valores hemodinâmicos durante a CEC foram semelhantes, observando-se tendência de utilização de fluxos menores na CEC dos pacientes do grupo PAR. CONCLUSÃO: O presente estudo foi projetado em pequena escala para avaliar os efeitos do PAR, o que foi demonstrado em relação aos já conhecidos efeitos na diminuição da hemodiluição em CEC e transfusão sanguínea, porém não mostrou vantagens hemodinâmicas em relação à técnica padrão com perfusato cristaloide.

Long-term administration of BAY 41-2272 prevents bladder dysfunction in nitric oxide-deficient rats.

AIMS: Chronic blockade of nitric oxide (NO) synthesis leads to detrusor smooth muscle overactivity. This study aimed to evaluate the protective effects of BAY 41-2272, a soluble guanlylate cyclase activator, on changes in cystometric parameters in NO-deficient rats. METHODS: Rats were divided into the following groups: (a) control, (b) DMSO, (c) N(ω)-nitro-L-arginine methyl ester hydrochrolide (L-NAME), (d) BAY 41-2272 alone, and (e) L-NAME + BAY 41-2272. The NO synthase blocker L-NAME (20 mg/rat/day) was giving in the drinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage). RESULTS: Chronic L-NAME treatment markedly increased the mean arterial blood pressure (MABP), and co-treatment with BAY 41-2272 nearly reversed L-NAME-induced rise on MABP. Non-void contractions were significantly increased in L-NAME group (0.90 ± 0.1 number/min) compared with either DMSO or control group (0.49 ± 0.1 number/min), which were prevented by co-treatment with BAY 41-2271 (0.56 ± 025 number/min; P < 0.05). The threshold pressure and peak pressure increased by 70% and 44% after chronic L-NAME treatment, while co-treatment with BAY 41-2272 largely attenuated both of these effects (27% and 22% increase, respectively). The frequency of micturition cycles decreased by about of 50% in L-NAME-treated rats compared with control animals, and co-treatment with BAY 41-2272 normalized this parameter. CONCLUSIONS: Our data show that long-term oral administration of BAY 41-2272 counteracts the bladder dysfunction seen in NO-deficient rats, indicating that restoration of the NO-cGMP pathway by this compound may be of beneficial value to treat bladder symptoms.

Retrograde autologous priming in cardiopulmonary bypass in adult patients: effects on blood transfusion and hemodilution.

INTRODUCTION: Retrograde autologous priming (RAP) is a cardiopulmonary bypass (CPB) method, at low cost. Previous studies have shown that this method reduces hemodilution and blood transfusions needs through increased intra-operative hematocrit. OBJECTIVE: To evaluate RAP method, in relation to standard CPB (crystalloid priming), in adult patients. METHODS: Sixty-two patients were randomly allocated to two groups: 1) Group RAP (n = 27) of patients operated using the RAP and; 2) Control group of patients operated using CPB standard crystalloid method (n = 35). The RAP was performed by draining crystalloid prime from the arterial and venous lines, before CPB, into a collect recycling bag. The main parameters analyzed were: 1) CPB hemodynamic data; 2) Hematocrit and hemoglobin values; 3) The need for blood transfusions. RESULTS: It was observed statistically significant fewer transfusions during surgery and reduced CPB hemodilution using RAP. The CPB hemodynamic values were similar, observing a tendency to use lower CPB flows in the RAP group patients. CONCLUSION: This investigation was designed to be a small-scale pilot study to evaluate the effects of RAP, which were demonstrated concerning the CPB hemodilution and blood transfusions.

Administração de BAY 41-2272 previne disfunção vesical em ratos deficientes de oxido nítrico / Administration of BAY 41-2272 prevents bladder dysfunction in nitric-oxide deficient rats

Objective: to evaluate the protective effects of BAY 41-2272, a soluble guanylate cyclase activator, on changes in cystometric parameters in rats deficient in nitric oxide (NO). Methods: Rats were divided into the following groups: (a) control; (b) DMSO; (c) L-NAME; (d) BAY 41-2272 alone; (e) L-NAME + BAY 41-2272. The NO synthase blocker L-NAME (20 mg/rat/day) was given in drinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage). Results: Chronic L-NAME treatment markedly increased the mean arterial blood pressure, and co-treatment with BAY 41-2272 nearly reversed L-NAME-induced rise on mean arterial blood pressure. Non-void contractions were significantly increased in L-NAME group (0.90 ± 0.1 number/minute) compared with either DMSO or control group (0.49 ± 0.1 number/minute), which were prevented by co-treatment with BAY 41-2272 (0.56 ± 025 number/minute; p < 0.05). The threshold and peak pressure increased by 70 and 44%, respectively, after chronic L-NAME treatment, while co-treatment with BAY 41-2272 largely attenuated both effects (27 and 22% increase, respectively). The frequency of micturition cycles decreased by about of 50% in L-NAME-treated rats compared with control animals, and co-treatment with BAY 41-2272 normalized this parameter. Conclusions: Our data show that long-term oral administration of BAY 41-2272 counteracts the bladder dysfunction seen in NO-deficient rats, indicating that restoration of the NO-cGMP pathway by this compound may be of beneficial value to treat bladder symptoms.

Objetivo: avaliar os efeitos protetores do BAY 41-2272, um ativador solúvel da guanilato ciclase, sobre alteração dos parâmetros citométricos em ratos deficientes de óxido nítrico (NO). Métodos: os ratos foram divididos nos seguintes grupos: (a) controle; (b) DMSO (c) L-NAME; (d) BAY 41-2272 isolado; (e) L-NAME + BAY 41-2272. O bloqueador da NO-sintase L-NAME (20 mg/rato/dia) foi ministrado na água de beber, concomitantemente ou não com o BAY 41-2272 (10 mg/kg/dia, ministrado por gavagem). Resultados: o tratamento crônico com L-NAME aumentou de forma acentuada a pressão arterial média, e o co-tratamento com BAY 41-2272 quase reverteu o aumento na pressão arterial média induzido por L-NAME. Contrações não esvaziadoras da bexiga mostraram-se significativamente aumentadas no grupo L-NAME (0,90 ± 0,1 número/minuto) comparadas com DMSO ou grupo controle (0,49 ± 0,1 número/minuto), que foram evitadas pelo co-tratamento com BAY 41-2272 (0,56 ± 0,25 número/minuto; p < 0,05). O limiar e o pico de pressão aumentaram em 70 e 44%, respectivamente, após o tratamento crônico com L-NAME, enquanto o co-tratamento com BAY 41-2272 atenuou muito ambos os efeitos (27 e 22% de aumento, respectivamente). A frequência de ciclos de micção diminuiu em 50% nos ratos tratados com L-NAME em comparação aos animais controle; o cotratamento com BAY 41-2272 normalizou esse parâmetro. Conclusões: nossos dados mostram que a administração oral a longo prazo de BAY 41-2272 contrapõe-se à disfunção de bexiga vista em ratos deficientes de NO, o que sugere que a restauração da via da NO-cGMP por esse composto pode ter valor benéfico para tratar sintomas vesicais.

Administration of BAY 41-2272 prevents bladder dysfunction in nitric-oxide deficient rats.

OBJECTIVE: to evaluate the protective effects of BAY 41-2272, a soluble guanylate cyclase activator, on changes in cystometric parameters in rats deficient in nitric oxide (NO). METHODS: Rats were divided into the following groups: (a) control; (b) DMSO; (c) L-NAME; (d) BAY 41-2272 alone; (e) L-NAME + BAY 41-2272. The NO synthase blocker L-NAME (20 mg/rat/day) was given in drinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage). RESULTS: Chronic L-NAME treatment markedly increased the mean arterial blood pressure, and co-treatment with BAY 41-2272 nearly reversed L-NAME-induced rise on mean arterial blood pressure. Non-void contractions were significantly increased in L-NAME group (0.90 ± 0.1 number/minute) compared with either DMSO or control group (0.49 ± 0.1 number/minute), which were prevented by co-treatment with BAY 41-2272 (0.56 ± 025 number/minute; p < 0.05). The threshold and peak pressure increased by 70 and 44%, respectively, after chronic L-NAME treatment, while co-treatment with BAY 41-2272 largely attenuated both effects (27 and 22% increase, respectively). The frequency of micturition cycles decreased by about of 50% in L-NAME-treated rats compared with control animals, and co-treatment with BAY 41-2272 normalized this parameter. CONCLUSIONS: Our data show that long-term oral administration of BAY 41-2272 counteracts the bladder dysfunction seen in NO-deficient rats, indicating that restoration of the NO-cGMP pathway by this compound may be of beneficial value to treat bladder symptoms.

Arcus to arcus microsling: technique and preliminary results.

Sling procedures have been around for decades in the management of female stress urinary incontinence (SUI), but only in the past decade have they become the preferred technique. The arcus to arcus microsling is an anatomical approach that involves placing a midurethral low-tension tape anchored to the obturator internus muscles bilaterally at the level of the tendinous arc. From February 2005 to July 2006, 20 female patients (mean age=53 years old) with SUI underwent arcus to arcus microsling procedure. Of these, 18 were available for a minimum follow-up of 12 months. After 12 months, 16 (88%) patients were dry, 1 (5.5%) improved, and 1 (5.5%) was incontinent. The arcus to arcus microsling is emerging as a promising option in the management of women with SUI.