Terapia farmacológica y avances terapéuticos en xerostomía e hiposalivación / Pharmacological therapy and therapeutic advancesin xerostomy and hyposalivation

La saliva juega un rol determinante en el mantenimiento y función de los tejidos orales, donde un decremento en los niveles del flujo salival conllevan a una hiposalivación o hiposialia, trayendo consigo una serie de características que propician un ambiente ideal para la instalaciónde microorganismos oportunistas y condiciones nocivas para la saludoral y sistémica de los pacientes. Hoy en día existen múltiples causas que conllevan a una hiposialia, entre ellas el síndrome de Sjõgren, la radioterapia de haz externo, entre otras, los cuales se han puesto a prueba mediante sialogogos farmacológicos como pilocarpina, cevimelina, betanecoly carbacolina, además de alternativas terapéuticas para revertir los signos obtenidos por la hiposalivación y mitigar los síntomas de xerostomía. El objetivo del presente es realizar una revisión de literatura sobre el tratamiento farmacológico en hiposalivación y xerostomía ensíndrome de Sjõgren y radioterapia de haz externo.

Saliva plays a determinant role in the maintenance and function of oral tissues, where a decrease in salivary flow levels leads to hyposalivation or hyposialia, bringing with it a series of characteristics that provide anideal environment for the installation of opportunistic microorganisms and conditions harmful to the oral and systemic health of patients.Today there are many causes that lead to hyposialia, including Sjögren’ssyndrome, external beam radiotherapy, among others, which have beentested by pharmacological sialogogs such as pilocarpine, cevimelin, betanecol and carbacoline, in addition to therapeutic alternativesto reverse the signs obtained by hyposalivation and to mitigate the symptoms of xerostomia. The objective of the present is to make a reviewof the literature on the pharmacological treatment in hyposalivation and xerostomia in Sjögren’s syndrome and external beam radiotherapy.

Functional and biochemical characteristics of urinary bladder muscarinic receptors in long-term alloxan diabetic rats / Características funcionais e bioquímicas dos receptores muscarínicos da bexiga de ratos com diabetes crônico induzido por aloxana

Objective To re-examine the function of the urinary bladder in vivoas well as to determine the functional and biochemical characteristics of bladder muscarinic receptors in long-term alloxan-induced diabetes rats.Methods Two-month-old male Wistar rats were injected with alloxan and the animals showing blood glucose levels >300mg/dL together with age-paired untreated animals were kept for 11 months. Body weight, bladder weight, blood glucose, and urinary volume over a period of 24 hours were determined in both groups of animals. A voiding cystometry in conscious control and diabetic rats was performed to determine maximal micturition pressure, micturition contraction interval and duration as well as voided and post-voiding residual volume. In addition, concentration-response curves for bethanechol in isolated bladder strips, as well as [3H]-N methyl-scopolamine binding site characteristics in bladder homogenates were determined.Results Mean bladder weight was 162.5±21.2mg versus 290±37.9mg in control and treated animals, respectively (p<0.05). Micturition contraction amplitude (34.6±4.7mmHg versus 49.6±2.5mmHg), duration (14.5±1.7 seconds versus 23.33±4.6 seconds) and interval (87.5±17.02 seconds versus 281.11±20.24 seconds) were significantly greater in alloxan diabetic rats. Voided urine volume per micturition contraction was also significantly higher in diabetic animals. However the post-voiding residual volume was not statistically different. Bethanechol potency (EC50 3µM versus 5µM) and maximal effect (31.2±5.9g/g versus 36.1±6.8g/g) in isolated bladder strips as well as number (169±4fmol/mg versus 176±3fmol/mg protein) and affinity (0.69±0.1nM versus 0.57±0.1nM) of bladder muscarinic receptors were also not statistically different.Conclusion Bladder function in vivo is altered in chronic alloxan-induced diabetes rats without changes in functional and biochemical characteristics of bladder muscarinic receptors.

Objetivo Reestudar o funcionamento da bexiga in vivo e determinar as características funcionais e bioquímicas dos receptores muscarínicos vesicais de ratos com diabetes crônico induzido por aloxana.Métodos Ratos Wistar de dois meses de idade receberam injeção de aloxana, e os animais que apresentaram glicemia >300mg/dL foram mantidos por 11 meses junto de outros não tratados e pareados por idade. Nos dois grupos de animais, peso corpóreo, peso da bexiga, glicemia e volume urinário de 24 horas foram medidos. Em ambos os grupos, realizou-se a cistometria miccional em animais não anestesiados. Foram determinados os seguintes parâmetros: pressão máxima de micção, intervalo e contração de micção, bem como o volume de esvaziamento e o volume residual pós-miccional. Além disso, foram determinadas as curvas de concentração-resposta a betanecol em preparações isoladas de bexiga e também as características dos sítios de ligação da [3H]-N-metil-escopolamina em homogenatos de bexiga.Resultados O peso médio da bexiga foi de 162,5±21,2mg versus290±37,9mg nos animais controles e tratados, respectivamente (p<0,05). A amplitude de contração (34,6±4,7mmHg versus 49,6±2,5mmHg), a duração (14,5±1,7 segundos versus 23,33±4,6 segundos) e o intervalo (87,5±17,02 segundos versus 281,11±20,24 segundos) de micção foram significantemente maiores nos ratos tratados com aloxana. O volume de urina eliminada durante a contração miccional também foi maior nos animais diabéticos. Contudo, o volume residual pós-miccional não foi estatisticamente diferente. Não foram observadas diferenças na resposta ao betanecol (EC50 3µM versus 5µM) e no seu efeito máximo (31,2±5,9g/g versus 36,1±6,8g/g) em preparações isoladas de bexiga, bem como no número total (169±43fmol/mgversus 176±3fmol/mg) e na afinidade (0,69±0,1nMversus 0,57±0,1nM) dos receptores muscarínicos da bexiga.Conclusão O funcionamento da bexiga in vivo está alterado no diabetes crônico induzido por aloxana, porém sem alterações funcionais e bioquímicas nos receptores muscarínicos da bexiga.

Neurogenic Bladder Dysfunction Caused by Seronegative Autoimmune Autonomic Ganglionopathy

Autoimmune autonomic ganglionopathy is a form of acquired autonomic failure affecting parasympathetic, sympathetic functions, usually affecting healthy young people. The disorder affects both sympathetic and parasympathetic nervous systems, with acute onset, monophasic course, and partial recovery with relative preservation of motor and sensory function. We experienced a case of young man with acute autoimmune autonomic ganglionopathy who developed voiding difficulty, sudden blurred vision and gastrointestinal discomfort without motor or sensory dysfunction. Fever developed 5 days earlier and persisted until onset of autonomic failure. Patient complained voiding difficulty and urodynamic study revealed detrusor are flexia with failure to initiate and sustain adequate detrusor contraction. Sympathetic skin response and several autonomic function tests showed abnormalities. Intravenous immunoglobulin was applied for 5 days but symptoms persisted. Thus, 5 days of plasmapheresis treatment was followed showing improvements in most of the symptoms. However bladder dysfunction persisted at 6 months follow-up, showing partial recovery at bethanechol administration.

Malakoplakia in a healthy young female patient

Malakoplakia is a rare granulomatous disease that occurs commonly in the urinary tract and secondarily in the gastrointestinal tract. Most reported cases of malakoplakia are associated with immunosuppressive diseases or chronic prolonged illness. Here, we report a rare case of malakoplakia in a young healthy adolescent without any underlying disease. A 19-year-old female was referred to our hospital following the discovery of multiple rectal polyps with sigmoidoscopy. She had no specific past medical history but complained of recurrent abdominal pain and diarrhea for 3 months. A colonoscopy revealed diverse mucosal lesions including plaques, polyps, nodules, and mass-like lesions. Histological examination revealed a sheet of histiocytes with pathognomonic Michaelis-Gutmann bodies. We treated the patient with ciprofloxacin, the cholinergic agonist bethanechol, and a multivitamin for 6 months. A follow-up colonoscopy revealed that her condition was resolved with this course of treatment.

A pilot trial on the treatment of gastroesophageal reflux-related cough in infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheezing. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms.</p><p><b>METHODS</b>Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB.</p><p><b>RESULTS</b>Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported.</p><p><b>CONCLUSIONS</b>In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.</p>

Occurrence of Intestinal Pseudo-obstruction in a Brainstem Hemorrhage Patient

Intestinal pseudo-obstruction is a massive colonic dilation with signs and symptoms of colonic obstruction, but without a mechanical cause. A 49-year-old female patient complained of nausea, vomiting, and abdominal distension 1 month after a massive brainstem hemorrhage. No improvement was seen with conservative treatments. An extended-length rectal tube was inserted to perform glycerin enema. In addition, bethanechol (35 mg per day) was administered to stimulate colonic motility. The patient's condition gradually improved over a 2-month period without any surgical intervention. Extended length rectal tube enema and bethanechol can be used to improve intestinal pseudo-obstruction in stroke patients.

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10(-8)~10(-6) M) decreased the contractile responses induced by PE (10(-9)~10(-4) M) and Ach (10(-9)~10(-4) M) in a dose-dependent manner. Melatonin (10(-7) M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10(-7) M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10(-11)~10(-7) M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

Bethanechol chloride for the prevention of postoperative urinary retention after anal surgery under spinal anesthesia

Background: Postoperative urinary retention is a commonly encountered problem after anal surgery particularly under spinal anesthesia. Bethanchol chloride, a muscarinic cholinergic receptor agonist was used to determine whether it could prevent this problem. Methods: One hundred six patients with mean age of 37+ 9 who underwent anal surgery under spinal anesthesia from January to August 2007 were included in this nonblinded randomized prospective experimental study. Forty- six patients were given bethanechol chloride 25mg/tab 1 hour post- op then another dose after 4-6 hours. Those with the urge to void but unable to do so within the hour or had hypogastric pain (VAS > 8) were immediately catheterized and the amount drain recorded. Conclusion: Although bethanechol chloride did not completely prevent the development of postoperative urinary retention, it use was associated with reduced need for the catheterization.

The Relaxing Effect of alpha-Defensin 1 on the Adrenergic Responses of Rat Bladder

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of alpha-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of alpha-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of alpha-defensin 1, the changes of effects on PE-induced contraction by alpha-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-kappaB inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE (10(-9) ~ 10(-4) M) were significantly decreased in some concentrations of alpha-defensin 1 (5x10(-9) and 5x10(-8) M). When strips were pretreated with NF-kappaB inhibitors (PDTC and sulfasalazine; 10(-7) ~ 10(-6) M), the relaxing responses by alpha-defensin 1 pretreatment were disappeared. The present study demonstrated that alpha-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-kappaB pathway. Further studies in vivo are required to clarify whether alpha-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

Estudo prospectivo do uso do betanecol na fisiologia de glândulas salivares em pacientes irradiados em região de cabeça e pescoço / A prospective study of bethanechol in the salivary glands physiology in patient following head and neck radiotherapy

Introdução: Xerostomia e/ou hipossalivação são complicações frequentes em pacientes submetidos à radioterapia em região de cabeça e pescoço. Estes efeitos adversos aumentam o risco de cárie dentária, dificuldades em mastigar, engolir e dormir, causando impacto significativo na qualidade de vida. Objetivos: Verificar se o uso profilático do betanecol durante a Radioterapia Conformada Tridimensional (RTC3D) ou Radioterapia com Intensidade Modulada do Feixe (IMRT) em região de cabeça e pescoço, reduz a queixa de xerostomia, mantém o fluxo salivar e a função das glândulas salivares. Além disso, comparar a qualidade de vida dos pacientes irradiados com e sem o uso da medicação. Método: Foi realizado estudo prospectivo duplo-cego, avaliando 97 pacientes randomizados e alocados nos Grupos betanecol (n=48) ou placebo (n=49). Os pacientes utilizaram 25mg de betanecol ou placebo duas vezes ao dia, iniciando no primeiro dia da radioterapia e mantendo até 1 mês após o tratamento. A intensidade da xerostomia foi avaliada semanalmente, desde o início até 3 meses após o término do tratamento. Foram realizados sialometria, cintilografia das glândulas salivares e questionário de qualidade de vida da Universidade de Washington (QQV-UW) em 3 Fases: Fase 1 (previamente a radioterapia); Fase 2 (entre 30-35 Gy); Fase 3 (após 60 dias da radioterapia). Resultados: Em relação à intensidade da xerostomia, os pacientes que fizeram uso da medicação apresentaram menores queixas de boca seca durante todo o período de avaliação (p<0,001). Analisando os exames de sialometria, foi observado que tanto na Fase 2 quanto na 3, o Grupo betanecol apresentou saliva não-estimulada e estimulada significantemente maior que o placebo (p<0,05). Em relação aos resultados da cintilografia, a porcentagem média de captação da parótida e excreção da submandibular do Grupo betanecol foi significativamente maior que do Grupo placebo (p<0,05). ...

Functional, Morphologic, and Molecular Biological Changes in the Bladder of OLETF Diabetic Rats according to Duration of Diabetes Mellitus

PURPOSE: Our study was undertaken to investigate changes in the bladder according to duration of diabetes mellitus in the Otsuka Long Evans Tokushima Fatty (OLETF) rat model, which is similar to type 2 diabetes. MATERIALS AND METHODS: OLETF rats (n=14) and Long Evans Tokushima Otsuka (LETO, n=14) rats were used. LETO is a normal control of OLETF. The animals were assigned to 4 groups: L-40 group, LETO rats 40 weeks after birth (n=7); O-40 group, OLETF rats 40 weeks after birth (n=7); L-60 group, LETO rats 60 weeks after birth (n=7); and O-60 group, OLETF rats 60 weeks after birth (n=7). At 40 weeks or 60 weeks after birth, blood glucose, cystometry, bladder weight, detrusor contractility, and mRNA expression of nerve growth factor (NGF) were assessed. RESULTS: Cystometry showed that diabetic bladders had increased compliance compared with the control groups at 40 and 60 weeks, and the O-60 group had greater compliance than the O-40 group. Contractile responses to electrical stimulation, bethanecol (250microM), and ATP (10 mM) were decreased in the experimental groups compared with the control groups at 40 and 60 weeks, and the O-60 group had a lower contractile response than the O-40 group. The mRNA expression of NGF was decreased in the experimental groups compared with the control groups, and the O-60 group had lower expression than the O-40 group. Changes in NGF were identified through immunohistochemical staining. CONCLUSIONS: The degree of diabetic cystopathy in OLETF rats was changed by duration of type 2 diabetes mellitus. Our results showed that the changes in the bladder in type 2 diabetes mellitus can be identified through a new rat model.

The Effect of Bethanechol Chloride with an alpha-adrenergic Blocker in Patients with Impaired Detrusor Contractility / 대한비뇨기과학회지

PURPOSE: Bethanechol enhances detrusor contraction and alpha1-blockers reduce bladder outlet resistance. We evaluated the effects of bethanechol with doxazosin in patients with impaired detrusor contractility. MATERIALS AND METHODS: Fifty-six patients that had confirmed detrusor underactivity with at least 150ml of postvoid residual urine volume(PVR) based on a urodynamic study were enrolled. The initial dosage of bethanechol given was 75mg/day, and the dosage was gradually increased to 150mg/day if necessary. Doxazosin gastro-intestinal therapeutic system(GITS)(4mg) was also given. The effect of the treatment was evaluated by a urine flow test, the amount of PVR, and frequency of clean intermittent catheterization(CIC). RESULTS: The mean follow-up period was 6 months(range, 1 to 9 months). After treatment, the mean PVR decreased from 251.8+/-149.6ml to 136.4+/-153.2ml(p<0.001) and was less than 100ml in 22(39%) of the 38 patients that showed a decrease. The maximum flow rate(Qmax) increased from 8.7+/-4.7ml/s to 11.1+/-5.6ml/s(p=0.024) and was more than 5ml/s in 13 patients(23%). Five of the 18 patients that previously required CIC could discontinue this treatment and another nine patients showed a decrease in the frequency. The mean daily frequency of CIC was reduced from 3.2 to 1.5(p=0.004). Ten of the 12 patients that were not able to void became capable of voluntary voiding. Five patients(9%) complained of adverse reactions and four of them were taken off the medication. CONCLUSIONS: The combination therapy of bethanechol with doxazosin improved emptying ability in patients with impaired detrusor contractility.

Bethanecol chloride for treatment of clomipramine-induced orgasmic dysfunction in males

OBJETIVO: Investigar se o uso do cloridato de betanecol é uma alternativa útil no manejo clínco da disfunção orgásmica induzida pela clomipramina, relatada por até 96 % dos usuários do sexo masculino. MÉTODOS: Foram estudados 12 pacientes do sexo masculino em remissão completa de transtorno de pânico porém com queixas de disfunção orgásmica grave secundária ao uso da clomipramina. Os pacientes foram aleatoriamente distribuídos ao tratamento com cloridrato de betanecol (20 mg quando necessário) ou placebo em um estudo duplo cego "crossover" de dois períodos. RESULTADOS: Foi observado um benefício claro no período de uso da droga ativa. Não foram observados efeito placebo ou "carry-over" nos pacientes inicialmete alocados ao medicamento ativo. CONCLUSÕES: Os resultados deste estudo sugerem que o cloridato de betanecol, usado em doses únicas, 45 minutos antes da relação sexual, pode ser útil em pacientes do sexo masculino apresentado disfunção orgásmica secundária ao uso da clomipramina.

The Effects of Botulinum Toxin-A on Calcium Channel and KDR Channel of the Detrusor Muscle in Rat Bladder Body / 대한비뇨기과학회지

PURPOSE: Botulium toxin-A (BoTx A) is useful in treating detrusor-sphincter dyssynergia, detrusor hyperreflexia, and refractory overactive bladder. Only the blocking action of acetycholine (ACh) release from nerve endings is the well known aspect of the action mechanism. The aim of this study is to investigate the effects of BoTx A on the detrusor muscle itself. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 3 groups: the control group, the low dose injection group (1unit/ml of BoTx A, 0.5cc), and the high dose injection group (5units/ml of BoTx A, 0.5cc). All rats were either injected with normal saline (control group) or BoTx A (injection groups). Ten days after injection, a strip of the detrusor muscle was harvested. Contraction and relaxation responses of the strips were measured by an isometric force transducer. Contractions were induced by various concentrations of ACh, bethanechol, phenylephrine (PE), high concentrations of potassium (35, 70, 105, 140mM), tetraethylammonium (TEA, 0.1, 1, 10mM), 4-aminopyridine (4-AP, a delayed rectifier K+ antagonist, 0.1, 1, 10mM), and Bay K8644 (a L-type voltage dependent calcium channel opener, 0.1, 1, 10mM). The results were analyzed by ANOVA and the Student's t test. RESULTS: Contractions of the strips were noted when concentrations were above 1mM for TEA and above 0.1mM for 4-AP. A high dose injection as well as a low dose injection of BoTx A had no significant effects on the Ach or bethanechol-induced contractions of the strips compared to the control group. Denervation supersensitivity was not found in the injection groups after the Ach and bethanechol treatments, but the contractility was decreased in high concentrations of potassium (70, 105, 100mM), TEA (10mM), 4-AP (10mM), and Bay K8644 in both the high and low dose injection groups. There was no significant difference in the decrease of contractility between the high and low dose groups with the exception of the Bay K8644 1M treatment. CONCLUSIONS: BoTx seems to have some direct effects on decreasing the contractility of the detrusor muscle by increasing the delayed rectifier K+ channel activity and decreasing the L-type voltage dependent calcium channel activity.

Efeitos do betanecol e da cisaprida sobre os parâmetros urodinâmicos após histerectomia radical em pacientes com câncer do colo do útero / Effects of bethanecol and cisapride on the urodynamic parameters after radical hysterectomy in patients with cervical cancer

OBJETIVOS: Avaliar o efeito do betanecol e/ou da cisaprida sobre os parâmetros urodinâmicos em mulheres submetidas à histerectomia radical por câncer do colo do útero. PACIENTES E MÉTODOS: Foram randomizadas 79 pacientes nos seguintes grupos: Grupo A (n=19): receberam placebo; Grupo B (n=20): receberam betanecol na dose de 30mg/dia; Grupo C (n=20): receberam cisaprida no dose de 30mg/dia; Grupo D (n=20): associação de betanecol e cisaprida, nas mesmas doses acima. Todas as medicações foram administradas por via oral, de forma duplo-cega, durante 30 dias consecutivos, a partir do 1° dia de pósoperatório. Realizou-se estudo urodinâmico, composto de fluxometria, cistometria, perfil pressórico uretral e estudo miccional, antes da cirurgia e após 30, 90, 180 e 360 dias. RESULTADOS: Observou-se que o grupo A apresentou maiores valores da capacidade de primeiro desejo e da capacidade cistométrica máxima. Não houve diferença entre os grupos quando se avaliou a pressão do detrusor e complacência vesical, mas todos eles exibiram valores menores que aqueles no pré-operatório. A freqüência de incontinência urinária de esforço não se alterou durante o acompanhamento, em nenhum dos grupos, mesmo após 360 dias de cirurgia. A presença de contrações não-inibidas foi significativamente maior no grupo D aos 30 dias, mantendo-se semelhante em todos os grupos após. Os valores do fluxo máximo e da pressão do detrusor foram mais baixos que aqueles vistos antes da cirurgia, mas no grupo placebo foram significativamente menores em relação aos demais. O resíduo pós-miccional foi mais elevado em todos os grupos, mas com diferença significativa somente no grupo A quando comparado aos demais, e 75 por cento das pacientes com resíduo maior que 100m1 na avaliação de 180 e 360 dias pertenciam ao grupo placebo. CONCLUSÕES: O betanecol e a cisaprida, quando comparados ao placebo, determinaram menor capacidade de primeiro desejo e capacidade cistométrica máxima; não se observou diferença na pressão do detrusor, na complacência vesical, na pressão máxima de fechamento uretral e no comprimento funcional da uretra; os valores do fluxo máximo e da pressão do detrusor no fluxo máximo foram significativamente maiores, com menores resíduos pós-miccionais. A associação de betanecol e cisaprida propiciou parâmetros urodinâmicos semelhantes aos grupos que utilizaram as drogas, exceto pela maior freqüência de instabilidade do detrusor na avaliação de 30 dias...

The Effects of Pyridostigmine and Levosulpiride on the Contraction of Rabbit Urinary Bladders / 대한비뇨기과학회지

PURPOSE: This study was performed to identify the effects of bethanechol, pyridostigmine and levosulpiride, on the contraction of rabbit bladder strip tissue in a single agent administration, and to investigate the synergistic effects in a mixed administration. MATERIALS AND METHODS: Smooth muscle strips of bladder were prepared using female, New Zealand white, rabbits. After an equilibration period, dose response curves to each agent, with cumulative administration, were performed in the basal tension state of the strips. Each strip was then pretreated with the agent at the maximal concentration that would not induce a bladder contraction, and second dose-response curves for the other agents were obtained. Following this, the maximal stimulation with bethanechol was performed, and during the tonic response, pyridostigmine or levosulpiride was administrated to observe any synergistic effects of the agents. Similar experiments were repeated for the pyridostigmine and levosulpiride. RESULTS: Each agent elicited a dose-dependent contractile response, in the order; bethanechol (0-4.49g/100mg tissue), pyridostigmine (0-1.58g/100mg tissue) and levosulpiride (0-0.44g/100mg tissue). In the presence of pyridostigmine (3x10(-6)M) or levosulpiride (10(-4)M), no additive effects were noted after the cumulative stimulation with bethanechol (10(-10)-10(-4)M). During the tonic response of bethanechol (10(-4)M) or pyridostigmine (10(-2)M), the addition of levosulpiride (10(-2)M) induced a significant increase in the bladder strip contractions, but the addition of pyridostigmine (10(-2)M) or bethanechol (10(-4)M) decreased the maximal response (p<0.05). CONCLUSIONS: These results imply that pyridostigmine may be useful for impaired detrusor contractility management. Synergistic effects can also be expected when administrating levosulpiride, in addition to bethanechol, in improving bladder contractility.

Effects of Ylang-Ylang Oil on the Relaxation of Rat Bladder Muscles

PURPOSE: In cases of overactive bladders, especially hyperreflexic neurogenic bladders, that arise in patients with spine disorder above sacral micturition center, current primary treatment modalities include the administration of anticholinergics and the intermittent catheterization. Because anticholinergics have many side effects including dry mouth, the demand for new agents has been rising. This study was designed to investigate the effects of ylang-ylang (YY) essential oil, which is currently used in aromatherapy, on the relaxation of urinary bladder muscle in vitro. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a pressure transducer. Effects of YY oil were assessed on resting tension, electrical field stimulation(EFS)-, bethanechol-, ATP- and KCl-induced contraction. In order to determine the mechanism of YY oil, effects of YY oil on above all stimulations were assessed in the presence of methylene blue, L-NAME(N-nitro-L-arginine methyl ester) and N-ethylmaleimide. RESULTS: The contractility of strips pre-treated with YY oil was significantly decreased on all stimulation-induced contractions. There was no statistically significant difference between treated group only with YY oil and pre-treated group with YY oil and methylene blue. Similar findings were obtained when L-NAME(another NOS inhibitor) was used. When N-ethylmaleimide(c-AMP inhibitor) was employed, there was a statistically significant decrease in the rate of contraction induced by EFS, bethanechol, KCl and ATP applications. CONCLUSION: From the obtained data, the results of this study indicate that YY essential oil has relaxing effect on the bladder, and such mechanism is thought to be brought about by a pathway mediated by c-AMP.

Betanecol no tratamento da retençäo urinária provocada pela morfina subracnóidea / Betanecol in the treatment of spinal morphine-induced urinary retention

A morfina tem sido utilizada nos bloqueios subaracnóides para analgesia pós-operatória graças ao seu potencial analgésico prolongado e intenso. Porém, seus efeitos colaterais muitas vezes restringem seu uso. A retençäo urinária é um deles. O objetivo deste estudo foi avaliar o emprego do betanecol para tratamento da retençäo urinária causada pela morfina subaracnóidea, evitando assim a cateterizaçäo vesical do paciente. Método: De quarenta e sete pacientes que foram submetidos a procedimentos cirúrgicos com técnica anestésica de bloqueios subaracnóides nas clínicas cirúrgicas e obstétricas com administraçäo de morfina na dose de 0,1 mg, 26 pacientes apresentaram retençäo urinária (55,3 por cento). Quando o tratamento clássico (estimulaçäo miccional e compressas locais) näo evoluiu com sucesso, foram utilizadas doses fracionadas de 12,5 mg de betanecol, por via oral a cada hora, totalizando 50 mg em 4 horas. Após esse período sem resposta adequada ou se o paciente apresentasse incômodo vesical intenso antes de completar a última dose da medicaçäo, seria feita cateterizaçäo vesical ou o uso de naloxona, classificando o método como ineficaz nesses casos. Resultados: Nos pacientes que apresentaram retençäo urinária, o trtamento conservador näo obteve sucesso. Porém administrando-se betanecol de acordo com a padronizaçäo das doses nesse estudo, o mesmo foi eficaz em 14 pacientes (53,8). Conclusöes: O betanecol pode ser um bom coadjuvante no tratamento da retençäo urinária provocada pela morfina subracnóidea

Serotonin(5-HT): can it be a cause in overactive bladder

PURPOSE: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, this study examines what drugs inhibit the serotonin-induced detrusor contractions. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001-0.01mM) were assessed on resting tension. Electrical field stimulation (EFS), bethanechol (0.0001-0.01mM), ATP (1-3mM) or KCl(63.5-254mM)-induced contractions using application in organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS, bethanechol, ATP or KCl-induced contraction under serotonin (0.001mM) was assessed and serotonin (0.001 to 0.1mM) was cumulatively added to the organ bath following pre-incubation with propranolol, ketanserine, tropisetron, propiverine, sodium nitroprusside or doxazocin. RESULTS: There are two phases to the serotonin-induced responsean initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001mM serotonin (p<0.05). There was no effect on the responses to ATP, KCl, or EFS under 0.001mM serotonin. The 5-HT2 receptor is mainly responsible for serotonin-induced contractions of the detrusor (p<0.05), while the 5-HT1 receptor is partially responsible. Doxazocin and propiverine each significantly suppressed the responses to serotonin, while sodium nitroprusside and tropisetron each had no effect (p<0.05). CONCLUSIONS: Because the 5-HT2 antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT2 antagonist seems to improve lower urinary tract symptoms.

Acute Effects of Superoxides on the Relaxation of Rabbit Corporal Smooth Muscles / 대한남성과학회지

PURPOSE: In an aerobic environment, all biological organisms react with reactive oxygen specise, especially O2 free radicals and hydrogen peroxide. Although acute disorders do not appear, continuous increases of it can lead to aging or cancer. In this study, the acute effects of duroquinone (2,3,5,6-tetramethyl-1,4-benzoquinone, DQ, superoxide radical generator) on corporal smooth muscle was investigated, which causes flavorprotein to produce superoxide via chemical reduction reaction. MATERIAL AND METHOD: Under the same conditions, corporal smooth muscle strips were acquired from 2.0-2.5 kg Male New Zealand White rabbit. Then strips were placed in tension measuring apparatus. After strip was contracted by phenylephrine, an electric field stimulation (EFS)- and various drugs-induced relaxation rate was measured. Relaxation rates by above-mentioned methods were measured again following incubation of DQ or DQ and diethyldithiocarbamate (DETCA, superoxide dismutase inhibitor). The tension percentages were calculated with respect to the control group. RESULTS: The resting tension of the muscle strip was not changed by applying of DQ (0.01, 0.1 and 1 mM). The relaxation rates by EFS and bethanechol were not attenuated after DQ was incubated, but attenuated after DQ and DETCA were incubated. The relaxation rate by ATP was not attenuated after DQ, or DQ and DETCA was incubated. The relaxation rates by sodium nitroprusside was attenuated after DQ only was incubated. CONCLUSIONS: Superoxide seems to eliminate nitric oxide, and thus be an important corporal smooth muscle relaxation inhibitor.